Obesity

Researchers published the study covered in this summary on medRxiv.org as a preprint that has not yet been peer reviewed.

Key takeaways

• The study results suggest that obesity may accelerate waning of antibody response to SARS-CoV-2 vaccination and increased breakthrough infections with COVID-19.
• The findings documented evidence of reduced neutralizing antibody capacity 6 months after primary vaccination in people with severe obesity.
• This was a large study involving about more than 3.5 million people who had received at least two doses of COVID-19 vaccine, including more than 650,000 with obesity.

Why this matters

• Obesity is associated with comorbidities that independently increase the risk for severe COVID-19, including type 2 diabetes, chronic kidney disease, and heart failure.
• The authors concluded that additional or more frequent booster doses are likely to be required to maintain protection among people with obesity against COVID-19.

Study design

• Prospective longitudinal study of the incidence and severity of COVID-19 infections and immune responses in a cohort of more than 3.5 million adults from a Scottish healthcare database who received two or three doses of COVID-19 vaccine. The data came from the study, centered at the University of Edinburgh.
• About 16% had obesity with a body mass index of 30-39.9 kg/m², and an additional 3% had severe obesity with a BMI of 40 or greater.
• Although not specified in this preprint, another said that the vaccines administered in Scotland have been the Pfizer-BioNTech and Oxford-AstraZeneca formulations.

Key results

• Between Sept. 14, 2020, and March 19, 2022, 10,983 people (0.3% of the total cohort; 6.0 events per 1,000 person-years) had severe COVID-19, consisting of 9,733 who were hospitalized and 2,207 who died (957 of those hospitalized also died).
• People with obesity or severe obesity were at higher risk of hospitalization or death from COVID-19 after both a second and third (booster) dose of vaccine.
• Compared with those with normal weight, those with severe obesity (BMI higher than 40) were at significantly increased risk for severe COVID-19 after a second vaccine dose, with an adjusted rate ratio 1.76, whereas those with standard obesity (BMI, 30-40) were at a modestly but significantly increased risk with an adjusted rate ratio of 1.11.
• Breakthrough infections after the second dose for those with severe obesity, obesity, and normal weight occurred on average at 10 weeks, 15 weeks, and 20 weeks, respectively.
• Interaction testing showed that vaccine effectiveness significantly diminished over time across BMI groups, and protection waned more rapidly as BMI increased.
• Results from immunophenotyping studies run in a subgroup of several dozen subjects with severe obesity or normal weight showed significant decrements in the robustness of antibody responses in those with severe obesity 6 months after a second or third vaccine dose.

Limitations

• The authors did not specify any limitations.

Disclosures

• The study received no commercial funding.
• One author received funding from Wellcome.

This is a summary of a preprint research study , “Accelerated waning of the humoral response to SARS-CoV-2 vaccines in obesity,” published by researchers primarily at the University of Cambridge (England), on medRxiv. This study has not yet been peer reviewed. The full text of the study can be found on medRxiv.org.



A version of this article first appeared on Medscape.com.

Researchers published the study covered in this summary on medRxiv.org as a preprint that has not yet been peer reviewed.

Key takeaways

• The study results suggest that obesity may accelerate waning of antibody response to SARS-CoV-2 vaccination and increased breakthrough infections with COVID-19.
• The findings documented evidence of reduced neutralizing antibody capacity 6 months after primary vaccination in people with severe obesity.
• This was a large study involving about more than 3.5 million people who had received at least two doses of COVID-19 vaccine, including more than 650,000 with obesity.

Why this matters

• Obesity is associated with comorbidities that independently increase the risk for severe COVID-19, including type 2 diabetes, chronic kidney disease, and heart failure.
• The authors concluded that additional or more frequent booster doses are likely to be required to maintain protection among people with obesity against COVID-19.

Study design

• Prospective longitudinal study of the incidence and severity of COVID-19 infections and immune responses in a cohort of more than 3.5 million adults from a Scottish healthcare database who received two or three doses of COVID-19 vaccine. The data came from the study, centered at the University of Edinburgh.
• About 16% had obesity with a body mass index of 30-39.9 kg/m², and an additional 3% had severe obesity with a BMI of 40 or greater.
• Although not specified in this preprint, another said that the vaccines administered in Scotland have been the Pfizer-BioNTech and Oxford-AstraZeneca formulations.

Key results

• Between Sept. 14, 2020, and March 19, 2022, 10,983 people (0.3% of the total cohort; 6.0 events per 1,000 person-years) had severe COVID-19, consisting of 9,733 who were hospitalized and 2,207 who died (957 of those hospitalized also died).
• People with obesity or severe obesity were at higher risk of hospitalization or death from COVID-19 after both a second and third (booster) dose of vaccine.
• Compared with those with normal weight, those with severe obesity (BMI higher than 40) were at significantly increased risk for severe COVID-19 after a second vaccine dose, with an adjusted rate ratio 1.76, whereas those with standard obesity (BMI, 30-40) were at a modestly but significantly increased risk with an adjusted rate ratio of 1.11.
• Breakthrough infections after the second dose for those with severe obesity, obesity, and normal weight occurred on average at 10 weeks, 15 weeks, and 20 weeks, respectively.
• Interaction testing showed that vaccine effectiveness significantly diminished over time across BMI groups, and protection waned more rapidly as BMI increased.
• Results from immunophenotyping studies run in a subgroup of several dozen subjects with severe obesity or normal weight showed significant decrements in the robustness of antibody responses in those with severe obesity 6 months after a second or third vaccine dose.

Limitations

• The authors did not specify any limitations.

Disclosures

• The study received no commercial funding.
• One author received funding from Wellcome.

This is a summary of a preprint research study , “Accelerated waning of the humoral response to SARS-CoV-2 vaccines in obesity,” published by researchers primarily at the University of Cambridge (England), on medRxiv. This study has not yet been peer reviewed. The full text of the study can be found on medRxiv.org.



A version of this article first appeared on Medscape.com.

Researchers published the study covered in this summary on medRxiv.org as a preprint that has not yet been peer reviewed.

Key takeaways

• The study results suggest that obesity may accelerate waning of antibody response to SARS-CoV-2 vaccination and increased breakthrough infections with COVID-19.
• The findings documented evidence of reduced neutralizing antibody capacity 6 months after primary vaccination in people with severe obesity.
• This was a large study involving about more than 3.5 million people who had received at least two doses of COVID-19 vaccine, including more than 650,000 with obesity.

Why this matters

• Obesity is associated with comorbidities that independently increase the risk for severe COVID-19, including type 2 diabetes, chronic kidney disease, and heart failure.
• The authors concluded that additional or more frequent booster doses are likely to be required to maintain protection among people with obesity against COVID-19.

Study design

• Prospective longitudinal study of the incidence and severity of COVID-19 infections and immune responses in a cohort of more than 3.5 million adults from a Scottish healthcare database who received two or three doses of COVID-19 vaccine. The data came from the study, centered at the University of Edinburgh.
• About 16% had obesity with a body mass index of 30-39.9 kg/m², and an additional 3% had severe obesity with a BMI of 40 or greater.
• Although not specified in this preprint, another said that the vaccines administered in Scotland have been the Pfizer-BioNTech and Oxford-AstraZeneca formulations.

Key results

• Between Sept. 14, 2020, and March 19, 2022, 10,983 people (0.3% of the total cohort; 6.0 events per 1,000 person-years) had severe COVID-19, consisting of 9,733 who were hospitalized and 2,207 who died (957 of those hospitalized also died).
• People with obesity or severe obesity were at higher risk of hospitalization or death from COVID-19 after both a second and third (booster) dose of vaccine.
• Compared with those with normal weight, those with severe obesity (BMI higher than 40) were at significantly increased risk for severe COVID-19 after a second vaccine dose, with an adjusted rate ratio 1.76, whereas those with standard obesity (BMI, 30-40) were at a modestly but significantly increased risk with an adjusted rate ratio of 1.11.
• Breakthrough infections after the second dose for those with severe obesity, obesity, and normal weight occurred on average at 10 weeks, 15 weeks, and 20 weeks, respectively.
• Interaction testing showed that vaccine effectiveness significantly diminished over time across BMI groups, and protection waned more rapidly as BMI increased.
• Results from immunophenotyping studies run in a subgroup of several dozen subjects with severe obesity or normal weight showed significant decrements in the robustness of antibody responses in those with severe obesity 6 months after a second or third vaccine dose.

Limitations

• The authors did not specify any limitations.

Disclosures

• The study received no commercial funding.
• One author received funding from Wellcome.

This is a summary of a preprint research study , “Accelerated waning of the humoral response to SARS-CoV-2 vaccines in obesity,” published by researchers primarily at the University of Cambridge (England), on medRxiv. This study has not yet been peer reviewed. The full text of the study can be found on medRxiv.org.



A version of this article first appeared on Medscape.com.

Pregnant women with polycystic ovary syndrome (PCOS) appear to be at significantly increased risk of experiencing cardiac complications while hospitalized during and after delivery.

An estimated 5 million women of childbearing age in the United States have PCOS, a hormone disorder linked to infertility. PCOS is also known to contribute to the development of cardiometabolic abnormalities like high cholesterol and high blood pressure, which are associated with acute cardiovascular complications during delivery.

But a study, published online  in the Journal of the American Heart Association, found that even after accounting for pre-eclampsia, age, comorbidities, and race, PCOS was linked to a 76% increased risk for heart failure, a 79% higher risk of a weakened heart, and an 82% increased risk of having blood clots in the hours and days around giving birth in hospital settings, compared with women without PCOS.

“Perhaps women need a closer follow-up during their pregnancy,” said Erin Michos, MD, MHS, associate director of preventive cardiology at Johns Hopkins Medicine, Baltimore, and a co-author of the study. “They’re counseled about the difficulties of getting pregnant, but what about when they get pregnant?”

Hospitalizations of women with PCOS were also associated with longer stays (3 vs. 2 days) and higher costs ($4,901 vs. $3616; P < .01), compared with women without PCOS.

Over the 17-year analysis period, the number of women with PCOS rose from 569 per 100,000 deliveries to 15,349 per 100,000 deliveries. The researchers attributed the increase in part to greater awareness and diagnosis of the disorder. Dr. Michos and her colleagues used the National Inpatient Sample, managed by the Agency for Healthcare Research and Quality, to pull claims data for women who gave birth in hospitals between 2002 and 2019.
 

Solutions?

Dr. Michos said there may be more prevention work from og.gyns. to both educate patients about their heart risks during the delivery process and also to refer them to relevant cardiac specialists.

“These women may seek out a gynecologist because of the symptoms, perhaps irregular menses, but along with that should come counseling of the long-term cardiovascular complication,” Dr. Michos said. “And after a pregnancy there should be a good handoff to a primary care provider, so they get a cardiovascular assessment.”

Lifestyle management before, during, and after pregnancy can help prevent the onset of the long-term consequences of cardiac complications during delivery, according to Valerie Baker, MD, director of the division of reproductive endocrinology and infertility at Hopkins Medicine, and her colleagues in a viewpoint published in the journal Fertility and Sterility.

“Once women with PCOS are identified by screening to be at higher risk for [cardiovascular disease], the foundational approach should be lifestyle management followed by statin therapy,” Dr. Baker’s group wrote. “These interventions should include dietary management and physical activity, especially for those who are prediabetic.”

The current study came on the heels of a June 14 meta-analysis by Dr. Michos’ group that found that women with PCOS may be twice as likely as those without PCOS to have coronary artery calcification, a precursor to atherosclerosis and a sign of the early onset of cardiovascular disease.

“We shouldn’t assume that all women of reproductive age are low risk,” Dr. Michos said. “This is the window of time that we can reshape the trajectory early in life.”

The study was supported by the Amato Fund for Women’s Cardiovascular Health research at Johns Hopkins University and through grant support from the American Heart Association (940166). Dr. Michos reported advisory board participation for AstraZeneca, Amarin, Novartis, Novo Nordisk, Bayer, Boehringer Ingelheim, Esperion, and Pfizer. Study coauthor Michael Honigberg, MD, reported consulting fees from CRISPR Therapeutics, unrelated to the present work. The remaining authors have disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Pregnant women with polycystic ovary syndrome (PCOS) appear to be at significantly increased risk of experiencing cardiac complications while hospitalized during and after delivery.

An estimated 5 million women of childbearing age in the United States have PCOS, a hormone disorder linked to infertility. PCOS is also known to contribute to the development of cardiometabolic abnormalities like high cholesterol and high blood pressure, which are associated with acute cardiovascular complications during delivery.

But a study, published online  in the Journal of the American Heart Association, found that even after accounting for pre-eclampsia, age, comorbidities, and race, PCOS was linked to a 76% increased risk for heart failure, a 79% higher risk of a weakened heart, and an 82% increased risk of having blood clots in the hours and days around giving birth in hospital settings, compared with women without PCOS.

“Perhaps women need a closer follow-up during their pregnancy,” said Erin Michos, MD, MHS, associate director of preventive cardiology at Johns Hopkins Medicine, Baltimore, and a co-author of the study. “They’re counseled about the difficulties of getting pregnant, but what about when they get pregnant?”

Hospitalizations of women with PCOS were also associated with longer stays (3 vs. 2 days) and higher costs ($4,901 vs. $3616; P < .01), compared with women without PCOS.

Over the 17-year analysis period, the number of women with PCOS rose from 569 per 100,000 deliveries to 15,349 per 100,000 deliveries. The researchers attributed the increase in part to greater awareness and diagnosis of the disorder. Dr. Michos and her colleagues used the National Inpatient Sample, managed by the Agency for Healthcare Research and Quality, to pull claims data for women who gave birth in hospitals between 2002 and 2019.
 

Solutions?

Dr. Michos said there may be more prevention work from og.gyns. to both educate patients about their heart risks during the delivery process and also to refer them to relevant cardiac specialists.

“These women may seek out a gynecologist because of the symptoms, perhaps irregular menses, but along with that should come counseling of the long-term cardiovascular complication,” Dr. Michos said. “And after a pregnancy there should be a good handoff to a primary care provider, so they get a cardiovascular assessment.”

Lifestyle management before, during, and after pregnancy can help prevent the onset of the long-term consequences of cardiac complications during delivery, according to Valerie Baker, MD, director of the division of reproductive endocrinology and infertility at Hopkins Medicine, and her colleagues in a viewpoint published in the journal Fertility and Sterility.

“Once women with PCOS are identified by screening to be at higher risk for [cardiovascular disease], the foundational approach should be lifestyle management followed by statin therapy,” Dr. Baker’s group wrote. “These interventions should include dietary management and physical activity, especially for those who are prediabetic.”

The current study came on the heels of a June 14 meta-analysis by Dr. Michos’ group that found that women with PCOS may be twice as likely as those without PCOS to have coronary artery calcification, a precursor to atherosclerosis and a sign of the early onset of cardiovascular disease.

“We shouldn’t assume that all women of reproductive age are low risk,” Dr. Michos said. “This is the window of time that we can reshape the trajectory early in life.”

The study was supported by the Amato Fund for Women’s Cardiovascular Health research at Johns Hopkins University and through grant support from the American Heart Association (940166). Dr. Michos reported advisory board participation for AstraZeneca, Amarin, Novartis, Novo Nordisk, Bayer, Boehringer Ingelheim, Esperion, and Pfizer. Study coauthor Michael Honigberg, MD, reported consulting fees from CRISPR Therapeutics, unrelated to the present work. The remaining authors have disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Pregnant women with polycystic ovary syndrome (PCOS) appear to be at significantly increased risk of experiencing cardiac complications while hospitalized during and after delivery.

An estimated 5 million women of childbearing age in the United States have PCOS, a hormone disorder linked to infertility. PCOS is also known to contribute to the development of cardiometabolic abnormalities like high cholesterol and high blood pressure, which are associated with acute cardiovascular complications during delivery.

But a study, published online  in the Journal of the American Heart Association, found that even after accounting for pre-eclampsia, age, comorbidities, and race, PCOS was linked to a 76% increased risk for heart failure, a 79% higher risk of a weakened heart, and an 82% increased risk of having blood clots in the hours and days around giving birth in hospital settings, compared with women without PCOS.

“Perhaps women need a closer follow-up during their pregnancy,” said Erin Michos, MD, MHS, associate director of preventive cardiology at Johns Hopkins Medicine, Baltimore, and a co-author of the study. “They’re counseled about the difficulties of getting pregnant, but what about when they get pregnant?”

Hospitalizations of women with PCOS were also associated with longer stays (3 vs. 2 days) and higher costs ($4,901 vs. $3616; P < .01), compared with women without PCOS.

Over the 17-year analysis period, the number of women with PCOS rose from 569 per 100,000 deliveries to 15,349 per 100,000 deliveries. The researchers attributed the increase in part to greater awareness and diagnosis of the disorder. Dr. Michos and her colleagues used the National Inpatient Sample, managed by the Agency for Healthcare Research and Quality, to pull claims data for women who gave birth in hospitals between 2002 and 2019.
 

Solutions?

Dr. Michos said there may be more prevention work from og.gyns. to both educate patients about their heart risks during the delivery process and also to refer them to relevant cardiac specialists.

“These women may seek out a gynecologist because of the symptoms, perhaps irregular menses, but along with that should come counseling of the long-term cardiovascular complication,” Dr. Michos said. “And after a pregnancy there should be a good handoff to a primary care provider, so they get a cardiovascular assessment.”

Lifestyle management before, during, and after pregnancy can help prevent the onset of the long-term consequences of cardiac complications during delivery, according to Valerie Baker, MD, director of the division of reproductive endocrinology and infertility at Hopkins Medicine, and her colleagues in a viewpoint published in the journal Fertility and Sterility.

“Once women with PCOS are identified by screening to be at higher risk for [cardiovascular disease], the foundational approach should be lifestyle management followed by statin therapy,” Dr. Baker’s group wrote. “These interventions should include dietary management and physical activity, especially for those who are prediabetic.”

The current study came on the heels of a June 14 meta-analysis by Dr. Michos’ group that found that women with PCOS may be twice as likely as those without PCOS to have coronary artery calcification, a precursor to atherosclerosis and a sign of the early onset of cardiovascular disease.

“We shouldn’t assume that all women of reproductive age are low risk,” Dr. Michos said. “This is the window of time that we can reshape the trajectory early in life.”

The study was supported by the Amato Fund for Women’s Cardiovascular Health research at Johns Hopkins University and through grant support from the American Heart Association (940166). Dr. Michos reported advisory board participation for AstraZeneca, Amarin, Novartis, Novo Nordisk, Bayer, Boehringer Ingelheim, Esperion, and Pfizer. Study coauthor Michael Honigberg, MD, reported consulting fees from CRISPR Therapeutics, unrelated to the present work. The remaining authors have disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.

This transcript has been edited for clarity.

It’s important to remember and to think about the first time when patients with obesity come to see us: What have they faced? What have been their struggles? What shame and blame and bias have they faced?

One of the first things that I do when a patient comes to see me is invite them to share their weight journey with me. I ask them to tell me about their struggles, about what’s worked and what hasn’t worked, what they would like, and what their health goals are.

As they share their stories, I look for the opportunity to share with them that obesity is not their fault, but that it’s biology driving their body to carry extra weight and their body is super smart. Neither their body nor their brain want them to starve.

Our bodies evolved during a time where there was food scarcity and the potential of famine. We have a complex system that was designed to make sure that we always held on to extra weight, specifically extra fat, because that’s how we store energy. In the current obesogenic environment, what happens is our bodies carry extra weight, or specifically, extra fat.

Again, I say to them, this is biology. Your body’s doing exactly what it was designed to do. Your body’s very smart, but now we have to figure out how to help your body want to carry less fat because it is impacting your health. This is not your fault. Having obesity is not your fault any more than having diabetes or hypertension is anyone’s fault. Now it’s time for all of us to use highly effective tools that target the pathophysiology of obesity.

When a patient comes to me for weight management or to help them treat their obesity, I listen to them, and I look for clues as to what might help that specific patient. Every patient deserves to have individualized treatment. One medicine may be right for one person, another medicine may be right for another, and surgery may be right for another patient. I really try to listen and hear what that patient is telling me.

What we as providers really need is tools – different options – to be able to provide for our patients and basically present them with different options, and then guide them toward the best therapy for them. Whether it’s semaglutide or tirzepatide potentially in the future, these types of medications are excellent options for our patients. They’re highly effective tools with safe profiles.

A question that I often get from providers or patients is, “Well, Doctor, I’ve lost the weight now. How long should I take this medicine? Can I stop it now?”

Then, we have a conversation, and we actually usually have this conversation even before we start the medicine. Basically, we talk about the fact that obesity is a chronic disease. There’s no cure for obesity. Because it’s a chronic disease, we need to treat it like we would treat any other chronic disease.

The example that I often use is, if you have a patient who has hypertension and you start them on an antihypertensive medication, what happens? Their blood pressure goes down. It improves. Now, if their blood pressure is improved with a specific antihypertensive, would you stop that medicine? What would happen if you stopped that antihypertensive? Well, their blood pressure would go up, and we wouldn’t be surprised.

In the same way, if you have a patient who has obesity and you start that patient on an antiobesity medication, and their weight decreases, and their body fat mass at that point decreases, what would happen if you stop that medicine? They lost the weight, but you stop the medicine. Well, their weight gain comes back. They regain the weight.

We should not be surprised that weight gain occurs when we stop the treatment. That really underscores the fact that treatment needs to be continued. If a patient is started on an antiobesity medication and they lose weight, that medication needs to be continued to maintain that weight loss.

Basically, we eat food and our body responds by releasing these hormones. The hormones are made in our gut and in our pancreas and these hormones inform our brain. Are we hungry? Are we full? Where are we with our homeostatic set point of fat mass? Based on that, our brain is like the sensor or the thermostat.

Obesity is a chronic, treatable disease. We should treat obesity as we treat any other chronic disease, with effective and safe approaches that target underlying disease mechanisms. These results in the SURMOUNT-1 trial underscore that tirzepatide may be doing just that. Remarkably, 9 in 10 individuals with obesity lost weight while taking tirzepatide. These results are impressive. They’re an important step forward in potentially expanding effective therapeutic options for people with obesity.

Dr. Jastreboff is an associate professor of medicine and pediatrics at Yale University, New Haven, Conn., and director of weight management and obesity prevention at Yale Stress Center. She reported conducting trials with Eli Lilly, Novo Nordisk, and Rhythm Pharmaceuticals; serving on scientific advisory boards for Ely Lilly, Intellihealth, Novo Nordisk, Pfizer, Rhythm Pharmaceuticals, and WW; and consulting for Boehringer Ingelheim and Scholar Rock.

A version of this article first appeared on Medscape.com.

This transcript has been edited for clarity.

It’s important to remember and to think about the first time when patients with obesity come to see us: What have they faced? What have been their struggles? What shame and blame and bias have they faced?

One of the first things that I do when a patient comes to see me is invite them to share their weight journey with me. I ask them to tell me about their struggles, about what’s worked and what hasn’t worked, what they would like, and what their health goals are.

As they share their stories, I look for the opportunity to share with them that obesity is not their fault, but that it’s biology driving their body to carry extra weight and their body is super smart. Neither their body nor their brain want them to starve.

Our bodies evolved during a time where there was food scarcity and the potential of famine. We have a complex system that was designed to make sure that we always held on to extra weight, specifically extra fat, because that’s how we store energy. In the current obesogenic environment, what happens is our bodies carry extra weight, or specifically, extra fat.

Again, I say to them, this is biology. Your body’s doing exactly what it was designed to do. Your body’s very smart, but now we have to figure out how to help your body want to carry less fat because it is impacting your health. This is not your fault. Having obesity is not your fault any more than having diabetes or hypertension is anyone’s fault. Now it’s time for all of us to use highly effective tools that target the pathophysiology of obesity.

When a patient comes to me for weight management or to help them treat their obesity, I listen to them, and I look for clues as to what might help that specific patient. Every patient deserves to have individualized treatment. One medicine may be right for one person, another medicine may be right for another, and surgery may be right for another patient. I really try to listen and hear what that patient is telling me.

What we as providers really need is tools – different options – to be able to provide for our patients and basically present them with different options, and then guide them toward the best therapy for them. Whether it’s semaglutide or tirzepatide potentially in the future, these types of medications are excellent options for our patients. They’re highly effective tools with safe profiles.

A question that I often get from providers or patients is, “Well, Doctor, I’ve lost the weight now. How long should I take this medicine? Can I stop it now?”

Then, we have a conversation, and we actually usually have this conversation even before we start the medicine. Basically, we talk about the fact that obesity is a chronic disease. There’s no cure for obesity. Because it’s a chronic disease, we need to treat it like we would treat any other chronic disease.

The example that I often use is, if you have a patient who has hypertension and you start them on an antihypertensive medication, what happens? Their blood pressure goes down. It improves. Now, if their blood pressure is improved with a specific antihypertensive, would you stop that medicine? What would happen if you stopped that antihypertensive? Well, their blood pressure would go up, and we wouldn’t be surprised.

In the same way, if you have a patient who has obesity and you start that patient on an antiobesity medication, and their weight decreases, and their body fat mass at that point decreases, what would happen if you stop that medicine? They lost the weight, but you stop the medicine. Well, their weight gain comes back. They regain the weight.

We should not be surprised that weight gain occurs when we stop the treatment. That really underscores the fact that treatment needs to be continued. If a patient is started on an antiobesity medication and they lose weight, that medication needs to be continued to maintain that weight loss.

Basically, we eat food and our body responds by releasing these hormones. The hormones are made in our gut and in our pancreas and these hormones inform our brain. Are we hungry? Are we full? Where are we with our homeostatic set point of fat mass? Based on that, our brain is like the sensor or the thermostat.

Obesity is a chronic, treatable disease. We should treat obesity as we treat any other chronic disease, with effective and safe approaches that target underlying disease mechanisms. These results in the SURMOUNT-1 trial underscore that tirzepatide may be doing just that. Remarkably, 9 in 10 individuals with obesity lost weight while taking tirzepatide. These results are impressive. They’re an important step forward in potentially expanding effective therapeutic options for people with obesity.

Dr. Jastreboff is an associate professor of medicine and pediatrics at Yale University, New Haven, Conn., and director of weight management and obesity prevention at Yale Stress Center. She reported conducting trials with Eli Lilly, Novo Nordisk, and Rhythm Pharmaceuticals; serving on scientific advisory boards for Ely Lilly, Intellihealth, Novo Nordisk, Pfizer, Rhythm Pharmaceuticals, and WW; and consulting for Boehringer Ingelheim and Scholar Rock.

A version of this article first appeared on Medscape.com.

This transcript has been edited for clarity.

It’s important to remember and to think about the first time when patients with obesity come to see us: What have they faced? What have been their struggles? What shame and blame and bias have they faced?

One of the first things that I do when a patient comes to see me is invite them to share their weight journey with me. I ask them to tell me about their struggles, about what’s worked and what hasn’t worked, what they would like, and what their health goals are.

As they share their stories, I look for the opportunity to share with them that obesity is not their fault, but that it’s biology driving their body to carry extra weight and their body is super smart. Neither their body nor their brain want them to starve.

Our bodies evolved during a time where there was food scarcity and the potential of famine. We have a complex system that was designed to make sure that we always held on to extra weight, specifically extra fat, because that’s how we store energy. In the current obesogenic environment, what happens is our bodies carry extra weight, or specifically, extra fat.

Again, I say to them, this is biology. Your body’s doing exactly what it was designed to do. Your body’s very smart, but now we have to figure out how to help your body want to carry less fat because it is impacting your health. This is not your fault. Having obesity is not your fault any more than having diabetes or hypertension is anyone’s fault. Now it’s time for all of us to use highly effective tools that target the pathophysiology of obesity.

When a patient comes to me for weight management or to help them treat their obesity, I listen to them, and I look for clues as to what might help that specific patient. Every patient deserves to have individualized treatment. One medicine may be right for one person, another medicine may be right for another, and surgery may be right for another patient. I really try to listen and hear what that patient is telling me.

What we as providers really need is tools – different options – to be able to provide for our patients and basically present them with different options, and then guide them toward the best therapy for them. Whether it’s semaglutide or tirzepatide potentially in the future, these types of medications are excellent options for our patients. They’re highly effective tools with safe profiles.

A question that I often get from providers or patients is, “Well, Doctor, I’ve lost the weight now. How long should I take this medicine? Can I stop it now?”

Then, we have a conversation, and we actually usually have this conversation even before we start the medicine. Basically, we talk about the fact that obesity is a chronic disease. There’s no cure for obesity. Because it’s a chronic disease, we need to treat it like we would treat any other chronic disease.

The example that I often use is, if you have a patient who has hypertension and you start them on an antihypertensive medication, what happens? Their blood pressure goes down. It improves. Now, if their blood pressure is improved with a specific antihypertensive, would you stop that medicine? What would happen if you stopped that antihypertensive? Well, their blood pressure would go up, and we wouldn’t be surprised.

In the same way, if you have a patient who has obesity and you start that patient on an antiobesity medication, and their weight decreases, and their body fat mass at that point decreases, what would happen if you stop that medicine? They lost the weight, but you stop the medicine. Well, their weight gain comes back. They regain the weight.

We should not be surprised that weight gain occurs when we stop the treatment. That really underscores the fact that treatment needs to be continued. If a patient is started on an antiobesity medication and they lose weight, that medication needs to be continued to maintain that weight loss.

Basically, we eat food and our body responds by releasing these hormones. The hormones are made in our gut and in our pancreas and these hormones inform our brain. Are we hungry? Are we full? Where are we with our homeostatic set point of fat mass? Based on that, our brain is like the sensor or the thermostat.

Obesity is a chronic, treatable disease. We should treat obesity as we treat any other chronic disease, with effective and safe approaches that target underlying disease mechanisms. These results in the SURMOUNT-1 trial underscore that tirzepatide may be doing just that. Remarkably, 9 in 10 individuals with obesity lost weight while taking tirzepatide. These results are impressive. They’re an important step forward in potentially expanding effective therapeutic options for people with obesity.

Dr. Jastreboff is an associate professor of medicine and pediatrics at Yale University, New Haven, Conn., and director of weight management and obesity prevention at Yale Stress Center. She reported conducting trials with Eli Lilly, Novo Nordisk, and Rhythm Pharmaceuticals; serving on scientific advisory boards for Ely Lilly, Intellihealth, Novo Nordisk, Pfizer, Rhythm Pharmaceuticals, and WW; and consulting for Boehringer Ingelheim and Scholar Rock.

A version of this article first appeared on Medscape.com.

Patients with both inflammatory bowel disease (IBD) and obesity starting on new biologic therapies do not face an increased risk for hospitalization, IBD-related surgery, or serious infection, reveals a multicenter U.S. study published online in American Journal of Gastroenterology.

“Our findings were a bit surprising, since prior studies had suggested higher clinical disease activity and risk of flare and lower rates of endoscopic remission in obese patients treated with biologics,” Siddharth Singh, MD, MS, director of the IBD Center at the University of California, San Diego, told this news organization.

“However, in this study we focused on harder outcomes, including risk of hospitalization and surgery, and did not observe any detrimental effect,” he said.

Based on the findings, Dr. Singh believes that biologics are “completely safe and effective to use in obese patients.”

He clarified, however, that “examining the overall body of evidence, I still think obesity results in more rapid clearance of biologics, which negatively impacts the likelihood of achieving symptomatic and endoscopic remission.”

“Hence, there should be a low threshold to monitor and optimize biologic drug concentrations in obese patients. I preferentially use biologics that are dosed based on body weight in patients with class II or III obesity,” he said.
 

Research findings

Dr. Singh and colleagues write that, given that between 15% and 45% of patients with IBD are obese and a further 20%-40% are overweight, obesity is an “increasingly important consideration” in its management.

It is believed that obesity, largely via visceral adiposity, has a negative impact on IBD via increased production of adipokines, chemokines, and cytokines, such as tumor necrosis factor (TNF) alpha and interleukin-6, thus affecting treatment response as well as increasing the risk for complications and infections.

However, studies of the association between obesity and poorer treatment response, both large and small, have yielded conflicting results, potentially owing to methodological limitations.

To investigate further, Dr. Singh and colleagues gathered electronic health record data from five health systems in California on adults with IBD who were new users of TNF-alpha antagonists, or the monoclonal antibodies vedolizumab or ustekinumab, between Jan. 1, 2010, and June 30, 2017.

World Health Organization definitions were used to classify the patients as having normal BMI, overweight, or obesity, and the risk for all-cause hospitalization, IBD-related surgery, or serious infection was compared between the groups.

The team reviewed the cases of 3,038 patients with IBD, of whom 31.1% had ulcerative colitis. Among the participants, 28.2% were classified as overweight and 13.7% as obese. TNF-alpha antagonists were used by 76.3% of patients.

Patients with obesity were significantly older, were more likely to be of Hispanic ethnicity, had a higher burden of comorbidities, and were more likely to have elevated C-reactive protein levels at baseline.

However, there were no significant differences between obese and nonobese patients in terms of IBD type, class of biologic prescribed, prior surgery, or prior biologic exposure.

Within 1 year of starting a new biologic therapy, 22.9% of patients required hospitalization, whereas 3.3% required surgery and 5.8% were hospitalized with a serious infection.

Cox proportional hazard analyses showed that obesity was not associated with an increased risk for hospitalization versus normal body mass index (adjusted hazard ratio, 0.90; 95% confidence interval, 0.72-1.13), nor was it associated with IBD-related surgery (aHR, 0.62; 95% CI, 0.31-1.22) or serious infection (aHR, 1.11; 95% CI, 0.73-1.71).

The results were similar when the patients were stratified by IBD type and index biologic therapy, the researchers write.

When analyzed as a continuous variable, BMI was associated with a lower risk for hospitalization (aHR, 0.98 per 1 kg/m2; P = .044) but not with IBD-related surgery or serious infection.
 

Reassuring results for the standard of care

Discussing their findings, the authors note that “the discrepancy among studies potentially reflects the shortcomings of overall obesity measured using BMI to capture clinically meaningful adiposity.”

“A small but growing body of literature suggests visceral adipose tissue is a potentially superior prognostic measure of adiposity and better predicts adverse outcomes in IBD.”

Dr. Singh said that it would be “very interesting” to examine the relationship between visceral adiposity, as inferred from waist circumference, and IBD outcomes.

Approached for comment, Stephen B. Hanauer, MD, Clifford Joseph Barborka Professor, Northwestern University Feinberg School of Medicine, Chicago, said, “At the present time, there are no new clinical implications based on this study.”

He said in an interview that it “does not require any change in the current standard of care but rather attempts to reassure that the standard of care does not change for obese patients.”

“With that being said, the standard of care may require dosing adjustments for patients based on weight, as is already the case for infliximab/ustekinumab, and monitoring to treat to target in obese patients as well as in normal or underweight patients,” Dr. Hanauer concluded.

The study was supported by the ACG Junior Faculty Development Award and the Crohn’s and Colitis Foundation Career Development Award to Dr. Singh. Dr. Singh is supported by the National Institute of Diabetes and Digestive and Kidney Diseases and reports relationships with AbbVie, Janssen, and Pfizer. The other authors report numerous financial relationships. Dr. Hanauer reports no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Patients with both inflammatory bowel disease (IBD) and obesity starting on new biologic therapies do not face an increased risk for hospitalization, IBD-related surgery, or serious infection, reveals a multicenter U.S. study published online in American Journal of Gastroenterology.

“Our findings were a bit surprising, since prior studies had suggested higher clinical disease activity and risk of flare and lower rates of endoscopic remission in obese patients treated with biologics,” Siddharth Singh, MD, MS, director of the IBD Center at the University of California, San Diego, told this news organization.

“However, in this study we focused on harder outcomes, including risk of hospitalization and surgery, and did not observe any detrimental effect,” he said.

Based on the findings, Dr. Singh believes that biologics are “completely safe and effective to use in obese patients.”

He clarified, however, that “examining the overall body of evidence, I still think obesity results in more rapid clearance of biologics, which negatively impacts the likelihood of achieving symptomatic and endoscopic remission.”

“Hence, there should be a low threshold to monitor and optimize biologic drug concentrations in obese patients. I preferentially use biologics that are dosed based on body weight in patients with class II or III obesity,” he said.
 

Research findings

Dr. Singh and colleagues write that, given that between 15% and 45% of patients with IBD are obese and a further 20%-40% are overweight, obesity is an “increasingly important consideration” in its management.

It is believed that obesity, largely via visceral adiposity, has a negative impact on IBD via increased production of adipokines, chemokines, and cytokines, such as tumor necrosis factor (TNF) alpha and interleukin-6, thus affecting treatment response as well as increasing the risk for complications and infections.

However, studies of the association between obesity and poorer treatment response, both large and small, have yielded conflicting results, potentially owing to methodological limitations.

To investigate further, Dr. Singh and colleagues gathered electronic health record data from five health systems in California on adults with IBD who were new users of TNF-alpha antagonists, or the monoclonal antibodies vedolizumab or ustekinumab, between Jan. 1, 2010, and June 30, 2017.

World Health Organization definitions were used to classify the patients as having normal BMI, overweight, or obesity, and the risk for all-cause hospitalization, IBD-related surgery, or serious infection was compared between the groups.

The team reviewed the cases of 3,038 patients with IBD, of whom 31.1% had ulcerative colitis. Among the participants, 28.2% were classified as overweight and 13.7% as obese. TNF-alpha antagonists were used by 76.3% of patients.

Patients with obesity were significantly older, were more likely to be of Hispanic ethnicity, had a higher burden of comorbidities, and were more likely to have elevated C-reactive protein levels at baseline.

However, there were no significant differences between obese and nonobese patients in terms of IBD type, class of biologic prescribed, prior surgery, or prior biologic exposure.

Within 1 year of starting a new biologic therapy, 22.9% of patients required hospitalization, whereas 3.3% required surgery and 5.8% were hospitalized with a serious infection.

Cox proportional hazard analyses showed that obesity was not associated with an increased risk for hospitalization versus normal body mass index (adjusted hazard ratio, 0.90; 95% confidence interval, 0.72-1.13), nor was it associated with IBD-related surgery (aHR, 0.62; 95% CI, 0.31-1.22) or serious infection (aHR, 1.11; 95% CI, 0.73-1.71).

The results were similar when the patients were stratified by IBD type and index biologic therapy, the researchers write.

When analyzed as a continuous variable, BMI was associated with a lower risk for hospitalization (aHR, 0.98 per 1 kg/m2; P = .044) but not with IBD-related surgery or serious infection.
 

Reassuring results for the standard of care

Discussing their findings, the authors note that “the discrepancy among studies potentially reflects the shortcomings of overall obesity measured using BMI to capture clinically meaningful adiposity.”

“A small but growing body of literature suggests visceral adipose tissue is a potentially superior prognostic measure of adiposity and better predicts adverse outcomes in IBD.”

Dr. Singh said that it would be “very interesting” to examine the relationship between visceral adiposity, as inferred from waist circumference, and IBD outcomes.

Approached for comment, Stephen B. Hanauer, MD, Clifford Joseph Barborka Professor, Northwestern University Feinberg School of Medicine, Chicago, said, “At the present time, there are no new clinical implications based on this study.”

He said in an interview that it “does not require any change in the current standard of care but rather attempts to reassure that the standard of care does not change for obese patients.”

“With that being said, the standard of care may require dosing adjustments for patients based on weight, as is already the case for infliximab/ustekinumab, and monitoring to treat to target in obese patients as well as in normal or underweight patients,” Dr. Hanauer concluded.

The study was supported by the ACG Junior Faculty Development Award and the Crohn’s and Colitis Foundation Career Development Award to Dr. Singh. Dr. Singh is supported by the National Institute of Diabetes and Digestive and Kidney Diseases and reports relationships with AbbVie, Janssen, and Pfizer. The other authors report numerous financial relationships. Dr. Hanauer reports no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Patients with both inflammatory bowel disease (IBD) and obesity starting on new biologic therapies do not face an increased risk for hospitalization, IBD-related surgery, or serious infection, reveals a multicenter U.S. study published online in American Journal of Gastroenterology.

“Our findings were a bit surprising, since prior studies had suggested higher clinical disease activity and risk of flare and lower rates of endoscopic remission in obese patients treated with biologics,” Siddharth Singh, MD, MS, director of the IBD Center at the University of California, San Diego, told this news organization.

“However, in this study we focused on harder outcomes, including risk of hospitalization and surgery, and did not observe any detrimental effect,” he said.

Based on the findings, Dr. Singh believes that biologics are “completely safe and effective to use in obese patients.”

He clarified, however, that “examining the overall body of evidence, I still think obesity results in more rapid clearance of biologics, which negatively impacts the likelihood of achieving symptomatic and endoscopic remission.”

“Hence, there should be a low threshold to monitor and optimize biologic drug concentrations in obese patients. I preferentially use biologics that are dosed based on body weight in patients with class II or III obesity,” he said.
 

Research findings

Dr. Singh and colleagues write that, given that between 15% and 45% of patients with IBD are obese and a further 20%-40% are overweight, obesity is an “increasingly important consideration” in its management.

It is believed that obesity, largely via visceral adiposity, has a negative impact on IBD via increased production of adipokines, chemokines, and cytokines, such as tumor necrosis factor (TNF) alpha and interleukin-6, thus affecting treatment response as well as increasing the risk for complications and infections.

However, studies of the association between obesity and poorer treatment response, both large and small, have yielded conflicting results, potentially owing to methodological limitations.

To investigate further, Dr. Singh and colleagues gathered electronic health record data from five health systems in California on adults with IBD who were new users of TNF-alpha antagonists, or the monoclonal antibodies vedolizumab or ustekinumab, between Jan. 1, 2010, and June 30, 2017.

World Health Organization definitions were used to classify the patients as having normal BMI, overweight, or obesity, and the risk for all-cause hospitalization, IBD-related surgery, or serious infection was compared between the groups.

The team reviewed the cases of 3,038 patients with IBD, of whom 31.1% had ulcerative colitis. Among the participants, 28.2% were classified as overweight and 13.7% as obese. TNF-alpha antagonists were used by 76.3% of patients.

Patients with obesity were significantly older, were more likely to be of Hispanic ethnicity, had a higher burden of comorbidities, and were more likely to have elevated C-reactive protein levels at baseline.

However, there were no significant differences between obese and nonobese patients in terms of IBD type, class of biologic prescribed, prior surgery, or prior biologic exposure.

Within 1 year of starting a new biologic therapy, 22.9% of patients required hospitalization, whereas 3.3% required surgery and 5.8% were hospitalized with a serious infection.

Cox proportional hazard analyses showed that obesity was not associated with an increased risk for hospitalization versus normal body mass index (adjusted hazard ratio, 0.90; 95% confidence interval, 0.72-1.13), nor was it associated with IBD-related surgery (aHR, 0.62; 95% CI, 0.31-1.22) or serious infection (aHR, 1.11; 95% CI, 0.73-1.71).

The results were similar when the patients were stratified by IBD type and index biologic therapy, the researchers write.

When analyzed as a continuous variable, BMI was associated with a lower risk for hospitalization (aHR, 0.98 per 1 kg/m2; P = .044) but not with IBD-related surgery or serious infection.
 

Reassuring results for the standard of care

Discussing their findings, the authors note that “the discrepancy among studies potentially reflects the shortcomings of overall obesity measured using BMI to capture clinically meaningful adiposity.”

“A small but growing body of literature suggests visceral adipose tissue is a potentially superior prognostic measure of adiposity and better predicts adverse outcomes in IBD.”

Dr. Singh said that it would be “very interesting” to examine the relationship between visceral adiposity, as inferred from waist circumference, and IBD outcomes.

Approached for comment, Stephen B. Hanauer, MD, Clifford Joseph Barborka Professor, Northwestern University Feinberg School of Medicine, Chicago, said, “At the present time, there are no new clinical implications based on this study.”

He said in an interview that it “does not require any change in the current standard of care but rather attempts to reassure that the standard of care does not change for obese patients.”

“With that being said, the standard of care may require dosing adjustments for patients based on weight, as is already the case for infliximab/ustekinumab, and monitoring to treat to target in obese patients as well as in normal or underweight patients,” Dr. Hanauer concluded.

The study was supported by the ACG Junior Faculty Development Award and the Crohn’s and Colitis Foundation Career Development Award to Dr. Singh. Dr. Singh is supported by the National Institute of Diabetes and Digestive and Kidney Diseases and reports relationships with AbbVie, Janssen, and Pfizer. The other authors report numerous financial relationships. Dr. Hanauer reports no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Sleeve gastrectomy (SG) and Roux-en-Y gastric bypass (RYGB) each led to good and sustainable weight loss 10 years later, although reflux was more prevalent after SG, according to the Sleeve vs. Bypass (SLEEVEPASS) randomized clinical trial.

At 10 years, there were no statistically significant between-procedure differences in type 2 diabetes remission, dyslipidemia, or obstructive sleep apnea, but hypertension remission was greater with RYGB.

However, importantly, the cumulative incidence of Barrett’s esophagus was similar after both procedures (4%) and markedly lower than reported in previous trials (14%-17%).

To their knowledge, this is the largest randomized controlled trial with the longest follow-up comparing these two laparoscopic bariatric surgeries, Paulina Salminen, MD, PhD, and colleagues write in their study published online in JAMA Surgery.

They aimed to clarify the “controversial issues” of long-term gastroesophageal reflux disease (GERD) symptoms, endoscopic esophagitis, and Barrett’s esophagus after SG vs. RYGB.    

The findings showed that “there was no difference in the prevalence of Barrett’s esophagus, contrary to previous reports of alarming rates of Barrett’s [esophagus] after sleeve gastrectomy,” Dr. Salminen from Turku (Finland) University Hospital, told this news organization in an email.

“However, our results also show that esophagitis and GERD symptoms are significantly more prevalent after sleeve [gastrectomy], and GERD is an important factor to be considered in the preoperative assessment of bariatric surgery and procedure choice,” she said.

The takeaway is that “we have two good procedures providing good and sustainable 10-year results for both weight loss and remission of comorbidities” for severe obesity, a major health risk, Dr. Salminen summarized.
 

10-year data analysis

Long-term outcomes from randomized clinical trials of laparoscopic SG vs. RYGB are limited, and recent studies have shown a high incidence of worsening of de novo GERD, esophagitis, and Barrett’s esophagus, after laparoscopic SG, Dr. Salminen and colleagues write.

To investigate, they analyzed 10-year data from SLEEVEPASS, which had randomized 240 adult patients with severe obesity to either SG or RYGB at three hospitals in Finland during 2008-2010.

At baseline, 121 patients were randomized to SG and 119 to RYGB. They had a mean age of 48 years, a mean body mass index of 45.9 kg/m², and 70% were women.

Two patients never had the surgery, and at 10 years, 10 patients had died of causes unrelated to bariatric surgery.

At 10 years, 193 of the 288 remaining patients (85%) completed the follow-up for weight loss and other comorbidity outcomes, and 176 of 228 (77%) underwent gastroscopy.

The primary study endpoint of the trial was percent excess weight loss (%EWL). At 10 years, the median %EWL was 43.5% after SG vs. 50.7% after RYGB, with a wide range for both procedures (roughly 2%-110% excess weight loss). Mean estimate %EWL was not equivalent, with it being 8.4% in favor of RYGB.

After SG and RYGB, there were no statistically significant differences in type 2 diabetes remission (26% and 33%, respectively), dyslipidemia (19% and 35%, respectively), or obstructive sleep apnea (16% and 31%, respectively).

Hypertension remission was superior after RYGB (8% vs. 24%; P = .04).

Esophagitis was more prevalent after SG (31% vs. 7%; P < .001).
 

‘Very important study’

“This is a very important study, the first to report 10-year results of a randomized controlled trial comparing the two most frequently used bariatric operations, SG and RYGB,” Beat Peter Müller, MD, MBA, and Adrian Billeter, MD, PhD, who were not involved with this research, told this news organization in an email.

“The results will have a major impact on the future of bariatric surgery,” according to Dr. Müller and Dr. Billeter, from Heidelberg (Germany) University.

The most relevant findings are the GERD outcomes, they said. Because of the high rate of upper endoscopies at 10 years (73%), the study allowed a good assessment of this.

“While this study confirms that SG is a GERD-prone procedure, it clearly demonstrates that GERD after SG does not induce severe esophagitis and Barrett’s esophagus,” they said.

Most importantly, the rate of Barrett’s esophagus, the precursor lesion of adenocarcinomas of the esophago-gastric junction is similar (4%) after both operations and there was no dysplasia in either group, they stressed.

“The main problem after SG remains new-onset GERD, for which still no predictive parameter exists,” according to Dr. Müller and Dr. Billeter.

“The take home message … is that GERD after SG is generally mild and the risk of Barrett’s esophagus is equally higher after SG and RYGB,” they said. “Therefore, all patients after any bariatric operations should undergo regular upper endoscopies.” 

However, “RYGB still leads to an increase in proton-pump inhibitor use, despite RYGB being one of the most effective antireflux procedures,” they said. “This finding needs further investigation.”

Furthermore, “a 4% Barrett esophagus rate 10 years after RYGB is troublesome, and the reasons should be investigated,” they added.

“Another relevant finding is that after 10 years, RYGB has a statistically better weight loss, which reaches the primary endpoint of the SLEEVEPASS trial for the first time,” they noted, yet the clinical relevance of this is not clear, since there was no difference in resolution of comorbidities, except for hypertension. 

Gyanprakash A. Ketwaroo, MD, of Baylor College of Medicine, Houston, who was not involved with this research, agreed that “the study shows durable and good weight loss for either type of laparoscopic surgery with important metabolic effects and confirms the long-term benefits of weight-loss surgery.”

“What is somewhat new is the lower levels of Barrett’s esophagus after sleeve gastrectomy compared with several earlier studies,” he told this news organization in an email.

“This is somewhat incongruent with the relatively high incidence of postsleeve esophagitis noted in the study, which is an accepted risk factor for Barrett’s esophagus,” he continued. “Thus, I believe concern will still remain about GERD-related complications, including Barrett’s [esophagus], after sleeve gastrectomy.”    

“This paper highlights the need for larger prospective studies, especially those that include diverse, older populations with multiple risk factors for Barrett’s esophagus,” Dr. Ketwaroo said.
 

Looking ahead

Using a large data set, such as that from SLEEVEPASS and possibly with data from the SM-BOSS trial and the BariSurg trial, with machine learning and other sophisticated analyses might identify parameters that could be used to choose the best operation for an individual patient, Dr. Salminen speculated. 

“I think what we have learned from these long-term follow-up results is that GERD assessment should be a part of the preoperative assessment, and for patients who have preoperative GERD symptoms and GERD-related endoscopic findings (e.g., hiatal hernia), gastric bypass would be a more optimal procedure choice, if there are no contraindications for it,” she said.

Patient discussions should also cover “long-term symptoms, for example, abdominal pain after RYGB,” she added.

“I am looking forward to our future 20-year follow-up results,” Dr. Salminen said, “which will shed more light on this topic of postoperative [endoscopic] surveillance.

In the meantime, “preoperative gastroscopy is necessary and beneficial, at least when considering sleeve gastrectomy,” she said.

The SLEEVEPASS trial was supported by the Mary and Georg C. Ehrnrooth Foundation, the Government Research Foundation (in a grant awarded to Turku University Hospital), the Orion Research Foundation, the Paulo Foundation, and the Gastroenterological Research Foundation. Dr. Salminen reported receiving grants from the Government Research Foundation awarded to Turku University Hospital and the Mary and Georg C. Ehrnrooth Foundation. Another coauthor received grants from the Orion Research Foundation, the Paulo Foundation, and the Gastroenterological Research Foundation during the study. No other disclosures were reported.

A version of this article first appeared on Medscape.com.

Sleeve gastrectomy (SG) and Roux-en-Y gastric bypass (RYGB) each led to good and sustainable weight loss 10 years later, although reflux was more prevalent after SG, according to the Sleeve vs. Bypass (SLEEVEPASS) randomized clinical trial.

At 10 years, there were no statistically significant between-procedure differences in type 2 diabetes remission, dyslipidemia, or obstructive sleep apnea, but hypertension remission was greater with RYGB.

However, importantly, the cumulative incidence of Barrett’s esophagus was similar after both procedures (4%) and markedly lower than reported in previous trials (14%-17%).

To their knowledge, this is the largest randomized controlled trial with the longest follow-up comparing these two laparoscopic bariatric surgeries, Paulina Salminen, MD, PhD, and colleagues write in their study published online in JAMA Surgery.

They aimed to clarify the “controversial issues” of long-term gastroesophageal reflux disease (GERD) symptoms, endoscopic esophagitis, and Barrett’s esophagus after SG vs. RYGB.    

The findings showed that “there was no difference in the prevalence of Barrett’s esophagus, contrary to previous reports of alarming rates of Barrett’s [esophagus] after sleeve gastrectomy,” Dr. Salminen from Turku (Finland) University Hospital, told this news organization in an email.

“However, our results also show that esophagitis and GERD symptoms are significantly more prevalent after sleeve [gastrectomy], and GERD is an important factor to be considered in the preoperative assessment of bariatric surgery and procedure choice,” she said.

The takeaway is that “we have two good procedures providing good and sustainable 10-year results for both weight loss and remission of comorbidities” for severe obesity, a major health risk, Dr. Salminen summarized.
 

10-year data analysis

Long-term outcomes from randomized clinical trials of laparoscopic SG vs. RYGB are limited, and recent studies have shown a high incidence of worsening of de novo GERD, esophagitis, and Barrett’s esophagus, after laparoscopic SG, Dr. Salminen and colleagues write.

To investigate, they analyzed 10-year data from SLEEVEPASS, which had randomized 240 adult patients with severe obesity to either SG or RYGB at three hospitals in Finland during 2008-2010.

At baseline, 121 patients were randomized to SG and 119 to RYGB. They had a mean age of 48 years, a mean body mass index of 45.9 kg/m², and 70% were women.

Two patients never had the surgery, and at 10 years, 10 patients had died of causes unrelated to bariatric surgery.

At 10 years, 193 of the 288 remaining patients (85%) completed the follow-up for weight loss and other comorbidity outcomes, and 176 of 228 (77%) underwent gastroscopy.

The primary study endpoint of the trial was percent excess weight loss (%EWL). At 10 years, the median %EWL was 43.5% after SG vs. 50.7% after RYGB, with a wide range for both procedures (roughly 2%-110% excess weight loss). Mean estimate %EWL was not equivalent, with it being 8.4% in favor of RYGB.

After SG and RYGB, there were no statistically significant differences in type 2 diabetes remission (26% and 33%, respectively), dyslipidemia (19% and 35%, respectively), or obstructive sleep apnea (16% and 31%, respectively).

Hypertension remission was superior after RYGB (8% vs. 24%; P = .04).

Esophagitis was more prevalent after SG (31% vs. 7%; P < .001).
 

‘Very important study’

“This is a very important study, the first to report 10-year results of a randomized controlled trial comparing the two most frequently used bariatric operations, SG and RYGB,” Beat Peter Müller, MD, MBA, and Adrian Billeter, MD, PhD, who were not involved with this research, told this news organization in an email.

“The results will have a major impact on the future of bariatric surgery,” according to Dr. Müller and Dr. Billeter, from Heidelberg (Germany) University.

The most relevant findings are the GERD outcomes, they said. Because of the high rate of upper endoscopies at 10 years (73%), the study allowed a good assessment of this.

“While this study confirms that SG is a GERD-prone procedure, it clearly demonstrates that GERD after SG does not induce severe esophagitis and Barrett’s esophagus,” they said.

Most importantly, the rate of Barrett’s esophagus, the precursor lesion of adenocarcinomas of the esophago-gastric junction is similar (4%) after both operations and there was no dysplasia in either group, they stressed.

“The main problem after SG remains new-onset GERD, for which still no predictive parameter exists,” according to Dr. Müller and Dr. Billeter.

“The take home message … is that GERD after SG is generally mild and the risk of Barrett’s esophagus is equally higher after SG and RYGB,” they said. “Therefore, all patients after any bariatric operations should undergo regular upper endoscopies.” 

However, “RYGB still leads to an increase in proton-pump inhibitor use, despite RYGB being one of the most effective antireflux procedures,” they said. “This finding needs further investigation.”

Furthermore, “a 4% Barrett esophagus rate 10 years after RYGB is troublesome, and the reasons should be investigated,” they added.

“Another relevant finding is that after 10 years, RYGB has a statistically better weight loss, which reaches the primary endpoint of the SLEEVEPASS trial for the first time,” they noted, yet the clinical relevance of this is not clear, since there was no difference in resolution of comorbidities, except for hypertension. 

Gyanprakash A. Ketwaroo, MD, of Baylor College of Medicine, Houston, who was not involved with this research, agreed that “the study shows durable and good weight loss for either type of laparoscopic surgery with important metabolic effects and confirms the long-term benefits of weight-loss surgery.”

“What is somewhat new is the lower levels of Barrett’s esophagus after sleeve gastrectomy compared with several earlier studies,” he told this news organization in an email.

“This is somewhat incongruent with the relatively high incidence of postsleeve esophagitis noted in the study, which is an accepted risk factor for Barrett’s esophagus,” he continued. “Thus, I believe concern will still remain about GERD-related complications, including Barrett’s [esophagus], after sleeve gastrectomy.”    

“This paper highlights the need for larger prospective studies, especially those that include diverse, older populations with multiple risk factors for Barrett’s esophagus,” Dr. Ketwaroo said.
 

Looking ahead

Using a large data set, such as that from SLEEVEPASS and possibly with data from the SM-BOSS trial and the BariSurg trial, with machine learning and other sophisticated analyses might identify parameters that could be used to choose the best operation for an individual patient, Dr. Salminen speculated. 

“I think what we have learned from these long-term follow-up results is that GERD assessment should be a part of the preoperative assessment, and for patients who have preoperative GERD symptoms and GERD-related endoscopic findings (e.g., hiatal hernia), gastric bypass would be a more optimal procedure choice, if there are no contraindications for it,” she said.

Patient discussions should also cover “long-term symptoms, for example, abdominal pain after RYGB,” she added.

“I am looking forward to our future 20-year follow-up results,” Dr. Salminen said, “which will shed more light on this topic of postoperative [endoscopic] surveillance.

In the meantime, “preoperative gastroscopy is necessary and beneficial, at least when considering sleeve gastrectomy,” she said.

The SLEEVEPASS trial was supported by the Mary and Georg C. Ehrnrooth Foundation, the Government Research Foundation (in a grant awarded to Turku University Hospital), the Orion Research Foundation, the Paulo Foundation, and the Gastroenterological Research Foundation. Dr. Salminen reported receiving grants from the Government Research Foundation awarded to Turku University Hospital and the Mary and Georg C. Ehrnrooth Foundation. Another coauthor received grants from the Orion Research Foundation, the Paulo Foundation, and the Gastroenterological Research Foundation during the study. No other disclosures were reported.

A version of this article first appeared on Medscape.com.

Sleeve gastrectomy (SG) and Roux-en-Y gastric bypass (RYGB) each led to good and sustainable weight loss 10 years later, although reflux was more prevalent after SG, according to the Sleeve vs. Bypass (SLEEVEPASS) randomized clinical trial.

At 10 years, there were no statistically significant between-procedure differences in type 2 diabetes remission, dyslipidemia, or obstructive sleep apnea, but hypertension remission was greater with RYGB.

However, importantly, the cumulative incidence of Barrett’s esophagus was similar after both procedures (4%) and markedly lower than reported in previous trials (14%-17%).

To their knowledge, this is the largest randomized controlled trial with the longest follow-up comparing these two laparoscopic bariatric surgeries, Paulina Salminen, MD, PhD, and colleagues write in their study published online in JAMA Surgery.

They aimed to clarify the “controversial issues” of long-term gastroesophageal reflux disease (GERD) symptoms, endoscopic esophagitis, and Barrett’s esophagus after SG vs. RYGB.    

The findings showed that “there was no difference in the prevalence of Barrett’s esophagus, contrary to previous reports of alarming rates of Barrett’s [esophagus] after sleeve gastrectomy,” Dr. Salminen from Turku (Finland) University Hospital, told this news organization in an email.

“However, our results also show that esophagitis and GERD symptoms are significantly more prevalent after sleeve [gastrectomy], and GERD is an important factor to be considered in the preoperative assessment of bariatric surgery and procedure choice,” she said.

The takeaway is that “we have two good procedures providing good and sustainable 10-year results for both weight loss and remission of comorbidities” for severe obesity, a major health risk, Dr. Salminen summarized.
 

10-year data analysis

Long-term outcomes from randomized clinical trials of laparoscopic SG vs. RYGB are limited, and recent studies have shown a high incidence of worsening of de novo GERD, esophagitis, and Barrett’s esophagus, after laparoscopic SG, Dr. Salminen and colleagues write.

To investigate, they analyzed 10-year data from SLEEVEPASS, which had randomized 240 adult patients with severe obesity to either SG or RYGB at three hospitals in Finland during 2008-2010.

At baseline, 121 patients were randomized to SG and 119 to RYGB. They had a mean age of 48 years, a mean body mass index of 45.9 kg/m², and 70% were women.

Two patients never had the surgery, and at 10 years, 10 patients had died of causes unrelated to bariatric surgery.

At 10 years, 193 of the 288 remaining patients (85%) completed the follow-up for weight loss and other comorbidity outcomes, and 176 of 228 (77%) underwent gastroscopy.

The primary study endpoint of the trial was percent excess weight loss (%EWL). At 10 years, the median %EWL was 43.5% after SG vs. 50.7% after RYGB, with a wide range for both procedures (roughly 2%-110% excess weight loss). Mean estimate %EWL was not equivalent, with it being 8.4% in favor of RYGB.

After SG and RYGB, there were no statistically significant differences in type 2 diabetes remission (26% and 33%, respectively), dyslipidemia (19% and 35%, respectively), or obstructive sleep apnea (16% and 31%, respectively).

Hypertension remission was superior after RYGB (8% vs. 24%; P = .04).

Esophagitis was more prevalent after SG (31% vs. 7%; P < .001).
 

‘Very important study’

“This is a very important study, the first to report 10-year results of a randomized controlled trial comparing the two most frequently used bariatric operations, SG and RYGB,” Beat Peter Müller, MD, MBA, and Adrian Billeter, MD, PhD, who were not involved with this research, told this news organization in an email.

“The results will have a major impact on the future of bariatric surgery,” according to Dr. Müller and Dr. Billeter, from Heidelberg (Germany) University.

The most relevant findings are the GERD outcomes, they said. Because of the high rate of upper endoscopies at 10 years (73%), the study allowed a good assessment of this.

“While this study confirms that SG is a GERD-prone procedure, it clearly demonstrates that GERD after SG does not induce severe esophagitis and Barrett’s esophagus,” they said.

Most importantly, the rate of Barrett’s esophagus, the precursor lesion of adenocarcinomas of the esophago-gastric junction is similar (4%) after both operations and there was no dysplasia in either group, they stressed.

“The main problem after SG remains new-onset GERD, for which still no predictive parameter exists,” according to Dr. Müller and Dr. Billeter.

“The take home message … is that GERD after SG is generally mild and the risk of Barrett’s esophagus is equally higher after SG and RYGB,” they said. “Therefore, all patients after any bariatric operations should undergo regular upper endoscopies.” 

However, “RYGB still leads to an increase in proton-pump inhibitor use, despite RYGB being one of the most effective antireflux procedures,” they said. “This finding needs further investigation.”

Furthermore, “a 4% Barrett esophagus rate 10 years after RYGB is troublesome, and the reasons should be investigated,” they added.

“Another relevant finding is that after 10 years, RYGB has a statistically better weight loss, which reaches the primary endpoint of the SLEEVEPASS trial for the first time,” they noted, yet the clinical relevance of this is not clear, since there was no difference in resolution of comorbidities, except for hypertension. 

Gyanprakash A. Ketwaroo, MD, of Baylor College of Medicine, Houston, who was not involved with this research, agreed that “the study shows durable and good weight loss for either type of laparoscopic surgery with important metabolic effects and confirms the long-term benefits of weight-loss surgery.”

“What is somewhat new is the lower levels of Barrett’s esophagus after sleeve gastrectomy compared with several earlier studies,” he told this news organization in an email.

“This is somewhat incongruent with the relatively high incidence of postsleeve esophagitis noted in the study, which is an accepted risk factor for Barrett’s esophagus,” he continued. “Thus, I believe concern will still remain about GERD-related complications, including Barrett’s [esophagus], after sleeve gastrectomy.”    

“This paper highlights the need for larger prospective studies, especially those that include diverse, older populations with multiple risk factors for Barrett’s esophagus,” Dr. Ketwaroo said.
 

Looking ahead

Using a large data set, such as that from SLEEVEPASS and possibly with data from the SM-BOSS trial and the BariSurg trial, with machine learning and other sophisticated analyses might identify parameters that could be used to choose the best operation for an individual patient, Dr. Salminen speculated. 

“I think what we have learned from these long-term follow-up results is that GERD assessment should be a part of the preoperative assessment, and for patients who have preoperative GERD symptoms and GERD-related endoscopic findings (e.g., hiatal hernia), gastric bypass would be a more optimal procedure choice, if there are no contraindications for it,” she said.

Patient discussions should also cover “long-term symptoms, for example, abdominal pain after RYGB,” she added.

“I am looking forward to our future 20-year follow-up results,” Dr. Salminen said, “which will shed more light on this topic of postoperative [endoscopic] surveillance.

In the meantime, “preoperative gastroscopy is necessary and beneficial, at least when considering sleeve gastrectomy,” she said.

The SLEEVEPASS trial was supported by the Mary and Georg C. Ehrnrooth Foundation, the Government Research Foundation (in a grant awarded to Turku University Hospital), the Orion Research Foundation, the Paulo Foundation, and the Gastroenterological Research Foundation. Dr. Salminen reported receiving grants from the Government Research Foundation awarded to Turku University Hospital and the Mary and Georg C. Ehrnrooth Foundation. Another coauthor received grants from the Orion Research Foundation, the Paulo Foundation, and the Gastroenterological Research Foundation during the study. No other disclosures were reported.

A version of this article first appeared on Medscape.com.

Wireless devices, like smart phones and tablets, appear to induce compulsive or even addictive use in many individuals, leading to adverse health consequences that are likely to be curtailed only through often difficult behavior modification, according to a pediatric endocrinologist’s take on the problem.

While the summary was based in part on the analysis of 234 published papers drawn from the medical literature, the lead author, Nidhi Gupta, MD, said the data reinforce her own clinical experience.

Lisa Nainggolin/MDedge News

“As a pediatric endocrinologist, the trend in smartphone-associated health disorders, such as obesity, sleep, and behavior issues, worries me,” Dr. Gupta, director of KAP Pediatric Endocrinology, Nashville, Tenn., said at the annual meeting of the Endocrine Society.

Based on her search of the medical literature, the available data raise concern. In one study she cited, for example, each hour per day of screen time was found to translate into a body mass index increase of 0.5 to 0.7 kg/m² (P < .001).

With this type of progressive rise in BMI comes prediabetes, dyslipidemia, and other metabolic disorders associated with major health risks, including cardiovascular disease. And there are others. Dr. Gupta cited data suggesting screen time before bed disturbs sleep, which has its own set of health risks.

“When I say health, it includes physical health, mental health, and emotional health,” said Dr. Gupta.

In the U.S. and other countries with a growing obesity epidemic, lack of physical activity and unhealthy eating are widely considered the major culprits. Excessive screen time contributes to both.

“When we are engaged with our devices, we are often snacking subconsciously and not very mindful that we are making unhealthy choices,” Dr. Gupta said.

The problem is that there is a vicious circle. Compulsive use of devices follows the same loop as other types of addictive behaviors, according to Dr. Gupta. She traced overuse of wireless devices to the dopaminergic system, which is a powerful neuroendocrine-mediated process of craving, response, and reward.

Like fat, sugar, and salt, which provoke a neuroendocrine reward signal, the chimes and buzzes of a cell phone provide their own cues for reward in the form of a dopamine surge. As a result, these become the “triggers of an irresistible and irrational urge to check our device that makes the dopamine go high in our brain,” Dr. Gupta explained.

Although the vicious cycle can be thwarted by turning off the device, Dr. Gupta characterized this as “impractical” when smartphones are so vital to daily communication. Rather, Dr. Gupta advocated a program of moderation, reserving the phone for useful tasks without succumbing to the siren song of apps that waste time.

The most conspicuous culprit is social media, which Dr. Gupta considers to be among the most Pavlovian triggers of cell phone addiction. However, she acknowledged that participation in social media has its justifications.

“I, myself, use social media for my own branding and marketing,” Dr. Gupta said.

The problem that users have is distinguishing between screen time that does and does not have value, according to Dr. Gupta. She indicated that many of those overusing their smart devices are being driven by the dopaminergic reward system, which is generally divorced from the real goals of life, such as personal satisfaction and activity that is rewarding monetarily or in other ways.

“I am not asking for these devices to be thrown out the window. I am advocating for moderation, balance, and real-life engagement,” Dr. Gupta said at the meeting, held in Atlanta and virtually.

She outlined a long list of practical suggestions, including turning off the alarms, chimes, and messages that engage the user into the vicious dopaminergic-reward system loop. She suggested mindfulness so that the user can distinguish between valuable device use and activity that is simply procrastination.

“The devices are designed to be addictive. They are designed to manipulate our brain,” she said. “Eliminate the reward. Let’s try to make our devices boring, unappealing, or enticing so that they only work as tools.”

The medical literature is filled with data that support the potential harms of excessive screen use, leading many others to make some of the same points. In 2017, Thomas N. Robinson, MD, professor of child health at Stanford (Calif.) University, reviewed data showing an association between screen media exposure and obesity in children and adolescents.

“This is an area crying out for more research,” Dr. Robinson said in an interview. The problem of screen time, sedentary behavior, and weight gain has been an issue since the television was invented, which was the point he made in his 2017 paper, but he agreed that the problem is only getting worse.

“Digital technology has become ubiquitous, touching nearly every aspect of people’s lives,” he said. Yet, as evidence grows that overuse of this technology can be harmful, it is creating a problem without a clear solution.

“There are few data about the efficacy of specific strategies to reduce harmful impacts of digital screen use,” he said.

While some of the solutions that Dr. Gupta described make sense, they are more easily described than executed. The dopaminergic reward system is strong and largely experienced subconsciously. Recruiting patients to recognize that dopaminergic rewards are not rewards in any true sense is already a challenge. Enlisting patients to take the difficult steps to avoid the behavioral cues might be even more difficult.

Dr. Gupta and Dr. Robinson report no potential conflicts of interest.

Wireless devices, like smart phones and tablets, appear to induce compulsive or even addictive use in many individuals, leading to adverse health consequences that are likely to be curtailed only through often difficult behavior modification, according to a pediatric endocrinologist’s take on the problem.

While the summary was based in part on the analysis of 234 published papers drawn from the medical literature, the lead author, Nidhi Gupta, MD, said the data reinforce her own clinical experience.

Lisa Nainggolin/MDedge News

“As a pediatric endocrinologist, the trend in smartphone-associated health disorders, such as obesity, sleep, and behavior issues, worries me,” Dr. Gupta, director of KAP Pediatric Endocrinology, Nashville, Tenn., said at the annual meeting of the Endocrine Society.

Based on her search of the medical literature, the available data raise concern. In one study she cited, for example, each hour per day of screen time was found to translate into a body mass index increase of 0.5 to 0.7 kg/m² (P < .001).

With this type of progressive rise in BMI comes prediabetes, dyslipidemia, and other metabolic disorders associated with major health risks, including cardiovascular disease. And there are others. Dr. Gupta cited data suggesting screen time before bed disturbs sleep, which has its own set of health risks.

“When I say health, it includes physical health, mental health, and emotional health,” said Dr. Gupta.

In the U.S. and other countries with a growing obesity epidemic, lack of physical activity and unhealthy eating are widely considered the major culprits. Excessive screen time contributes to both.

“When we are engaged with our devices, we are often snacking subconsciously and not very mindful that we are making unhealthy choices,” Dr. Gupta said.

The problem is that there is a vicious circle. Compulsive use of devices follows the same loop as other types of addictive behaviors, according to Dr. Gupta. She traced overuse of wireless devices to the dopaminergic system, which is a powerful neuroendocrine-mediated process of craving, response, and reward.

Like fat, sugar, and salt, which provoke a neuroendocrine reward signal, the chimes and buzzes of a cell phone provide their own cues for reward in the form of a dopamine surge. As a result, these become the “triggers of an irresistible and irrational urge to check our device that makes the dopamine go high in our brain,” Dr. Gupta explained.

Although the vicious cycle can be thwarted by turning off the device, Dr. Gupta characterized this as “impractical” when smartphones are so vital to daily communication. Rather, Dr. Gupta advocated a program of moderation, reserving the phone for useful tasks without succumbing to the siren song of apps that waste time.

The most conspicuous culprit is social media, which Dr. Gupta considers to be among the most Pavlovian triggers of cell phone addiction. However, she acknowledged that participation in social media has its justifications.

“I, myself, use social media for my own branding and marketing,” Dr. Gupta said.

The problem that users have is distinguishing between screen time that does and does not have value, according to Dr. Gupta. She indicated that many of those overusing their smart devices are being driven by the dopaminergic reward system, which is generally divorced from the real goals of life, such as personal satisfaction and activity that is rewarding monetarily or in other ways.

“I am not asking for these devices to be thrown out the window. I am advocating for moderation, balance, and real-life engagement,” Dr. Gupta said at the meeting, held in Atlanta and virtually.

She outlined a long list of practical suggestions, including turning off the alarms, chimes, and messages that engage the user into the vicious dopaminergic-reward system loop. She suggested mindfulness so that the user can distinguish between valuable device use and activity that is simply procrastination.

“The devices are designed to be addictive. They are designed to manipulate our brain,” she said. “Eliminate the reward. Let’s try to make our devices boring, unappealing, or enticing so that they only work as tools.”

The medical literature is filled with data that support the potential harms of excessive screen use, leading many others to make some of the same points. In 2017, Thomas N. Robinson, MD, professor of child health at Stanford (Calif.) University, reviewed data showing an association between screen media exposure and obesity in children and adolescents.

“This is an area crying out for more research,” Dr. Robinson said in an interview. The problem of screen time, sedentary behavior, and weight gain has been an issue since the television was invented, which was the point he made in his 2017 paper, but he agreed that the problem is only getting worse.

“Digital technology has become ubiquitous, touching nearly every aspect of people’s lives,” he said. Yet, as evidence grows that overuse of this technology can be harmful, it is creating a problem without a clear solution.

“There are few data about the efficacy of specific strategies to reduce harmful impacts of digital screen use,” he said.

While some of the solutions that Dr. Gupta described make sense, they are more easily described than executed. The dopaminergic reward system is strong and largely experienced subconsciously. Recruiting patients to recognize that dopaminergic rewards are not rewards in any true sense is already a challenge. Enlisting patients to take the difficult steps to avoid the behavioral cues might be even more difficult.

Dr. Gupta and Dr. Robinson report no potential conflicts of interest.

Wireless devices, like smart phones and tablets, appear to induce compulsive or even addictive use in many individuals, leading to adverse health consequences that are likely to be curtailed only through often difficult behavior modification, according to a pediatric endocrinologist’s take on the problem.

While the summary was based in part on the analysis of 234 published papers drawn from the medical literature, the lead author, Nidhi Gupta, MD, said the data reinforce her own clinical experience.

Lisa Nainggolin/MDedge News

“As a pediatric endocrinologist, the trend in smartphone-associated health disorders, such as obesity, sleep, and behavior issues, worries me,” Dr. Gupta, director of KAP Pediatric Endocrinology, Nashville, Tenn., said at the annual meeting of the Endocrine Society.

Based on her search of the medical literature, the available data raise concern. In one study she cited, for example, each hour per day of screen time was found to translate into a body mass index increase of 0.5 to 0.7 kg/m² (P < .001).

With this type of progressive rise in BMI comes prediabetes, dyslipidemia, and other metabolic disorders associated with major health risks, including cardiovascular disease. And there are others. Dr. Gupta cited data suggesting screen time before bed disturbs sleep, which has its own set of health risks.

“When I say health, it includes physical health, mental health, and emotional health,” said Dr. Gupta.

In the U.S. and other countries with a growing obesity epidemic, lack of physical activity and unhealthy eating are widely considered the major culprits. Excessive screen time contributes to both.

“When we are engaged with our devices, we are often snacking subconsciously and not very mindful that we are making unhealthy choices,” Dr. Gupta said.

The problem is that there is a vicious circle. Compulsive use of devices follows the same loop as other types of addictive behaviors, according to Dr. Gupta. She traced overuse of wireless devices to the dopaminergic system, which is a powerful neuroendocrine-mediated process of craving, response, and reward.

Like fat, sugar, and salt, which provoke a neuroendocrine reward signal, the chimes and buzzes of a cell phone provide their own cues for reward in the form of a dopamine surge. As a result, these become the “triggers of an irresistible and irrational urge to check our device that makes the dopamine go high in our brain,” Dr. Gupta explained.

Although the vicious cycle can be thwarted by turning off the device, Dr. Gupta characterized this as “impractical” when smartphones are so vital to daily communication. Rather, Dr. Gupta advocated a program of moderation, reserving the phone for useful tasks without succumbing to the siren song of apps that waste time.

The most conspicuous culprit is social media, which Dr. Gupta considers to be among the most Pavlovian triggers of cell phone addiction. However, she acknowledged that participation in social media has its justifications.

“I, myself, use social media for my own branding and marketing,” Dr. Gupta said.

The problem that users have is distinguishing between screen time that does and does not have value, according to Dr. Gupta. She indicated that many of those overusing their smart devices are being driven by the dopaminergic reward system, which is generally divorced from the real goals of life, such as personal satisfaction and activity that is rewarding monetarily or in other ways.

“I am not asking for these devices to be thrown out the window. I am advocating for moderation, balance, and real-life engagement,” Dr. Gupta said at the meeting, held in Atlanta and virtually.

She outlined a long list of practical suggestions, including turning off the alarms, chimes, and messages that engage the user into the vicious dopaminergic-reward system loop. She suggested mindfulness so that the user can distinguish between valuable device use and activity that is simply procrastination.

“The devices are designed to be addictive. They are designed to manipulate our brain,” she said. “Eliminate the reward. Let’s try to make our devices boring, unappealing, or enticing so that they only work as tools.”

The medical literature is filled with data that support the potential harms of excessive screen use, leading many others to make some of the same points. In 2017, Thomas N. Robinson, MD, professor of child health at Stanford (Calif.) University, reviewed data showing an association between screen media exposure and obesity in children and adolescents.

“This is an area crying out for more research,” Dr. Robinson said in an interview. The problem of screen time, sedentary behavior, and weight gain has been an issue since the television was invented, which was the point he made in his 2017 paper, but he agreed that the problem is only getting worse.

“Digital technology has become ubiquitous, touching nearly every aspect of people’s lives,” he said. Yet, as evidence grows that overuse of this technology can be harmful, it is creating a problem without a clear solution.

“There are few data about the efficacy of specific strategies to reduce harmful impacts of digital screen use,” he said.

While some of the solutions that Dr. Gupta described make sense, they are more easily described than executed. The dopaminergic reward system is strong and largely experienced subconsciously. Recruiting patients to recognize that dopaminergic rewards are not rewards in any true sense is already a challenge. Enlisting patients to take the difficult steps to avoid the behavioral cues might be even more difficult.

Dr. Gupta and Dr. Robinson report no potential conflicts of interest.

People with diabetes who had a poor-quality diet and food insecurity were significantly more likely to have poor glycemic and cholesterol control than were those with a healthier diet and food security, based on data from a national study of more than 2,000 individuals.

The American Diabetes Association recommends a high-quality diet for people with diabetes (PWD) to achieve treatment goals; however, roughly 18% of PWD in the United States are food insecure and/or have a poor-quality diet, Sarah S. Casagrande, PhD, of DLH Corporation, Silver Spring, Md., and colleagues wrote in a poster presented at the annual scientific sessions of the ADA in New Orleans.

To examine the impact of food insecurity and diet quality on diabetes and lipid management, the researchers reviewed data from 2,075 adults with self-reported diabetes who completed the National Health and Nutrition Examination Surveys between 2013 and 2018.

Diet quality was divided into quartiles based on the 2015 Healthy Eating Index. Food insecurity was assessed using a standard 10-item questionnaire including questions about running out of food and not being able to afford more, reducing meal sizes, eating less or not at all, and going hungry because of lack of money for food.

The logistic regression analysis controlled for factors including sociodemographics, health care use, smoking, diabetes medications, blood pressure medication use, cholesterol medication use, and body mass index.

Overall, 17.6% of the participants were food insecure and had a low-quality diet, 14.2% were food insecure with a high-quality diet, 33.1% were food secure with a low-quality diet, and 35.2% were food secure with a high-quality diet.

PWD in the food insecure/low-quality diet group were significantly more likely to be younger, non-Hispanic black or Hispanic, and uninsured compared to those in the food secure/high-quality diet group (P < .001 for all).

When the researchers examined glycemic control, they found that PWD in the food insecurity/low-quality diet groups were significantly more likely than were those with food security/high-quality diets to have hemoglobin A1c of at least 7.0% (adjusted odds ratio, 1.85), A1c of at least 8.0% (aOR, 1.79), low HDL cholesterol (aOR, 1.69), and high triglycerides (aOR, 3.26).

PWD with food insecurity but a high-quality diet also were significantly more likely than were those with food security and a high quality diet to have A1c of at least 7.0% (aOR, 1.69), A1c of at least 8.0% (aOR, 1.83), and high triglycerides (aOR, 2.44). PWD with food security but a low-quality diet were significantly more likely than was the food security/high-quality diet group to have A1c of at least 7% (aOR, 1.55).

The study findings were limited by several factors including the cross-sectional design, reliance on self-reports, and inability to distinguish between type 1 and type 2 diabetes, the researchers wrote.

However, the results were strengthened by the large, nationally representative sample and the inclusion of multiple clinical outcomes in the patient assessment, they said.

The results suggest that food insecurity had a significant impact on both glycemic control and cholesterol management independent of diet quality, the researchers noted. Based on these findings, health care providers treating PWD may wish to assess their patients’ food security status, and “interventions could address disparities in food security,” they concluded.
 

Food insecurity a growing problem

“With more communities being pushed into state of war, drought, and famine globally, it is important to track impact of food insecurity and low quality food on common medical conditions like diabetes in our vulnerable communities,” Romesh K. Khardori, MD, professor of medicine: endocrinology, and metabolism at Eastern Virginia Medical School, Norfolk, said in an interview.

Dr. Khardori, who was not involved in the study, said he was not surprised by the current study findings.

“Type of food, amount of food, and quality of food have been stressed in diabetes management for more than 100 years,” he said. “Organizations charged with recommendations, such as the ADA and American Dietetic Association, have regularly updated their recommendations,” he noted. “It was not surprising, therefore, to find food insecurity and low quality tied to poor glycemic control.”

The take-home message for clinicians is to consider the availability and quality of food that their patients are exposed to when evaluating barriers to proper glycemic control, Dr. Khardori emphasized.

However, additional research is needed to explore whether the prescription of a sufficient amount of good quality food would alleviate the adverse impact seen in the current study, he said.

The study was supported by the National Institute of Diabetes and Digestive and Kidney Diseases. The researchers and Dr. Khardori had no financial conflicts to disclose.

People with diabetes who had a poor-quality diet and food insecurity were significantly more likely to have poor glycemic and cholesterol control than were those with a healthier diet and food security, based on data from a national study of more than 2,000 individuals.

The American Diabetes Association recommends a high-quality diet for people with diabetes (PWD) to achieve treatment goals; however, roughly 18% of PWD in the United States are food insecure and/or have a poor-quality diet, Sarah S. Casagrande, PhD, of DLH Corporation, Silver Spring, Md., and colleagues wrote in a poster presented at the annual scientific sessions of the ADA in New Orleans.

To examine the impact of food insecurity and diet quality on diabetes and lipid management, the researchers reviewed data from 2,075 adults with self-reported diabetes who completed the National Health and Nutrition Examination Surveys between 2013 and 2018.

Diet quality was divided into quartiles based on the 2015 Healthy Eating Index. Food insecurity was assessed using a standard 10-item questionnaire including questions about running out of food and not being able to afford more, reducing meal sizes, eating less or not at all, and going hungry because of lack of money for food.

The logistic regression analysis controlled for factors including sociodemographics, health care use, smoking, diabetes medications, blood pressure medication use, cholesterol medication use, and body mass index.

Overall, 17.6% of the participants were food insecure and had a low-quality diet, 14.2% were food insecure with a high-quality diet, 33.1% were food secure with a low-quality diet, and 35.2% were food secure with a high-quality diet.

PWD in the food insecure/low-quality diet group were significantly more likely to be younger, non-Hispanic black or Hispanic, and uninsured compared to those in the food secure/high-quality diet group (P < .001 for all).

When the researchers examined glycemic control, they found that PWD in the food insecurity/low-quality diet groups were significantly more likely than were those with food security/high-quality diets to have hemoglobin A1c of at least 7.0% (adjusted odds ratio, 1.85), A1c of at least 8.0% (aOR, 1.79), low HDL cholesterol (aOR, 1.69), and high triglycerides (aOR, 3.26).

PWD with food insecurity but a high-quality diet also were significantly more likely than were those with food security and a high quality diet to have A1c of at least 7.0% (aOR, 1.69), A1c of at least 8.0% (aOR, 1.83), and high triglycerides (aOR, 2.44). PWD with food security but a low-quality diet were significantly more likely than was the food security/high-quality diet group to have A1c of at least 7% (aOR, 1.55).

The study findings were limited by several factors including the cross-sectional design, reliance on self-reports, and inability to distinguish between type 1 and type 2 diabetes, the researchers wrote.

However, the results were strengthened by the large, nationally representative sample and the inclusion of multiple clinical outcomes in the patient assessment, they said.

The results suggest that food insecurity had a significant impact on both glycemic control and cholesterol management independent of diet quality, the researchers noted. Based on these findings, health care providers treating PWD may wish to assess their patients’ food security status, and “interventions could address disparities in food security,” they concluded.
 

Food insecurity a growing problem

“With more communities being pushed into state of war, drought, and famine globally, it is important to track impact of food insecurity and low quality food on common medical conditions like diabetes in our vulnerable communities,” Romesh K. Khardori, MD, professor of medicine: endocrinology, and metabolism at Eastern Virginia Medical School, Norfolk, said in an interview.

Dr. Khardori, who was not involved in the study, said he was not surprised by the current study findings.

“Type of food, amount of food, and quality of food have been stressed in diabetes management for more than 100 years,” he said. “Organizations charged with recommendations, such as the ADA and American Dietetic Association, have regularly updated their recommendations,” he noted. “It was not surprising, therefore, to find food insecurity and low quality tied to poor glycemic control.”

The take-home message for clinicians is to consider the availability and quality of food that their patients are exposed to when evaluating barriers to proper glycemic control, Dr. Khardori emphasized.

However, additional research is needed to explore whether the prescription of a sufficient amount of good quality food would alleviate the adverse impact seen in the current study, he said.

The study was supported by the National Institute of Diabetes and Digestive and Kidney Diseases. The researchers and Dr. Khardori had no financial conflicts to disclose.

People with diabetes who had a poor-quality diet and food insecurity were significantly more likely to have poor glycemic and cholesterol control than were those with a healthier diet and food security, based on data from a national study of more than 2,000 individuals.

The American Diabetes Association recommends a high-quality diet for people with diabetes (PWD) to achieve treatment goals; however, roughly 18% of PWD in the United States are food insecure and/or have a poor-quality diet, Sarah S. Casagrande, PhD, of DLH Corporation, Silver Spring, Md., and colleagues wrote in a poster presented at the annual scientific sessions of the ADA in New Orleans.

To examine the impact of food insecurity and diet quality on diabetes and lipid management, the researchers reviewed data from 2,075 adults with self-reported diabetes who completed the National Health and Nutrition Examination Surveys between 2013 and 2018.

Diet quality was divided into quartiles based on the 2015 Healthy Eating Index. Food insecurity was assessed using a standard 10-item questionnaire including questions about running out of food and not being able to afford more, reducing meal sizes, eating less or not at all, and going hungry because of lack of money for food.

The logistic regression analysis controlled for factors including sociodemographics, health care use, smoking, diabetes medications, blood pressure medication use, cholesterol medication use, and body mass index.

Overall, 17.6% of the participants were food insecure and had a low-quality diet, 14.2% were food insecure with a high-quality diet, 33.1% were food secure with a low-quality diet, and 35.2% were food secure with a high-quality diet.

PWD in the food insecure/low-quality diet group were significantly more likely to be younger, non-Hispanic black or Hispanic, and uninsured compared to those in the food secure/high-quality diet group (P < .001 for all).

When the researchers examined glycemic control, they found that PWD in the food insecurity/low-quality diet groups were significantly more likely than were those with food security/high-quality diets to have hemoglobin A1c of at least 7.0% (adjusted odds ratio, 1.85), A1c of at least 8.0% (aOR, 1.79), low HDL cholesterol (aOR, 1.69), and high triglycerides (aOR, 3.26).

PWD with food insecurity but a high-quality diet also were significantly more likely than were those with food security and a high quality diet to have A1c of at least 7.0% (aOR, 1.69), A1c of at least 8.0% (aOR, 1.83), and high triglycerides (aOR, 2.44). PWD with food security but a low-quality diet were significantly more likely than was the food security/high-quality diet group to have A1c of at least 7% (aOR, 1.55).

The study findings were limited by several factors including the cross-sectional design, reliance on self-reports, and inability to distinguish between type 1 and type 2 diabetes, the researchers wrote.

However, the results were strengthened by the large, nationally representative sample and the inclusion of multiple clinical outcomes in the patient assessment, they said.

The results suggest that food insecurity had a significant impact on both glycemic control and cholesterol management independent of diet quality, the researchers noted. Based on these findings, health care providers treating PWD may wish to assess their patients’ food security status, and “interventions could address disparities in food security,” they concluded.
 

Food insecurity a growing problem

“With more communities being pushed into state of war, drought, and famine globally, it is important to track impact of food insecurity and low quality food on common medical conditions like diabetes in our vulnerable communities,” Romesh K. Khardori, MD, professor of medicine: endocrinology, and metabolism at Eastern Virginia Medical School, Norfolk, said in an interview.

Dr. Khardori, who was not involved in the study, said he was not surprised by the current study findings.

“Type of food, amount of food, and quality of food have been stressed in diabetes management for more than 100 years,” he said. “Organizations charged with recommendations, such as the ADA and American Dietetic Association, have regularly updated their recommendations,” he noted. “It was not surprising, therefore, to find food insecurity and low quality tied to poor glycemic control.”

The take-home message for clinicians is to consider the availability and quality of food that their patients are exposed to when evaluating barriers to proper glycemic control, Dr. Khardori emphasized.

However, additional research is needed to explore whether the prescription of a sufficient amount of good quality food would alleviate the adverse impact seen in the current study, he said.

The study was supported by the National Institute of Diabetes and Digestive and Kidney Diseases. The researchers and Dr. Khardori had no financial conflicts to disclose.

LONDON – A low-carbohydrate, high-fat (LCHF) diet reduced the progression of nonalcoholic fatty liver disease (NAFLD), and despite no calorie restriction, participants with both NAFLD and type 2 diabetes lost 5.8% of their body weight, according to a randomized controlled study.

“Based on these results, the LCHF diet may be recommended to people with NAFLD and type 2 diabetes,” said Camilla Dalby Hansen, MD, department of gastroenterology and hepatology, Odense University Hospital, Denmark, who presented the data at the International Liver Congress (ILC) 2022.  

“Basically, if you have fat in your liver, you will benefit from eating fat,” she said.

The LCHF diet was compared with a low-fat, high-carbohydrate diet more typically followed for these conditions. The low-fat diet was also found to reduce the progression of NAFLD, but to a lesser extent than the LCHF diet.

Dr. Dalby Hansen called their study one of the most extensive investigations of the LCHF diet in patients with type 2 diabetes and fatty liver disease.

“Combining this [reduction in NAFLD score] with the huge weight loss, the lower HbA1c [blood sugar], the lowering of blood pressure in women, the rise in HDL levels, and reduction in triglycerides – all in all, this diet is very promising,” she said.

Stephen Harrison, MD, visiting professor, University of Oxford, United Kingdom, medical director of Pinnacle Clinical Research and president of Summit Clinical Research, San Antonio, commended Dr. Dalby Hansen on her methodology, which included before-and-after liver biopsies. “It’s a heinous effort to do paired liver biopsies in a lifestyle modification trial. That’s huge.”

“This study tells me that the way we manage patients doesn’t change – it is still lifestyle modification,” said Dr. Harrison, who was not involved with the study. “It’s eat less [rather] than more. It’s exercise and try to lose weight. In the long term, we give patients benefit, and we show that the disease has improved, and we offer something that means they can maintain a healthy life.”

He added that the relatively small and short trial was informative.

“They improved the NAFLD activity score [NAS],” he said. “I don’t know by how much. There was no change in fibrosis, but we wouldn’t expect this at 6 months.”

“It’s provocative work, and it gives us healthy information about how we can help manage our patients from a lifestyle perspective,” he concluded.
 

‘Do not lose weight. Eat until you are full’

In the study, 110 participants with type 2 diabetes and NAFLD, aged 18-78 years, were allocated to the LCHF diet, and 55 were allocated to the low-fat diet for 6 months.

The researchers performed liver biopsies at baseline and 6 months, which were blinded for scoring.  

Participants had ongoing dietitian consultations, with follow-up visits at 3 and 6 months. Compliance was reported continuously through an online food diary platform.

The primary endpoint was change in glycemic control as measured by A1c level over 6 months. The secondary endpoints comprised the proportion of participants with changes in the NAS of at least 2 points over 6 months. Both these measures were compared between the two dietary groups.

The two groups were matched at baseline, with a mean age of 55-57 years, 58% were women, 89% with metabolic syndrome, and a mean BMI 34 kg/m².

In baseline liver disease, F1 level fibrosis was the most common (58%), followed by hepatic steatosis (S1, 47%; S2, 32%), with a median NAS of 3, and 19% had nonalcoholic steatohepatitis.

The special thing about these diets was that participants were told to “not lose weight, but eat until you are full,” remarked Dr. Dalby Hansen.

Those on the LCHF diet consumed an average of 61% energy from fat, 13% from carbohydrates, and 23% from protein, compared with the low-fat diet, which comprised an average of 29% energy from fat, 46% from carbohydrates, and 21% from protein.

“It’s a lot of fat and corresponds to a quarter of a liter of olive oil per day,” said Dr. Dalby Hansen. “They really had to change their mindset a lot, because it was difficult for them to start eating all these fats, especially since we’ve all been told for decades that it isn’t good. But we supported them, and they got into it.”

The LCHF diet was primarily comprised of unsaturated fats – for example, avocado, oil, nuts, and seeds – but also included saturated fats, such as cheese, cream, and high-fat dairy products. Participants were free to eat unsaturated and saturated fats, but Dr. Dalby Hansen and her team advised participants that “good” unsaturated fats were preferable.

“Also, this diet contained vegetables but no bread, no potatoes, no rice, and no pasta. It was low in carbohydrates, below 20%,” she added.
 

Improved glycemic control, reduced liver fat

“We found that the LCHF diet improved diabetes control, it reduced the fat in the liver, and, even though they’re eating as many calories as they were used to until they were full, they lost 5.8% of body weight,” said Dr. Dalby Hansen in reporting the results. Participants in the low-fat group lost only 1.8% of body weight.

However, mean calorie intake dropped in both groups, by –2.2% in the LCHF group and –8.7% in the low-fat group. 

“The LCHF diet improved the primary outcome of A1c by 9.5 mmol/mol, which is similar to some anti-diabetic medications, such as DPP-4 inhibitors and SGLT2 inhibitors,” she said.

The low-fat group reduced A1c by 3.4 mmol/mol, resulting in a between-group difference of 6.1 mmol/mol.

“Upon follow-up of 3 months, after stopping the diets, on average the participants in both groups returned their HbA1c levels to nearly baseline values,” she said. Results were adjusted for weight loss and baseline values.

Both diets also improved the NAS. The proportion of participants who improved their NAS score by 2 or more points was 22% in the LCHF group versus 17% in the low-fat group (P = 0.58). Additionally, in the LCHF group, 70% of participants improved their score by 1 or more points, compared with 49% in the low-fat group and fewer in the LCHF group experienced a worsening of their score (1% vs. 23%, respectively).

One participant on LCHF had high triglycerides of 12 mmol/L after 3 months. Overall, the low-density lipoprotein increased marginally by 0.2 mmol per liter in the high-fat group, said Dr. Dalby Hansen.

Dr. Dalby Hansen noted some limitations. The findings might not be applicable in more severe NAFLD, dietary assessment relied on self-reporting, no food was provided, and participants had to cook themselves. It was also an open-label study because of the nature of the intervention.
 

Some hope for more sustainable dieting

Many diets are difficult to adhere to, remarked Dr. Dalby Hansen. “We thought this [diet] might be easier to comply with in the longer term, and we hope that these results might provide patients with more options.”

She added that most people who started the diet adapted and complied with it. “However, it might not be for everyone, but I think we can say that if people try, and it fits into their lives, then they go for it.”

However, “it is not about going out and eating whatever fat and how much of it you want. It’s important that you cut the carbohydrates too,” she said. “With this approach, we really saw amazing results.”

Dr. Dalby Hansen added that having various diets available, including the LCHF one, meant that as clinicians they could empower patients to take control of their metabolic health.

“We can ask them directly, ‘What would fit into their life?’” she said. “We know that one size does not fit at all, and I believe that if we could engage patients more, then they can take control of their own situation.”

Asked whether these findings were enough to change guidelines, Zobair Younossi, MD, professor and chairman, department of medicine, Inova Fairfax Medical Campus, Falls Church, Va., remarked that it was the sugar at work here.

“Dietary fat – it’s not the same as fat in the liver, and this diet has more to do with the sugar levels,” he said.

“I’m always reluctant to take results from a short-term study without long-term follow-up,” Dr. Younossi said. “I want to know will patients live longer, and long-term data are needed for this. Until I have that strong evidence that outcomes are going to change, or at least some sign that the outcome is going to change, it is too early to change any guidelines.”

Dr. Dalby Hansen reports no relevant financial relationships. Dr. Harrison reported financial relationships with numerous pharmaceutical companies. Dr. Younossi reports the following financial relationships: research funds and/or consultant to Abbott, Allergan, Bristol Myers Squibb, Echosens, Genfit, Gilead Sciences, Intercept, Madrigal, Merck, and Novo Nordisk.

A version of this article first appeared on Medscape.com.

LONDON – A low-carbohydrate, high-fat (LCHF) diet reduced the progression of nonalcoholic fatty liver disease (NAFLD), and despite no calorie restriction, participants with both NAFLD and type 2 diabetes lost 5.8% of their body weight, according to a randomized controlled study.

“Based on these results, the LCHF diet may be recommended to people with NAFLD and type 2 diabetes,” said Camilla Dalby Hansen, MD, department of gastroenterology and hepatology, Odense University Hospital, Denmark, who presented the data at the International Liver Congress (ILC) 2022.  

“Basically, if you have fat in your liver, you will benefit from eating fat,” she said.

The LCHF diet was compared with a low-fat, high-carbohydrate diet more typically followed for these conditions. The low-fat diet was also found to reduce the progression of NAFLD, but to a lesser extent than the LCHF diet.

Dr. Dalby Hansen called their study one of the most extensive investigations of the LCHF diet in patients with type 2 diabetes and fatty liver disease.

“Combining this [reduction in NAFLD score] with the huge weight loss, the lower HbA1c [blood sugar], the lowering of blood pressure in women, the rise in HDL levels, and reduction in triglycerides – all in all, this diet is very promising,” she said.

Stephen Harrison, MD, visiting professor, University of Oxford, United Kingdom, medical director of Pinnacle Clinical Research and president of Summit Clinical Research, San Antonio, commended Dr. Dalby Hansen on her methodology, which included before-and-after liver biopsies. “It’s a heinous effort to do paired liver biopsies in a lifestyle modification trial. That’s huge.”

“This study tells me that the way we manage patients doesn’t change – it is still lifestyle modification,” said Dr. Harrison, who was not involved with the study. “It’s eat less [rather] than more. It’s exercise and try to lose weight. In the long term, we give patients benefit, and we show that the disease has improved, and we offer something that means they can maintain a healthy life.”

He added that the relatively small and short trial was informative.

“They improved the NAFLD activity score [NAS],” he said. “I don’t know by how much. There was no change in fibrosis, but we wouldn’t expect this at 6 months.”

“It’s provocative work, and it gives us healthy information about how we can help manage our patients from a lifestyle perspective,” he concluded.
 

‘Do not lose weight. Eat until you are full’

In the study, 110 participants with type 2 diabetes and NAFLD, aged 18-78 years, were allocated to the LCHF diet, and 55 were allocated to the low-fat diet for 6 months.

The researchers performed liver biopsies at baseline and 6 months, which were blinded for scoring.  

Participants had ongoing dietitian consultations, with follow-up visits at 3 and 6 months. Compliance was reported continuously through an online food diary platform.

The primary endpoint was change in glycemic control as measured by A1c level over 6 months. The secondary endpoints comprised the proportion of participants with changes in the NAS of at least 2 points over 6 months. Both these measures were compared between the two dietary groups.

The two groups were matched at baseline, with a mean age of 55-57 years, 58% were women, 89% with metabolic syndrome, and a mean BMI 34 kg/m².

In baseline liver disease, F1 level fibrosis was the most common (58%), followed by hepatic steatosis (S1, 47%; S2, 32%), with a median NAS of 3, and 19% had nonalcoholic steatohepatitis.

The special thing about these diets was that participants were told to “not lose weight, but eat until you are full,” remarked Dr. Dalby Hansen.

Those on the LCHF diet consumed an average of 61% energy from fat, 13% from carbohydrates, and 23% from protein, compared with the low-fat diet, which comprised an average of 29% energy from fat, 46% from carbohydrates, and 21% from protein.

“It’s a lot of fat and corresponds to a quarter of a liter of olive oil per day,” said Dr. Dalby Hansen. “They really had to change their mindset a lot, because it was difficult for them to start eating all these fats, especially since we’ve all been told for decades that it isn’t good. But we supported them, and they got into it.”

The LCHF diet was primarily comprised of unsaturated fats – for example, avocado, oil, nuts, and seeds – but also included saturated fats, such as cheese, cream, and high-fat dairy products. Participants were free to eat unsaturated and saturated fats, but Dr. Dalby Hansen and her team advised participants that “good” unsaturated fats were preferable.

“Also, this diet contained vegetables but no bread, no potatoes, no rice, and no pasta. It was low in carbohydrates, below 20%,” she added.
 

Improved glycemic control, reduced liver fat

“We found that the LCHF diet improved diabetes control, it reduced the fat in the liver, and, even though they’re eating as many calories as they were used to until they were full, they lost 5.8% of body weight,” said Dr. Dalby Hansen in reporting the results. Participants in the low-fat group lost only 1.8% of body weight.

However, mean calorie intake dropped in both groups, by –2.2% in the LCHF group and –8.7% in the low-fat group. 

“The LCHF diet improved the primary outcome of A1c by 9.5 mmol/mol, which is similar to some anti-diabetic medications, such as DPP-4 inhibitors and SGLT2 inhibitors,” she said.

The low-fat group reduced A1c by 3.4 mmol/mol, resulting in a between-group difference of 6.1 mmol/mol.

“Upon follow-up of 3 months, after stopping the diets, on average the participants in both groups returned their HbA1c levels to nearly baseline values,” she said. Results were adjusted for weight loss and baseline values.

Both diets also improved the NAS. The proportion of participants who improved their NAS score by 2 or more points was 22% in the LCHF group versus 17% in the low-fat group (P = 0.58). Additionally, in the LCHF group, 70% of participants improved their score by 1 or more points, compared with 49% in the low-fat group and fewer in the LCHF group experienced a worsening of their score (1% vs. 23%, respectively).

One participant on LCHF had high triglycerides of 12 mmol/L after 3 months. Overall, the low-density lipoprotein increased marginally by 0.2 mmol per liter in the high-fat group, said Dr. Dalby Hansen.

Dr. Dalby Hansen noted some limitations. The findings might not be applicable in more severe NAFLD, dietary assessment relied on self-reporting, no food was provided, and participants had to cook themselves. It was also an open-label study because of the nature of the intervention.
 

Some hope for more sustainable dieting

Many diets are difficult to adhere to, remarked Dr. Dalby Hansen. “We thought this [diet] might be easier to comply with in the longer term, and we hope that these results might provide patients with more options.”

She added that most people who started the diet adapted and complied with it. “However, it might not be for everyone, but I think we can say that if people try, and it fits into their lives, then they go for it.”

However, “it is not about going out and eating whatever fat and how much of it you want. It’s important that you cut the carbohydrates too,” she said. “With this approach, we really saw amazing results.”

Dr. Dalby Hansen added that having various diets available, including the LCHF one, meant that as clinicians they could empower patients to take control of their metabolic health.

“We can ask them directly, ‘What would fit into their life?’” she said. “We know that one size does not fit at all, and I believe that if we could engage patients more, then they can take control of their own situation.”

Asked whether these findings were enough to change guidelines, Zobair Younossi, MD, professor and chairman, department of medicine, Inova Fairfax Medical Campus, Falls Church, Va., remarked that it was the sugar at work here.

“Dietary fat – it’s not the same as fat in the liver, and this diet has more to do with the sugar levels,” he said.

“I’m always reluctant to take results from a short-term study without long-term follow-up,” Dr. Younossi said. “I want to know will patients live longer, and long-term data are needed for this. Until I have that strong evidence that outcomes are going to change, or at least some sign that the outcome is going to change, it is too early to change any guidelines.”

Dr. Dalby Hansen reports no relevant financial relationships. Dr. Harrison reported financial relationships with numerous pharmaceutical companies. Dr. Younossi reports the following financial relationships: research funds and/or consultant to Abbott, Allergan, Bristol Myers Squibb, Echosens, Genfit, Gilead Sciences, Intercept, Madrigal, Merck, and Novo Nordisk.

A version of this article first appeared on Medscape.com.

LONDON – A low-carbohydrate, high-fat (LCHF) diet reduced the progression of nonalcoholic fatty liver disease (NAFLD), and despite no calorie restriction, participants with both NAFLD and type 2 diabetes lost 5.8% of their body weight, according to a randomized controlled study.

“Based on these results, the LCHF diet may be recommended to people with NAFLD and type 2 diabetes,” said Camilla Dalby Hansen, MD, department of gastroenterology and hepatology, Odense University Hospital, Denmark, who presented the data at the International Liver Congress (ILC) 2022.  

“Basically, if you have fat in your liver, you will benefit from eating fat,” she said.

The LCHF diet was compared with a low-fat, high-carbohydrate diet more typically followed for these conditions. The low-fat diet was also found to reduce the progression of NAFLD, but to a lesser extent than the LCHF diet.

Dr. Dalby Hansen called their study one of the most extensive investigations of the LCHF diet in patients with type 2 diabetes and fatty liver disease.

“Combining this [reduction in NAFLD score] with the huge weight loss, the lower HbA1c [blood sugar], the lowering of blood pressure in women, the rise in HDL levels, and reduction in triglycerides – all in all, this diet is very promising,” she said.

Stephen Harrison, MD, visiting professor, University of Oxford, United Kingdom, medical director of Pinnacle Clinical Research and president of Summit Clinical Research, San Antonio, commended Dr. Dalby Hansen on her methodology, which included before-and-after liver biopsies. “It’s a heinous effort to do paired liver biopsies in a lifestyle modification trial. That’s huge.”

“This study tells me that the way we manage patients doesn’t change – it is still lifestyle modification,” said Dr. Harrison, who was not involved with the study. “It’s eat less [rather] than more. It’s exercise and try to lose weight. In the long term, we give patients benefit, and we show that the disease has improved, and we offer something that means they can maintain a healthy life.”

He added that the relatively small and short trial was informative.

“They improved the NAFLD activity score [NAS],” he said. “I don’t know by how much. There was no change in fibrosis, but we wouldn’t expect this at 6 months.”

“It’s provocative work, and it gives us healthy information about how we can help manage our patients from a lifestyle perspective,” he concluded.
 

‘Do not lose weight. Eat until you are full’

In the study, 110 participants with type 2 diabetes and NAFLD, aged 18-78 years, were allocated to the LCHF diet, and 55 were allocated to the low-fat diet for 6 months.

The researchers performed liver biopsies at baseline and 6 months, which were blinded for scoring.  

Participants had ongoing dietitian consultations, with follow-up visits at 3 and 6 months. Compliance was reported continuously through an online food diary platform.

The primary endpoint was change in glycemic control as measured by A1c level over 6 months. The secondary endpoints comprised the proportion of participants with changes in the NAS of at least 2 points over 6 months. Both these measures were compared between the two dietary groups.

The two groups were matched at baseline, with a mean age of 55-57 years, 58% were women, 89% with metabolic syndrome, and a mean BMI 34 kg/m².

In baseline liver disease, F1 level fibrosis was the most common (58%), followed by hepatic steatosis (S1, 47%; S2, 32%), with a median NAS of 3, and 19% had nonalcoholic steatohepatitis.

The special thing about these diets was that participants were told to “not lose weight, but eat until you are full,” remarked Dr. Dalby Hansen.

Those on the LCHF diet consumed an average of 61% energy from fat, 13% from carbohydrates, and 23% from protein, compared with the low-fat diet, which comprised an average of 29% energy from fat, 46% from carbohydrates, and 21% from protein.

“It’s a lot of fat and corresponds to a quarter of a liter of olive oil per day,” said Dr. Dalby Hansen. “They really had to change their mindset a lot, because it was difficult for them to start eating all these fats, especially since we’ve all been told for decades that it isn’t good. But we supported them, and they got into it.”

The LCHF diet was primarily comprised of unsaturated fats – for example, avocado, oil, nuts, and seeds – but also included saturated fats, such as cheese, cream, and high-fat dairy products. Participants were free to eat unsaturated and saturated fats, but Dr. Dalby Hansen and her team advised participants that “good” unsaturated fats were preferable.

“Also, this diet contained vegetables but no bread, no potatoes, no rice, and no pasta. It was low in carbohydrates, below 20%,” she added.
 

Improved glycemic control, reduced liver fat

“We found that the LCHF diet improved diabetes control, it reduced the fat in the liver, and, even though they’re eating as many calories as they were used to until they were full, they lost 5.8% of body weight,” said Dr. Dalby Hansen in reporting the results. Participants in the low-fat group lost only 1.8% of body weight.

However, mean calorie intake dropped in both groups, by –2.2% in the LCHF group and –8.7% in the low-fat group. 

“The LCHF diet improved the primary outcome of A1c by 9.5 mmol/mol, which is similar to some anti-diabetic medications, such as DPP-4 inhibitors and SGLT2 inhibitors,” she said.

The low-fat group reduced A1c by 3.4 mmol/mol, resulting in a between-group difference of 6.1 mmol/mol.

“Upon follow-up of 3 months, after stopping the diets, on average the participants in both groups returned their HbA1c levels to nearly baseline values,” she said. Results were adjusted for weight loss and baseline values.

Both diets also improved the NAS. The proportion of participants who improved their NAS score by 2 or more points was 22% in the LCHF group versus 17% in the low-fat group (P = 0.58). Additionally, in the LCHF group, 70% of participants improved their score by 1 or more points, compared with 49% in the low-fat group and fewer in the LCHF group experienced a worsening of their score (1% vs. 23%, respectively).

One participant on LCHF had high triglycerides of 12 mmol/L after 3 months. Overall, the low-density lipoprotein increased marginally by 0.2 mmol per liter in the high-fat group, said Dr. Dalby Hansen.

Dr. Dalby Hansen noted some limitations. The findings might not be applicable in more severe NAFLD, dietary assessment relied on self-reporting, no food was provided, and participants had to cook themselves. It was also an open-label study because of the nature of the intervention.
 

Some hope for more sustainable dieting

Many diets are difficult to adhere to, remarked Dr. Dalby Hansen. “We thought this [diet] might be easier to comply with in the longer term, and we hope that these results might provide patients with more options.”

She added that most people who started the diet adapted and complied with it. “However, it might not be for everyone, but I think we can say that if people try, and it fits into their lives, then they go for it.”

However, “it is not about going out and eating whatever fat and how much of it you want. It’s important that you cut the carbohydrates too,” she said. “With this approach, we really saw amazing results.”

Dr. Dalby Hansen added that having various diets available, including the LCHF one, meant that as clinicians they could empower patients to take control of their metabolic health.

“We can ask them directly, ‘What would fit into their life?’” she said. “We know that one size does not fit at all, and I believe that if we could engage patients more, then they can take control of their own situation.”

Asked whether these findings were enough to change guidelines, Zobair Younossi, MD, professor and chairman, department of medicine, Inova Fairfax Medical Campus, Falls Church, Va., remarked that it was the sugar at work here.

“Dietary fat – it’s not the same as fat in the liver, and this diet has more to do with the sugar levels,” he said.

“I’m always reluctant to take results from a short-term study without long-term follow-up,” Dr. Younossi said. “I want to know will patients live longer, and long-term data are needed for this. Until I have that strong evidence that outcomes are going to change, or at least some sign that the outcome is going to change, it is too early to change any guidelines.”

Dr. Dalby Hansen reports no relevant financial relationships. Dr. Harrison reported financial relationships with numerous pharmaceutical companies. Dr. Younossi reports the following financial relationships: research funds and/or consultant to Abbott, Allergan, Bristol Myers Squibb, Echosens, Genfit, Gilead Sciences, Intercept, Madrigal, Merck, and Novo Nordisk.

A version of this article first appeared on Medscape.com.

LONDON – Weight loss, lipid reductions, and “robust improvements” in lipid species associated with nonalcoholic fatty liver disease were achieved in patients who were treated with pemvidutide in a first-in-human, phase 1 clinical trial reported at the annual International Liver Congress, sponsored by the European Association for the Study of the Liver.

The presenting study investigator, Stephen A. Harrison, MD, said that pemvidutide, which is also being developed for the treatment of obesity, appeared to be well tolerated. There were no serious or severe adverse events, and no patient had to discontinue treatment because of side effects.

Sara Freeman/MDedge News

Overall, “pemvidutide represents a promising new agent,” said Dr. Harrison, medical director of Pinnacle Research in San Antonio, Texas.
 

Dual incretin effect

Pemvidutide is a “balanced” dual agonist of glucagon-like peptide 1 (GLP-1) and glucagon, Dr. Harrison explained in his oral abstract.

“With glucagon, we are working to drive energy expenditure up, and with GLP-1, we’re decreasing food intake,” Dr. Harrison said.

What might set pemvidutide apart from other incretins lies within its structure, Dr. Harrison suggested. The structure has two main regions – one with greater GLP-1 specificity and the other with greater glucagon specificity, and these two areas are linked by a propriety technology called a EuPort^™ domain. This is an area which allows the drug to bind to albumin, which increases its serum half-life and enables weekly dosing while slowing its entry into the bloodstream.

“Ultimately, we think that this has impacts, hypothetically, on tolerability and potentially mitigating the need for dose escalation,” said Dr. Harrison.
 

Weight loss results

The phase 1 study Dr. Harrison presented had a randomized, double-blind, placebo-controlled design with single and multiple ascending doses (SAD/MAD) of pemvidutide being tested. He presented data on the MAD phase only, noting that the SAD phase had been used to determine what doses to use in the latter.

Seventy individuals with a body mass index of between 25 and 40 kg/m² were recruited and 34 of these were enrolled in the MAD phase of the study. Three doses of pemvidutide were used, given subcutaneously once a week for 12 weeks: Seven participants received 1.2 mg, 9 were given 1.8 mg, 11 had 2.4 mg, and 7 subjects were treated with placebo. Dr. Harrison noted that there were no caloric restrictions in the trial and no lifestyle modifications or interventions.

The average age of study participants ranged from 27 to 35 years and the mean BMI was 30-31 kg/m² across each group, with their lipid parameters in the upper range of normal.

Clear weight loss reductions were seen across all the pemvidutide groups versus placebo, with the greatest percentage changes in weight loss seen with the two higher doses used. At week 12, there was a 4.9%, 10.3% and 9.0% weight loss in the 1.2-mg, 1.8-mg and 2.4-mg pemvidutide groups compared to 1.6% in placebo-treated individuals.

All patients in the 1.8-mg group achieved a 5% or greater weight loss, Dr. Harrison observed, but there “was a plateauing” effect with the 2.4-mg dose with 89% of patients achieving this target. In comparison, a third of patients on the lowest dose and 20% of those on placebo achieved this target.

The trajectory of weight loss seen in the trial suggests that “the rate of weight loss would continue beyond 12 weeks if we were to continue the therapy” Dr. Harrison said.
 

Lipid changes and liver fat reductions

Levels of serum lipids from baseline to week 12 fell to a greater extent with pemvidutide treatment than with placebo, in the range of –27% for total cholesterol in the two highest dose groups, –25% for LDL-cholesterol for those groups, –37% for triglycerides for the 1.2- and 1.8-mg groups, and reductions in apolipoprotein B were seen.

“We saw an initial decline in HDL [high-density lipoprotein],” Dr. Harrison said, noting that “this is consistent with prior studies looking at rapid weight loss, and over time, this mitigates as you continue to treat at least based on other mechanisms of action or other drugs with similar mechanisms.”

Pemvidutide treatment was also associated with increased lipid oxidation and decreased lipid synthesis, and “there was a robust decrease in lipids implicated in NASH inflammation,” Dr. Harrison pointed out.

Importantly, in five of eight participants who had high levels of liver fat at baseline – defined as a 5% or greater magnetic resonance imaging–derived proton-density-fat-fraction (MRI-PDFF) – showed a decrease to undetectable limits (1.5% or less). This was a greater than 90% reduction in liver fat, Dr. Harrison said. All five patients were in the 1.8-mg and 2.4-mg groups.

As for side effects, these were “predominantly upper GI, with nausea and vomiting.” These were mild in most cases, but he pointed out that five patients treated with the 1.8-mg dose experienced moderate nausea and three experienced moderate vomiting. Mild diarrhea and constipation were also seen in two of patients given this dose but was not reported in any of the other groups.

During the discussion following the presentation, it was pointed out that there was no clear dose-dependent effect considering the 1.8-mg dose seemed to have a stronger effect in some areas than the 2.4-mg dose. That’s a fair point, Dr. Harrison responded, reiterating it was a small study with a short treatment duration, but that there did look like a plateauing effect, “at least in patients with a mean BMI of between 30 and 31.”

Dr. Harrison was asked about potential effects on insulin levels and if that was a worry because, if glucagon is stimulated, it could increase insulin. That in turn might encourage insulin resistance and promote worse outcomes.

“If you look outside of just this program, glucagon agonism has been dosed in a lot of patients over time, and we haven’t seen that,” Dr. Harrison replied. Pemvidutide is an agonist rather than antagonist, so perhaps the [nonalcoholic steatohepatitis]–inducing effects seen before with glucagon antagonism won’t occur, he suggested.

Dr. Harrison disclosed ties to Altimmune (the study sponsor), Akero, Axcella, Bristol Myers Squibb, Cirius, CiVi Biopharma, Conatus, Corcept, CymaBay, Enyo, Galectin, Genentech, Genfit, Gilead, Hepion, Hightide, HistoIndex, Intercept, Madrigal, Metacrine, NGM Bio, Novartis, Novo Nordisk, NorthSea, Pfizer, Sagimet, Viking, and 89Bio.

LONDON – Weight loss, lipid reductions, and “robust improvements” in lipid species associated with nonalcoholic fatty liver disease were achieved in patients who were treated with pemvidutide in a first-in-human, phase 1 clinical trial reported at the annual International Liver Congress, sponsored by the European Association for the Study of the Liver.

The presenting study investigator, Stephen A. Harrison, MD, said that pemvidutide, which is also being developed for the treatment of obesity, appeared to be well tolerated. There were no serious or severe adverse events, and no patient had to discontinue treatment because of side effects.

Sara Freeman/MDedge News

Overall, “pemvidutide represents a promising new agent,” said Dr. Harrison, medical director of Pinnacle Research in San Antonio, Texas.
 

Dual incretin effect

Pemvidutide is a “balanced” dual agonist of glucagon-like peptide 1 (GLP-1) and glucagon, Dr. Harrison explained in his oral abstract.

“With glucagon, we are working to drive energy expenditure up, and with GLP-1, we’re decreasing food intake,” Dr. Harrison said.

What might set pemvidutide apart from other incretins lies within its structure, Dr. Harrison suggested. The structure has two main regions – one with greater GLP-1 specificity and the other with greater glucagon specificity, and these two areas are linked by a propriety technology called a EuPort^™ domain. This is an area which allows the drug to bind to albumin, which increases its serum half-life and enables weekly dosing while slowing its entry into the bloodstream.

“Ultimately, we think that this has impacts, hypothetically, on tolerability and potentially mitigating the need for dose escalation,” said Dr. Harrison.
 

Weight loss results

The phase 1 study Dr. Harrison presented had a randomized, double-blind, placebo-controlled design with single and multiple ascending doses (SAD/MAD) of pemvidutide being tested. He presented data on the MAD phase only, noting that the SAD phase had been used to determine what doses to use in the latter.

Seventy individuals with a body mass index of between 25 and 40 kg/m² were recruited and 34 of these were enrolled in the MAD phase of the study. Three doses of pemvidutide were used, given subcutaneously once a week for 12 weeks: Seven participants received 1.2 mg, 9 were given 1.8 mg, 11 had 2.4 mg, and 7 subjects were treated with placebo. Dr. Harrison noted that there were no caloric restrictions in the trial and no lifestyle modifications or interventions.

The average age of study participants ranged from 27 to 35 years and the mean BMI was 30-31 kg/m² across each group, with their lipid parameters in the upper range of normal.

Clear weight loss reductions were seen across all the pemvidutide groups versus placebo, with the greatest percentage changes in weight loss seen with the two higher doses used. At week 12, there was a 4.9%, 10.3% and 9.0% weight loss in the 1.2-mg, 1.8-mg and 2.4-mg pemvidutide groups compared to 1.6% in placebo-treated individuals.

All patients in the 1.8-mg group achieved a 5% or greater weight loss, Dr. Harrison observed, but there “was a plateauing” effect with the 2.4-mg dose with 89% of patients achieving this target. In comparison, a third of patients on the lowest dose and 20% of those on placebo achieved this target.

The trajectory of weight loss seen in the trial suggests that “the rate of weight loss would continue beyond 12 weeks if we were to continue the therapy” Dr. Harrison said.
 

Lipid changes and liver fat reductions

Levels of serum lipids from baseline to week 12 fell to a greater extent with pemvidutide treatment than with placebo, in the range of –27% for total cholesterol in the two highest dose groups, –25% for LDL-cholesterol for those groups, –37% for triglycerides for the 1.2- and 1.8-mg groups, and reductions in apolipoprotein B were seen.

“We saw an initial decline in HDL [high-density lipoprotein],” Dr. Harrison said, noting that “this is consistent with prior studies looking at rapid weight loss, and over time, this mitigates as you continue to treat at least based on other mechanisms of action or other drugs with similar mechanisms.”

Pemvidutide treatment was also associated with increased lipid oxidation and decreased lipid synthesis, and “there was a robust decrease in lipids implicated in NASH inflammation,” Dr. Harrison pointed out.

Importantly, in five of eight participants who had high levels of liver fat at baseline – defined as a 5% or greater magnetic resonance imaging–derived proton-density-fat-fraction (MRI-PDFF) – showed a decrease to undetectable limits (1.5% or less). This was a greater than 90% reduction in liver fat, Dr. Harrison said. All five patients were in the 1.8-mg and 2.4-mg groups.

As for side effects, these were “predominantly upper GI, with nausea and vomiting.” These were mild in most cases, but he pointed out that five patients treated with the 1.8-mg dose experienced moderate nausea and three experienced moderate vomiting. Mild diarrhea and constipation were also seen in two of patients given this dose but was not reported in any of the other groups.

During the discussion following the presentation, it was pointed out that there was no clear dose-dependent effect considering the 1.8-mg dose seemed to have a stronger effect in some areas than the 2.4-mg dose. That’s a fair point, Dr. Harrison responded, reiterating it was a small study with a short treatment duration, but that there did look like a plateauing effect, “at least in patients with a mean BMI of between 30 and 31.”

Dr. Harrison was asked about potential effects on insulin levels and if that was a worry because, if glucagon is stimulated, it could increase insulin. That in turn might encourage insulin resistance and promote worse outcomes.

“If you look outside of just this program, glucagon agonism has been dosed in a lot of patients over time, and we haven’t seen that,” Dr. Harrison replied. Pemvidutide is an agonist rather than antagonist, so perhaps the [nonalcoholic steatohepatitis]–inducing effects seen before with glucagon antagonism won’t occur, he suggested.

Dr. Harrison disclosed ties to Altimmune (the study sponsor), Akero, Axcella, Bristol Myers Squibb, Cirius, CiVi Biopharma, Conatus, Corcept, CymaBay, Enyo, Galectin, Genentech, Genfit, Gilead, Hepion, Hightide, HistoIndex, Intercept, Madrigal, Metacrine, NGM Bio, Novartis, Novo Nordisk, NorthSea, Pfizer, Sagimet, Viking, and 89Bio.

LONDON – Weight loss, lipid reductions, and “robust improvements” in lipid species associated with nonalcoholic fatty liver disease were achieved in patients who were treated with pemvidutide in a first-in-human, phase 1 clinical trial reported at the annual International Liver Congress, sponsored by the European Association for the Study of the Liver.

The presenting study investigator, Stephen A. Harrison, MD, said that pemvidutide, which is also being developed for the treatment of obesity, appeared to be well tolerated. There were no serious or severe adverse events, and no patient had to discontinue treatment because of side effects.

Sara Freeman/MDedge News

Overall, “pemvidutide represents a promising new agent,” said Dr. Harrison, medical director of Pinnacle Research in San Antonio, Texas.
 

Dual incretin effect

Pemvidutide is a “balanced” dual agonist of glucagon-like peptide 1 (GLP-1) and glucagon, Dr. Harrison explained in his oral abstract.

“With glucagon, we are working to drive energy expenditure up, and with GLP-1, we’re decreasing food intake,” Dr. Harrison said.

What might set pemvidutide apart from other incretins lies within its structure, Dr. Harrison suggested. The structure has two main regions – one with greater GLP-1 specificity and the other with greater glucagon specificity, and these two areas are linked by a propriety technology called a EuPort^™ domain. This is an area which allows the drug to bind to albumin, which increases its serum half-life and enables weekly dosing while slowing its entry into the bloodstream.

“Ultimately, we think that this has impacts, hypothetically, on tolerability and potentially mitigating the need for dose escalation,” said Dr. Harrison.
 

Weight loss results

The phase 1 study Dr. Harrison presented had a randomized, double-blind, placebo-controlled design with single and multiple ascending doses (SAD/MAD) of pemvidutide being tested. He presented data on the MAD phase only, noting that the SAD phase had been used to determine what doses to use in the latter.

Seventy individuals with a body mass index of between 25 and 40 kg/m² were recruited and 34 of these were enrolled in the MAD phase of the study. Three doses of pemvidutide were used, given subcutaneously once a week for 12 weeks: Seven participants received 1.2 mg, 9 were given 1.8 mg, 11 had 2.4 mg, and 7 subjects were treated with placebo. Dr. Harrison noted that there were no caloric restrictions in the trial and no lifestyle modifications or interventions.

The average age of study participants ranged from 27 to 35 years and the mean BMI was 30-31 kg/m² across each group, with their lipid parameters in the upper range of normal.

Clear weight loss reductions were seen across all the pemvidutide groups versus placebo, with the greatest percentage changes in weight loss seen with the two higher doses used. At week 12, there was a 4.9%, 10.3% and 9.0% weight loss in the 1.2-mg, 1.8-mg and 2.4-mg pemvidutide groups compared to 1.6% in placebo-treated individuals.

All patients in the 1.8-mg group achieved a 5% or greater weight loss, Dr. Harrison observed, but there “was a plateauing” effect with the 2.4-mg dose with 89% of patients achieving this target. In comparison, a third of patients on the lowest dose and 20% of those on placebo achieved this target.

The trajectory of weight loss seen in the trial suggests that “the rate of weight loss would continue beyond 12 weeks if we were to continue the therapy” Dr. Harrison said.
 

Lipid changes and liver fat reductions

Levels of serum lipids from baseline to week 12 fell to a greater extent with pemvidutide treatment than with placebo, in the range of –27% for total cholesterol in the two highest dose groups, –25% for LDL-cholesterol for those groups, –37% for triglycerides for the 1.2- and 1.8-mg groups, and reductions in apolipoprotein B were seen.

“We saw an initial decline in HDL [high-density lipoprotein],” Dr. Harrison said, noting that “this is consistent with prior studies looking at rapid weight loss, and over time, this mitigates as you continue to treat at least based on other mechanisms of action or other drugs with similar mechanisms.”

Pemvidutide treatment was also associated with increased lipid oxidation and decreased lipid synthesis, and “there was a robust decrease in lipids implicated in NASH inflammation,” Dr. Harrison pointed out.

Importantly, in five of eight participants who had high levels of liver fat at baseline – defined as a 5% or greater magnetic resonance imaging–derived proton-density-fat-fraction (MRI-PDFF) – showed a decrease to undetectable limits (1.5% or less). This was a greater than 90% reduction in liver fat, Dr. Harrison said. All five patients were in the 1.8-mg and 2.4-mg groups.

As for side effects, these were “predominantly upper GI, with nausea and vomiting.” These were mild in most cases, but he pointed out that five patients treated with the 1.8-mg dose experienced moderate nausea and three experienced moderate vomiting. Mild diarrhea and constipation were also seen in two of patients given this dose but was not reported in any of the other groups.

During the discussion following the presentation, it was pointed out that there was no clear dose-dependent effect considering the 1.8-mg dose seemed to have a stronger effect in some areas than the 2.4-mg dose. That’s a fair point, Dr. Harrison responded, reiterating it was a small study with a short treatment duration, but that there did look like a plateauing effect, “at least in patients with a mean BMI of between 30 and 31.”

Dr. Harrison was asked about potential effects on insulin levels and if that was a worry because, if glucagon is stimulated, it could increase insulin. That in turn might encourage insulin resistance and promote worse outcomes.

“If you look outside of just this program, glucagon agonism has been dosed in a lot of patients over time, and we haven’t seen that,” Dr. Harrison replied. Pemvidutide is an agonist rather than antagonist, so perhaps the [nonalcoholic steatohepatitis]–inducing effects seen before with glucagon antagonism won’t occur, he suggested.

Dr. Harrison disclosed ties to Altimmune (the study sponsor), Akero, Axcella, Bristol Myers Squibb, Cirius, CiVi Biopharma, Conatus, Corcept, CymaBay, Enyo, Galectin, Genentech, Genfit, Gilead, Hepion, Hightide, HistoIndex, Intercept, Madrigal, Metacrine, NGM Bio, Novartis, Novo Nordisk, NorthSea, Pfizer, Sagimet, Viking, and 89Bio.

Pregnancy termination for medical reasons had been part of the fabric of everyday health care in the United States since the Supreme Court’s 1973 Roe v. Wade decision, which the current high court overturned in a ruling announced on June 24.

That means many clinicians across specialties are entering uncharted territory with the country’s new patchwork of abortion legality. Some specialties, cardiology among them, may feel the impact more than others.

javi_indy/ Thinkstock

“Unfortunately,” Dr. Haythe said, “many of the states that are going to make or have made abortion illegal are not providing that kind of preconception counseling or good prenatal care to women.”

Cardiologists can provide such counseling to their female patients of childbearing age who have high-risk cardiac conditions, “but not everybody knows that they have a heart problem when they get pregnant, and not everybody is getting screened for heart problems when they’re of childbearing age,” Dr. Haythe said.

“Sometimes it’s not clear whether the problems could have been picked up until a woman is pregnant and has started to have symptoms.” For example, “a lot of women with poor access to health care have rheumatic heart disease. They may have no idea that they have severe aortic stenosis, and it’s not until their second trimester that they start to feel really short of breath.” Often that can be treated in the cath lab, “but again, that’s putting the woman and the baby at risk.”

Cardiologists in states where abortion is illegal will still present the option to their patients with high-risk pregnancies, noted Dr. Haythe. But the conversation may sound something like, “you are at very high risk, termination of the pregnancy takes that risk away, but you’ll have to find a state where it’s legal to do that.”

Dr. Park said such a situation, when abortion is recommended but locally unavailable, is much like any other in cardiology for which the patient may want a second opinion. If a center “doesn’t have the capability or the technology to offer a certain treatment, the patient can opt to seek another opinion at another center,” she said. “Patients will often travel out of state to get the care they need.”

A requirement for out-of-state travel to obtain abortions is likely to worsen socioeconomic disparities in health care, Dr. Bond observed, “because we know that those who are low-income won’t be able to afford that travel.”

Dr. Bond is cosignatory on a statement from the Association of Black Cardiologists (ABC) responding to the high court’s ruling in Dobbs v. Jackson. “This decision will isolate the poor, socioeconomically disadvantaged, and minority populations specifically, widening the already large gaps in health care for our most vulnerable communities,” it states.

“The loss of broad protections supporting the medical and often lifesaving procedure of abortions is likely to have a real impact on the maternal mortality rate, especially in those with congenital and/or acquired cardiovascular conditions where evidence-based guidelines advise at times on termination of such high-risk pregnancies.”

The ABC, it states, “believes that every woman, and every person, should be afforded the right to safe, accessible, legal, timely, patient-centered, equitable, and affordable health care.”

The American College of Cardiology (ACC) released a statement on the matter June 24, signed by its president, Edward T.A. Fry, MD, along with five former ACC presidents. “While the ACC has no official policy on abortion, clinical practice guidelines and other clinical guidance tools address the dangers of pregnancy in certain patient populations at higher risk of death or serious cardiac events.”

The college, it states, is “deeply concerned about the potential implications of the Supreme Court decision regarding Roe vs. Wade on the ability of patients and clinicians to engage in important shared discussions about maternal health, or to remove previously available health care options.”

Dr. Bond proposed that a “vocal stance” from medical societies involved in women’s health, “perhaps even a collective stance from our cardiovascular societies and our obstetrics societies,” would also perhaps reach “the masses of doctors in private practice who are dealing with these patients.”

A version of this article first appeared on Medscape.com.

Pregnancy termination for medical reasons had been part of the fabric of everyday health care in the United States since the Supreme Court’s 1973 Roe v. Wade decision, which the current high court overturned in a ruling announced on June 24.

That means many clinicians across specialties are entering uncharted territory with the country’s new patchwork of abortion legality. Some specialties, cardiology among them, may feel the impact more than others.

javi_indy/ Thinkstock

“Unfortunately,” Dr. Haythe said, “many of the states that are going to make or have made abortion illegal are not providing that kind of preconception counseling or good prenatal care to women.”

Cardiologists can provide such counseling to their female patients of childbearing age who have high-risk cardiac conditions, “but not everybody knows that they have a heart problem when they get pregnant, and not everybody is getting screened for heart problems when they’re of childbearing age,” Dr. Haythe said.

“Sometimes it’s not clear whether the problems could have been picked up until a woman is pregnant and has started to have symptoms.” For example, “a lot of women with poor access to health care have rheumatic heart disease. They may have no idea that they have severe aortic stenosis, and it’s not until their second trimester that they start to feel really short of breath.” Often that can be treated in the cath lab, “but again, that’s putting the woman and the baby at risk.”

Cardiologists in states where abortion is illegal will still present the option to their patients with high-risk pregnancies, noted Dr. Haythe. But the conversation may sound something like, “you are at very high risk, termination of the pregnancy takes that risk away, but you’ll have to find a state where it’s legal to do that.”

Dr. Park said such a situation, when abortion is recommended but locally unavailable, is much like any other in cardiology for which the patient may want a second opinion. If a center “doesn’t have the capability or the technology to offer a certain treatment, the patient can opt to seek another opinion at another center,” she said. “Patients will often travel out of state to get the care they need.”

A requirement for out-of-state travel to obtain abortions is likely to worsen socioeconomic disparities in health care, Dr. Bond observed, “because we know that those who are low-income won’t be able to afford that travel.”

Dr. Bond is cosignatory on a statement from the Association of Black Cardiologists (ABC) responding to the high court’s ruling in Dobbs v. Jackson. “This decision will isolate the poor, socioeconomically disadvantaged, and minority populations specifically, widening the already large gaps in health care for our most vulnerable communities,” it states.

“The loss of broad protections supporting the medical and often lifesaving procedure of abortions is likely to have a real impact on the maternal mortality rate, especially in those with congenital and/or acquired cardiovascular conditions where evidence-based guidelines advise at times on termination of such high-risk pregnancies.”

The ABC, it states, “believes that every woman, and every person, should be afforded the right to safe, accessible, legal, timely, patient-centered, equitable, and affordable health care.”

The American College of Cardiology (ACC) released a statement on the matter June 24, signed by its president, Edward T.A. Fry, MD, along with five former ACC presidents. “While the ACC has no official policy on abortion, clinical practice guidelines and other clinical guidance tools address the dangers of pregnancy in certain patient populations at higher risk of death or serious cardiac events.”

The college, it states, is “deeply concerned about the potential implications of the Supreme Court decision regarding Roe vs. Wade on the ability of patients and clinicians to engage in important shared discussions about maternal health, or to remove previously available health care options.”

Dr. Bond proposed that a “vocal stance” from medical societies involved in women’s health, “perhaps even a collective stance from our cardiovascular societies and our obstetrics societies,” would also perhaps reach “the masses of doctors in private practice who are dealing with these patients.”

A version of this article first appeared on Medscape.com.

Pregnancy termination for medical reasons had been part of the fabric of everyday health care in the United States since the Supreme Court’s 1973 Roe v. Wade decision, which the current high court overturned in a ruling announced on June 24.

That means many clinicians across specialties are entering uncharted territory with the country’s new patchwork of abortion legality. Some specialties, cardiology among them, may feel the impact more than others.

javi_indy/ Thinkstock

“Unfortunately,” Dr. Haythe said, “many of the states that are going to make or have made abortion illegal are not providing that kind of preconception counseling or good prenatal care to women.”

Cardiologists can provide such counseling to their female patients of childbearing age who have high-risk cardiac conditions, “but not everybody knows that they have a heart problem when they get pregnant, and not everybody is getting screened for heart problems when they’re of childbearing age,” Dr. Haythe said.

“Sometimes it’s not clear whether the problems could have been picked up until a woman is pregnant and has started to have symptoms.” For example, “a lot of women with poor access to health care have rheumatic heart disease. They may have no idea that they have severe aortic stenosis, and it’s not until their second trimester that they start to feel really short of breath.” Often that can be treated in the cath lab, “but again, that’s putting the woman and the baby at risk.”

Cardiologists in states where abortion is illegal will still present the option to their patients with high-risk pregnancies, noted Dr. Haythe. But the conversation may sound something like, “you are at very high risk, termination of the pregnancy takes that risk away, but you’ll have to find a state where it’s legal to do that.”

Dr. Park said such a situation, when abortion is recommended but locally unavailable, is much like any other in cardiology for which the patient may want a second opinion. If a center “doesn’t have the capability or the technology to offer a certain treatment, the patient can opt to seek another opinion at another center,” she said. “Patients will often travel out of state to get the care they need.”

A requirement for out-of-state travel to obtain abortions is likely to worsen socioeconomic disparities in health care, Dr. Bond observed, “because we know that those who are low-income won’t be able to afford that travel.”

Dr. Bond is cosignatory on a statement from the Association of Black Cardiologists (ABC) responding to the high court’s ruling in Dobbs v. Jackson. “This decision will isolate the poor, socioeconomically disadvantaged, and minority populations specifically, widening the already large gaps in health care for our most vulnerable communities,” it states.

“The loss of broad protections supporting the medical and often lifesaving procedure of abortions is likely to have a real impact on the maternal mortality rate, especially in those with congenital and/or acquired cardiovascular conditions where evidence-based guidelines advise at times on termination of such high-risk pregnancies.”

The ABC, it states, “believes that every woman, and every person, should be afforded the right to safe, accessible, legal, timely, patient-centered, equitable, and affordable health care.”

The American College of Cardiology (ACC) released a statement on the matter June 24, signed by its president, Edward T.A. Fry, MD, along with five former ACC presidents. “While the ACC has no official policy on abortion, clinical practice guidelines and other clinical guidance tools address the dangers of pregnancy in certain patient populations at higher risk of death or serious cardiac events.”

The college, it states, is “deeply concerned about the potential implications of the Supreme Court decision regarding Roe vs. Wade on the ability of patients and clinicians to engage in important shared discussions about maternal health, or to remove previously available health care options.”

Dr. Bond proposed that a “vocal stance” from medical societies involved in women’s health, “perhaps even a collective stance from our cardiovascular societies and our obstetrics societies,” would also perhaps reach “the masses of doctors in private practice who are dealing with these patients.”

A version of this article first appeared on Medscape.com.