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The number of drug overdose deaths involving illegally manufactured fentanyl and fentanyl analogs (IMFs) dropped in the United States during the latter portion of 2023. But a new report from the Centers for Disease Control and Prevention (CDC) suggests that an increase in overdoses involving the potent fentanyl analog carfentanil threatens to undo that progress.

Overdose deaths from carfentanil rose by more than 700% in the past year, increasing from 29 between January and June 2023 to 238 in that same period in 2024. 

Carfentanil is used as a tranquilizing agent for elephants and other large mammals and is 100 times more potent than fentanyl. Just 2 mg can be lethal to humans, and a carfentanil-related overdose can require more than three shots of naloxone to reverse.

Prior to this resurgence of carfentanil, the drug “had largely disappeared after carfentanil-involved overdose death outbreaks in 2016-2017,” study authors noted, when carfentanil overdose deaths topped 1200, other data showed.

“Educational and response efforts that can rapidly adapt to the potential for increased distribution of drugs more potent than fentanyl, such as carfentanil, are needed and might avert or mitigate new increases in overdose deaths,” the authors wrote.

The findings were published online in CDC’s Morbidity and Mortality Weekly Report.

 

Carfentanil May Stall Overdose Decline

IMFs such as carfentanil were first detected in the United States illegal drug supply in 2013. A little more than a decade later, IMFs have replaced heroin as the most common opioid in the United States.

The introduction of IMFs led to a sharp rise in overdose deaths, but provisional data suggest these fatalities are on the decline. A recent re-emergence of carfentanil could stall that downward trend.

To investigate further, researchers used data from the CDC’s State Unintentional Drug Overdose Reporting System to analyze detection of IMFs and carfentanil between January 2021 and June 2024. 

The database houses information on drug overdoses obtained from death certificates, coroner and medical examiner reports, and postmortem toxicology reports from 49 states and the District of Columbia.

From January 2021 to December 2023, more than 251,000 people died from drug overdoses with unintentional and undetermined intent, 75% of which involved IMFs. 

IMF-linked deaths peaked at 16,814 in the second quarter of 2023, then declined by nearly 16% to 14,299 deaths by the end of that year.

Investigators could only speculate on the reasons for the decline in overdoses. It is possible that drug users are mixing fentanyl with other drugs, such as xylazine, which may reduce the danger of fatal overdose. It’s also possible that overdose prevention programs are partially responsible for the decline.

“Continued and expanded implementation of these programs, including naloxone distribution and increasing access to treatments for substance use disorders, might result in sustained and continued declines in drug overdose deaths,” they wrote.

 

Regional Differences

When researchers analyzed the results by region, they found that IMFs were detected in 81.5% of overdose deaths in the Northeast, 75% in the Midwest, and 75% in the Southern regions during the study period. These percentages were relatively stable until summer 2023, when declines in IMF-linked overdoses were noteworthy.

Specifically, deaths caused by IMFs decreased 11% in the Northeast (8245 to 7323), 16% in the Midwest (7160 to 6008), and 10.5% in the South (13,492 to 12,077).

In the West, however, overdoses linked to IMFs increased by 66.5% between 2021 and the second quarter of 2024. 

The researchers speculated that the surge in the western United States could be caused by fentanyl entering the drug markets in that region later than in other areas, “likely because of challenges of mixing fentanyl into the black tar heroin that was more common in the West,” they wrote.

The findings suggested that, despite overall declines in overdose deaths reported nationwide, “recent sharp increases in overdose deaths with carfentanil detected, although rare, highlight the ever-changing illegal drug supply and threaten progress in reducing overdose deaths.” 

The report authors encouraged expanding education programs for the public about the dangers of carfentanil and other IMFs, as well as harm reduction strategies, including using fentanyl test strips or drug-checking services.

No study funding information was available. There were no relevant financial relationships.

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

The number of drug overdose deaths involving illegally manufactured fentanyl and fentanyl analogs (IMFs) dropped in the United States during the latter portion of 2023. But a new report from the Centers for Disease Control and Prevention (CDC) suggests that an increase in overdoses involving the potent fentanyl analog carfentanil threatens to undo that progress.

Overdose deaths from carfentanil rose by more than 700% in the past year, increasing from 29 between January and June 2023 to 238 in that same period in 2024. 

Carfentanil is used as a tranquilizing agent for elephants and other large mammals and is 100 times more potent than fentanyl. Just 2 mg can be lethal to humans, and a carfentanil-related overdose can require more than three shots of naloxone to reverse.

Prior to this resurgence of carfentanil, the drug “had largely disappeared after carfentanil-involved overdose death outbreaks in 2016-2017,” study authors noted, when carfentanil overdose deaths topped 1200, other data showed.

“Educational and response efforts that can rapidly adapt to the potential for increased distribution of drugs more potent than fentanyl, such as carfentanil, are needed and might avert or mitigate new increases in overdose deaths,” the authors wrote.

The findings were published online in CDC’s Morbidity and Mortality Weekly Report.

 

Carfentanil May Stall Overdose Decline

IMFs such as carfentanil were first detected in the United States illegal drug supply in 2013. A little more than a decade later, IMFs have replaced heroin as the most common opioid in the United States.

The introduction of IMFs led to a sharp rise in overdose deaths, but provisional data suggest these fatalities are on the decline. A recent re-emergence of carfentanil could stall that downward trend.

To investigate further, researchers used data from the CDC’s State Unintentional Drug Overdose Reporting System to analyze detection of IMFs and carfentanil between January 2021 and June 2024. 

The database houses information on drug overdoses obtained from death certificates, coroner and medical examiner reports, and postmortem toxicology reports from 49 states and the District of Columbia.

From January 2021 to December 2023, more than 251,000 people died from drug overdoses with unintentional and undetermined intent, 75% of which involved IMFs. 

IMF-linked deaths peaked at 16,814 in the second quarter of 2023, then declined by nearly 16% to 14,299 deaths by the end of that year.

Investigators could only speculate on the reasons for the decline in overdoses. It is possible that drug users are mixing fentanyl with other drugs, such as xylazine, which may reduce the danger of fatal overdose. It’s also possible that overdose prevention programs are partially responsible for the decline.

“Continued and expanded implementation of these programs, including naloxone distribution and increasing access to treatments for substance use disorders, might result in sustained and continued declines in drug overdose deaths,” they wrote.

 

Regional Differences

When researchers analyzed the results by region, they found that IMFs were detected in 81.5% of overdose deaths in the Northeast, 75% in the Midwest, and 75% in the Southern regions during the study period. These percentages were relatively stable until summer 2023, when declines in IMF-linked overdoses were noteworthy.

Specifically, deaths caused by IMFs decreased 11% in the Northeast (8245 to 7323), 16% in the Midwest (7160 to 6008), and 10.5% in the South (13,492 to 12,077).

In the West, however, overdoses linked to IMFs increased by 66.5% between 2021 and the second quarter of 2024. 

The researchers speculated that the surge in the western United States could be caused by fentanyl entering the drug markets in that region later than in other areas, “likely because of challenges of mixing fentanyl into the black tar heroin that was more common in the West,” they wrote.

The findings suggested that, despite overall declines in overdose deaths reported nationwide, “recent sharp increases in overdose deaths with carfentanil detected, although rare, highlight the ever-changing illegal drug supply and threaten progress in reducing overdose deaths.” 

The report authors encouraged expanding education programs for the public about the dangers of carfentanil and other IMFs, as well as harm reduction strategies, including using fentanyl test strips or drug-checking services.

No study funding information was available. There were no relevant financial relationships.

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

The number of drug overdose deaths involving illegally manufactured fentanyl and fentanyl analogs (IMFs) dropped in the United States during the latter portion of 2023. But a new report from the Centers for Disease Control and Prevention (CDC) suggests that an increase in overdoses involving the potent fentanyl analog carfentanil threatens to undo that progress.

Overdose deaths from carfentanil rose by more than 700% in the past year, increasing from 29 between January and June 2023 to 238 in that same period in 2024. 

Carfentanil is used as a tranquilizing agent for elephants and other large mammals and is 100 times more potent than fentanyl. Just 2 mg can be lethal to humans, and a carfentanil-related overdose can require more than three shots of naloxone to reverse.

Prior to this resurgence of carfentanil, the drug “had largely disappeared after carfentanil-involved overdose death outbreaks in 2016-2017,” study authors noted, when carfentanil overdose deaths topped 1200, other data showed.

“Educational and response efforts that can rapidly adapt to the potential for increased distribution of drugs more potent than fentanyl, such as carfentanil, are needed and might avert or mitigate new increases in overdose deaths,” the authors wrote.

The findings were published online in CDC’s Morbidity and Mortality Weekly Report.

 

Carfentanil May Stall Overdose Decline

IMFs such as carfentanil were first detected in the United States illegal drug supply in 2013. A little more than a decade later, IMFs have replaced heroin as the most common opioid in the United States.

The introduction of IMFs led to a sharp rise in overdose deaths, but provisional data suggest these fatalities are on the decline. A recent re-emergence of carfentanil could stall that downward trend.

To investigate further, researchers used data from the CDC’s State Unintentional Drug Overdose Reporting System to analyze detection of IMFs and carfentanil between January 2021 and June 2024. 

The database houses information on drug overdoses obtained from death certificates, coroner and medical examiner reports, and postmortem toxicology reports from 49 states and the District of Columbia.

From January 2021 to December 2023, more than 251,000 people died from drug overdoses with unintentional and undetermined intent, 75% of which involved IMFs. 

IMF-linked deaths peaked at 16,814 in the second quarter of 2023, then declined by nearly 16% to 14,299 deaths by the end of that year.

Investigators could only speculate on the reasons for the decline in overdoses. It is possible that drug users are mixing fentanyl with other drugs, such as xylazine, which may reduce the danger of fatal overdose. It’s also possible that overdose prevention programs are partially responsible for the decline.

“Continued and expanded implementation of these programs, including naloxone distribution and increasing access to treatments for substance use disorders, might result in sustained and continued declines in drug overdose deaths,” they wrote.

 

Regional Differences

When researchers analyzed the results by region, they found that IMFs were detected in 81.5% of overdose deaths in the Northeast, 75% in the Midwest, and 75% in the Southern regions during the study period. These percentages were relatively stable until summer 2023, when declines in IMF-linked overdoses were noteworthy.

Specifically, deaths caused by IMFs decreased 11% in the Northeast (8245 to 7323), 16% in the Midwest (7160 to 6008), and 10.5% in the South (13,492 to 12,077).

In the West, however, overdoses linked to IMFs increased by 66.5% between 2021 and the second quarter of 2024. 

The researchers speculated that the surge in the western United States could be caused by fentanyl entering the drug markets in that region later than in other areas, “likely because of challenges of mixing fentanyl into the black tar heroin that was more common in the West,” they wrote.

The findings suggested that, despite overall declines in overdose deaths reported nationwide, “recent sharp increases in overdose deaths with carfentanil detected, although rare, highlight the ever-changing illegal drug supply and threaten progress in reducing overdose deaths.” 

The report authors encouraged expanding education programs for the public about the dangers of carfentanil and other IMFs, as well as harm reduction strategies, including using fentanyl test strips or drug-checking services.

No study funding information was available. There were no relevant financial relationships.

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

This transcript has been edited for clarity. 

I would like to briefly talk about a very interesting paper and one that probably has about as much to inform the doctor-patient relationship as any paper you can think of. 

The title itself gives you a little bit of that answer before I even discuss the outcome. The paper is “The Benefits of Quitting Smoking at Different Ages,” recently published in The American Journal of Preventive Medicine.

I’m not going to even begin to attempt to explore the statistics of the analysis, but I think the conclusions are both fascinating and important. I will read the first sentence of the results and then just comment on some of the others because there’s just so much data here and I really want to focus on the punchline. 

The results section said that, compared with people who never smoked, those who smoke currently, aged 35, 45, 55, 65, or 75, (those were all the groups they looked at), and who have smoked throughout adulthood until that age will lose an average of 9.1, 8.3, 7.3, 5.9, and 4.4 years of life, respectively — obviously, it’s a lot — if they continue to smoke for the rest of their lives. 

If somebody is smoking at age 35 and they continue to smoke, they could lose 9 years of life on average. We know that. It’s terrible. That’s why people should never smoke. Period. End of story. There’s no social value. There’s no health value of smoking. It’s a deadly recreational activity for multiple illnesses, and obviously, cancer is prominent among them.

Here’s the conclusion of the paper that I think is interesting. That doctor, whether it’s a primary care doctor, an oncologist, an ob/gyn, or a family doctor, is seeing Mr Smith or Mrs Jones in the office today, whether they know that patient well or not very well, and they’re still smoking. However, if the person we’re describing here quits smoking at these ages, how much life do they add back, compared with if they continued?

They may say: “Oh, I’ve been smoking all my life. What difference does it make? The die is cast.” Wrong! If you’ve been smoking your whole adult life — so let’s just say that you started at age 18, age 20, age 15, or even age 12 — but you quit smoking at the age of 35, you’re going to add 8 years of life on average. If you quit smoking when you’re 65, having smoked your whole adult life, you will add 1.7 years of life. That’s 1.7 years to be with your family, to be with your grandchildren, and enjoy life. If you ask, “Oh, what difference does it make?” It makes a big difference. 

I’ll share another statistic and I’ll be done. I think this is really an interesting one. The chances of gaining at least a year of life among those who quit smoking at the age of 65 was 23.4%. There is a 1 out of 4 chance that you’re going to live an additional year if you stop at age 65. Even if you stop smoking at age 75, you have a 14% chance of living at least an additional year longer than you would have if you didn’t stop smoking. 

There is much to think about here, much to consider, and much to discuss potentially with patients.

Dr. Markman is Professor of Medical Oncology and Therapeutics Research, City of Hope Comprehensive Cancer Center; President, Medicine & Science, City of Hope Atlanta, Chicago, Phoenix. He reported conflicts of interest with GlaxoSmithKline and AstraZeneca.

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

This transcript has been edited for clarity. 

I would like to briefly talk about a very interesting paper and one that probably has about as much to inform the doctor-patient relationship as any paper you can think of. 

The title itself gives you a little bit of that answer before I even discuss the outcome. The paper is “The Benefits of Quitting Smoking at Different Ages,” recently published in The American Journal of Preventive Medicine.

I’m not going to even begin to attempt to explore the statistics of the analysis, but I think the conclusions are both fascinating and important. I will read the first sentence of the results and then just comment on some of the others because there’s just so much data here and I really want to focus on the punchline. 

The results section said that, compared with people who never smoked, those who smoke currently, aged 35, 45, 55, 65, or 75, (those were all the groups they looked at), and who have smoked throughout adulthood until that age will lose an average of 9.1, 8.3, 7.3, 5.9, and 4.4 years of life, respectively — obviously, it’s a lot — if they continue to smoke for the rest of their lives. 

If somebody is smoking at age 35 and they continue to smoke, they could lose 9 years of life on average. We know that. It’s terrible. That’s why people should never smoke. Period. End of story. There’s no social value. There’s no health value of smoking. It’s a deadly recreational activity for multiple illnesses, and obviously, cancer is prominent among them.

Here’s the conclusion of the paper that I think is interesting. That doctor, whether it’s a primary care doctor, an oncologist, an ob/gyn, or a family doctor, is seeing Mr Smith or Mrs Jones in the office today, whether they know that patient well or not very well, and they’re still smoking. However, if the person we’re describing here quits smoking at these ages, how much life do they add back, compared with if they continued?

They may say: “Oh, I’ve been smoking all my life. What difference does it make? The die is cast.” Wrong! If you’ve been smoking your whole adult life — so let’s just say that you started at age 18, age 20, age 15, or even age 12 — but you quit smoking at the age of 35, you’re going to add 8 years of life on average. If you quit smoking when you’re 65, having smoked your whole adult life, you will add 1.7 years of life. That’s 1.7 years to be with your family, to be with your grandchildren, and enjoy life. If you ask, “Oh, what difference does it make?” It makes a big difference. 

I’ll share another statistic and I’ll be done. I think this is really an interesting one. The chances of gaining at least a year of life among those who quit smoking at the age of 65 was 23.4%. There is a 1 out of 4 chance that you’re going to live an additional year if you stop at age 65. Even if you stop smoking at age 75, you have a 14% chance of living at least an additional year longer than you would have if you didn’t stop smoking. 

There is much to think about here, much to consider, and much to discuss potentially with patients.

Dr. Markman is Professor of Medical Oncology and Therapeutics Research, City of Hope Comprehensive Cancer Center; President, Medicine & Science, City of Hope Atlanta, Chicago, Phoenix. He reported conflicts of interest with GlaxoSmithKline and AstraZeneca.

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

This transcript has been edited for clarity. 

I would like to briefly talk about a very interesting paper and one that probably has about as much to inform the doctor-patient relationship as any paper you can think of. 

The title itself gives you a little bit of that answer before I even discuss the outcome. The paper is “The Benefits of Quitting Smoking at Different Ages,” recently published in The American Journal of Preventive Medicine.

I’m not going to even begin to attempt to explore the statistics of the analysis, but I think the conclusions are both fascinating and important. I will read the first sentence of the results and then just comment on some of the others because there’s just so much data here and I really want to focus on the punchline. 

The results section said that, compared with people who never smoked, those who smoke currently, aged 35, 45, 55, 65, or 75, (those were all the groups they looked at), and who have smoked throughout adulthood until that age will lose an average of 9.1, 8.3, 7.3, 5.9, and 4.4 years of life, respectively — obviously, it’s a lot — if they continue to smoke for the rest of their lives. 

If somebody is smoking at age 35 and they continue to smoke, they could lose 9 years of life on average. We know that. It’s terrible. That’s why people should never smoke. Period. End of story. There’s no social value. There’s no health value of smoking. It’s a deadly recreational activity for multiple illnesses, and obviously, cancer is prominent among them.

Here’s the conclusion of the paper that I think is interesting. That doctor, whether it’s a primary care doctor, an oncologist, an ob/gyn, or a family doctor, is seeing Mr Smith or Mrs Jones in the office today, whether they know that patient well or not very well, and they’re still smoking. However, if the person we’re describing here quits smoking at these ages, how much life do they add back, compared with if they continued?

They may say: “Oh, I’ve been smoking all my life. What difference does it make? The die is cast.” Wrong! If you’ve been smoking your whole adult life — so let’s just say that you started at age 18, age 20, age 15, or even age 12 — but you quit smoking at the age of 35, you’re going to add 8 years of life on average. If you quit smoking when you’re 65, having smoked your whole adult life, you will add 1.7 years of life. That’s 1.7 years to be with your family, to be with your grandchildren, and enjoy life. If you ask, “Oh, what difference does it make?” It makes a big difference. 

I’ll share another statistic and I’ll be done. I think this is really an interesting one. The chances of gaining at least a year of life among those who quit smoking at the age of 65 was 23.4%. There is a 1 out of 4 chance that you’re going to live an additional year if you stop at age 65. Even if you stop smoking at age 75, you have a 14% chance of living at least an additional year longer than you would have if you didn’t stop smoking. 

There is much to think about here, much to consider, and much to discuss potentially with patients.

Dr. Markman is Professor of Medical Oncology and Therapeutics Research, City of Hope Comprehensive Cancer Center; President, Medicine & Science, City of Hope Atlanta, Chicago, Phoenix. He reported conflicts of interest with GlaxoSmithKline and AstraZeneca.

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

TOPLINE:

A new telephone-based program implemented in a Federally Qualified Health Center (FQHC) demonstrates effectiveness in reducing unhealthy alcohol use among diverse adult patients screened using the Alcohol Use Disorders Identification Test (AUDIT).

METHODOLOGY:

• Researchers implemented a screening and team-based telephonic program within a large FQHC system in Texas in which adult patients were routinely screened using AUDIT-Consumption (AUDIT-C) questions.
• The team-based, telecare-centered program was designed to follow-up positive screening results with full AUDIT assessments and to provide a two-session brief intervention for all patients. Patients with AUDIT scores ≥ 12 received the brief intervention along with a referral for additional support or an assessment for pharmacotherapy prescription.
• The researchers screened 3959 patients between March 2021 and May 2023, of whom 412 patients with positive results were successfully contacted and had their AUDIT completed (mean age, 46 years; 32% women; 86% Hispanic/Latino; 65% preferred Spanish).
• Of these, 29 patients had full AUDIT scores ranging from 0 to 3, 252 had scores between 4 and 12, and 131 had scores > 12.
• Follow-up AUDIT assessments conducted at 3-6 months were completed for 251 patients (26% women; 90% Hispanic/Latino), and those with AUDIT scores ≥ 12 were offered additional treatment options, including telecare services, in-person appointments with the addiction medicine clinic, and/or pharmacotherapy.

TAKEAWAY:

• Among the patients with an initial AUDIT score > 12, 19 received pharmacotherapy and 13 had at least one appointment with the addiction medicine service.
• For patients who completed the initial and final follow-ups, the mean change in AUDIT score was −4.1 (95% CI, −3.4 to −4.7).
• Spanish-speaking patients demonstrated a greater reduction in AUDIT scores than English-speaking patients.
• The mean reduction in the AUDIT score at the 3- to 6-month follow-up was larger in those with initial AUDIT scores > 12 than in those with initial AUDIT scores ≤ 12 (7.99 vs 2.25).

IN PRACTICE:

“Our intervention was delivered outside of traditional office visits and did not disrupt clinic flow or add burden to the practice’s providers, who already face significant challenges in serving this high-needs population,” the authors wrote. “We believe this program offers a template for delivering evidence-based, equitable preventive care for unhealthy alcohol use in a diverse patient population.”

SOURCE:

The study was led by Michael Pignone, MD, MPH, Department of Medicine, Duke University School of Medicine, Durham, North Carolina. It was published online in the Journal of General Internal Medicine.

LIMITATIONS:

The lack of systematic tracking for the unsuccessful attempts at establishing contact limited the understanding of the variations in screening positivity and the subsequent engagement in the program. Program staffing and constraints in the budget limited the ability to reach all potentially interested participants. The absence of a control group made it difficult to attribute the observed reductions in the AUDIT scores solely to the intervention. The data on follow-up were collected from only 61% participants, raising the possibility that those who were not reached may have had different outcomes than those who were successfully contacted.

DISCLOSURES:

The Cancer Prevention and Research Institute of Texas provided funding for this program. The authors reported no conflicts of interest.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article first appeared on Medscape.com.

TOPLINE:

A new telephone-based program implemented in a Federally Qualified Health Center (FQHC) demonstrates effectiveness in reducing unhealthy alcohol use among diverse adult patients screened using the Alcohol Use Disorders Identification Test (AUDIT).

METHODOLOGY:

• Researchers implemented a screening and team-based telephonic program within a large FQHC system in Texas in which adult patients were routinely screened using AUDIT-Consumption (AUDIT-C) questions.
• The team-based, telecare-centered program was designed to follow-up positive screening results with full AUDIT assessments and to provide a two-session brief intervention for all patients. Patients with AUDIT scores ≥ 12 received the brief intervention along with a referral for additional support or an assessment for pharmacotherapy prescription.
• The researchers screened 3959 patients between March 2021 and May 2023, of whom 412 patients with positive results were successfully contacted and had their AUDIT completed (mean age, 46 years; 32% women; 86% Hispanic/Latino; 65% preferred Spanish).
• Of these, 29 patients had full AUDIT scores ranging from 0 to 3, 252 had scores between 4 and 12, and 131 had scores > 12.
• Follow-up AUDIT assessments conducted at 3-6 months were completed for 251 patients (26% women; 90% Hispanic/Latino), and those with AUDIT scores ≥ 12 were offered additional treatment options, including telecare services, in-person appointments with the addiction medicine clinic, and/or pharmacotherapy.

TAKEAWAY:

• Among the patients with an initial AUDIT score > 12, 19 received pharmacotherapy and 13 had at least one appointment with the addiction medicine service.
• For patients who completed the initial and final follow-ups, the mean change in AUDIT score was −4.1 (95% CI, −3.4 to −4.7).
• Spanish-speaking patients demonstrated a greater reduction in AUDIT scores than English-speaking patients.
• The mean reduction in the AUDIT score at the 3- to 6-month follow-up was larger in those with initial AUDIT scores > 12 than in those with initial AUDIT scores ≤ 12 (7.99 vs 2.25).

IN PRACTICE:

“Our intervention was delivered outside of traditional office visits and did not disrupt clinic flow or add burden to the practice’s providers, who already face significant challenges in serving this high-needs population,” the authors wrote. “We believe this program offers a template for delivering evidence-based, equitable preventive care for unhealthy alcohol use in a diverse patient population.”

SOURCE:

The study was led by Michael Pignone, MD, MPH, Department of Medicine, Duke University School of Medicine, Durham, North Carolina. It was published online in the Journal of General Internal Medicine.

LIMITATIONS:

The lack of systematic tracking for the unsuccessful attempts at establishing contact limited the understanding of the variations in screening positivity and the subsequent engagement in the program. Program staffing and constraints in the budget limited the ability to reach all potentially interested participants. The absence of a control group made it difficult to attribute the observed reductions in the AUDIT scores solely to the intervention. The data on follow-up were collected from only 61% participants, raising the possibility that those who were not reached may have had different outcomes than those who were successfully contacted.

DISCLOSURES:

The Cancer Prevention and Research Institute of Texas provided funding for this program. The authors reported no conflicts of interest.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article first appeared on Medscape.com.

TOPLINE:

A new telephone-based program implemented in a Federally Qualified Health Center (FQHC) demonstrates effectiveness in reducing unhealthy alcohol use among diverse adult patients screened using the Alcohol Use Disorders Identification Test (AUDIT).

METHODOLOGY:

• Researchers implemented a screening and team-based telephonic program within a large FQHC system in Texas in which adult patients were routinely screened using AUDIT-Consumption (AUDIT-C) questions.
• The team-based, telecare-centered program was designed to follow-up positive screening results with full AUDIT assessments and to provide a two-session brief intervention for all patients. Patients with AUDIT scores ≥ 12 received the brief intervention along with a referral for additional support or an assessment for pharmacotherapy prescription.
• The researchers screened 3959 patients between March 2021 and May 2023, of whom 412 patients with positive results were successfully contacted and had their AUDIT completed (mean age, 46 years; 32% women; 86% Hispanic/Latino; 65% preferred Spanish).
• Of these, 29 patients had full AUDIT scores ranging from 0 to 3, 252 had scores between 4 and 12, and 131 had scores > 12.
• Follow-up AUDIT assessments conducted at 3-6 months were completed for 251 patients (26% women; 90% Hispanic/Latino), and those with AUDIT scores ≥ 12 were offered additional treatment options, including telecare services, in-person appointments with the addiction medicine clinic, and/or pharmacotherapy.

TAKEAWAY:

• Among the patients with an initial AUDIT score > 12, 19 received pharmacotherapy and 13 had at least one appointment with the addiction medicine service.
• For patients who completed the initial and final follow-ups, the mean change in AUDIT score was −4.1 (95% CI, −3.4 to −4.7).
• Spanish-speaking patients demonstrated a greater reduction in AUDIT scores than English-speaking patients.
• The mean reduction in the AUDIT score at the 3- to 6-month follow-up was larger in those with initial AUDIT scores > 12 than in those with initial AUDIT scores ≤ 12 (7.99 vs 2.25).

IN PRACTICE:

“Our intervention was delivered outside of traditional office visits and did not disrupt clinic flow or add burden to the practice’s providers, who already face significant challenges in serving this high-needs population,” the authors wrote. “We believe this program offers a template for delivering evidence-based, equitable preventive care for unhealthy alcohol use in a diverse patient population.”

SOURCE:

The study was led by Michael Pignone, MD, MPH, Department of Medicine, Duke University School of Medicine, Durham, North Carolina. It was published online in the Journal of General Internal Medicine.

LIMITATIONS:

The lack of systematic tracking for the unsuccessful attempts at establishing contact limited the understanding of the variations in screening positivity and the subsequent engagement in the program. Program staffing and constraints in the budget limited the ability to reach all potentially interested participants. The absence of a control group made it difficult to attribute the observed reductions in the AUDIT scores solely to the intervention. The data on follow-up were collected from only 61% participants, raising the possibility that those who were not reached may have had different outcomes than those who were successfully contacted.

DISCLOSURES:

The Cancer Prevention and Research Institute of Texas provided funding for this program. The authors reported no conflicts of interest.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article first appeared on Medscape.com.

The Food and Drug Administration (FDA) has approved ustekinumab-stba (Steqeyma) as a biosimilar to the interleukin-12 and -23 inhibitor ustekinumab (Stelara) for the treatment of adults with active Crohn’s disease or ulcerative colitis and for both children aged ≥ 6 years and adults with moderate to severe plaque psoriasis or active psoriatic arthritis.

This is the seventh ustekinumab biosimilar approved by the FDA. The biosimilar, developed by Celltrion, has a license entry date in February 2025 as part of the settlement and license agreement with the manufacturer of the reference biologic, Johnson & Johnson.

Ustekinumab-stba will be available in two formulations: A subcutaneous injection in two strengths — a 45 mg/0.5 mL or 90 mg/1 mL solution in a single-dose, prefilled syringe — and an intravenous infusion of a 130 mg/26 mL (5 mg/mL) solution in a single-dose vial.

“The approval of Steqeyma reflects Celltrion’s continued investment in providing treatment options to patients diagnosed with ulcerative colitis, Crohn’s disease, psoriasis, and psoriatic arthritis,” said Thomas Nusbickel, Chief Commercial Officer at Celltrion USA, Jersey City, New Jersey, in a press release.

The FDA has previously approved the company’s adalimumab biosimilar Yuflyma and its infliximab biosimilar Zymfentra.

The full prescribing information for ustekinumab-stba is available here.

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

The Food and Drug Administration (FDA) has approved ustekinumab-stba (Steqeyma) as a biosimilar to the interleukin-12 and -23 inhibitor ustekinumab (Stelara) for the treatment of adults with active Crohn’s disease or ulcerative colitis and for both children aged ≥ 6 years and adults with moderate to severe plaque psoriasis or active psoriatic arthritis.

This is the seventh ustekinumab biosimilar approved by the FDA. The biosimilar, developed by Celltrion, has a license entry date in February 2025 as part of the settlement and license agreement with the manufacturer of the reference biologic, Johnson & Johnson.

Ustekinumab-stba will be available in two formulations: A subcutaneous injection in two strengths — a 45 mg/0.5 mL or 90 mg/1 mL solution in a single-dose, prefilled syringe — and an intravenous infusion of a 130 mg/26 mL (5 mg/mL) solution in a single-dose vial.

“The approval of Steqeyma reflects Celltrion’s continued investment in providing treatment options to patients diagnosed with ulcerative colitis, Crohn’s disease, psoriasis, and psoriatic arthritis,” said Thomas Nusbickel, Chief Commercial Officer at Celltrion USA, Jersey City, New Jersey, in a press release.

The FDA has previously approved the company’s adalimumab biosimilar Yuflyma and its infliximab biosimilar Zymfentra.

The full prescribing information for ustekinumab-stba is available here.

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

The Food and Drug Administration (FDA) has approved ustekinumab-stba (Steqeyma) as a biosimilar to the interleukin-12 and -23 inhibitor ustekinumab (Stelara) for the treatment of adults with active Crohn’s disease or ulcerative colitis and for both children aged ≥ 6 years and adults with moderate to severe plaque psoriasis or active psoriatic arthritis.

This is the seventh ustekinumab biosimilar approved by the FDA. The biosimilar, developed by Celltrion, has a license entry date in February 2025 as part of the settlement and license agreement with the manufacturer of the reference biologic, Johnson & Johnson.

Ustekinumab-stba will be available in two formulations: A subcutaneous injection in two strengths — a 45 mg/0.5 mL or 90 mg/1 mL solution in a single-dose, prefilled syringe — and an intravenous infusion of a 130 mg/26 mL (5 mg/mL) solution in a single-dose vial.

“The approval of Steqeyma reflects Celltrion’s continued investment in providing treatment options to patients diagnosed with ulcerative colitis, Crohn’s disease, psoriasis, and psoriatic arthritis,” said Thomas Nusbickel, Chief Commercial Officer at Celltrion USA, Jersey City, New Jersey, in a press release.

The FDA has previously approved the company’s adalimumab biosimilar Yuflyma and its infliximab biosimilar Zymfentra.

The full prescribing information for ustekinumab-stba is available here.

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

OVIEDO, SPAIN – In April 2023, the Navarra Pharmacovigilance Center (NPC) became aware of a case involving an infant who developed progressive hair growth on their back, legs, and thighs (hypertrichosis) over the course of 2 months. During an interview with the family, it was revealed that the infant’s father had been using 5% topical minoxidil to treat androgenic alopecia, and he had taken a leave of absence from work to care for his child. After the medication was discontinued, the infant’s symptoms fully regressed. Specialists from the NPC presented the case at the 13th Spanish Pharmacovigilance Congress in November 2024.

A review of similar cases reported in the Spanish Pharmacovigilance System database identified six additional cases with the same characteristics, all involving infants whose caregivers were using minoxidil. Four more cases were found through the European pharmacovigilance database EudraVigilance and a review of scientific literature, bringing the total to 11 cases.

According to the Navarra Pharmacovigilance Bulletin, these cases are concerning as they highlight the exposure of vulnerable infants to a medication not indicated for their age group. Additionally, the condition can cause significant stress for the families of the affected children.

 

Mechanism of Transmission Unclear

The exact mechanism by which caregivers transfer minoxidil to infants is not fully understood. In the newly identified cases, specialists suspect the drug was transmitted through direct or indirect contact. Accidental ingestion is also a possibility if the infant’s hands touched treated areas on the caregiver’s skin and were then brought to the mouth.

The NPC explained that infants’ skin is more permeable because of the thinner stratum corneum and a higher surface area/body weight ratio, making them more susceptible to absorbing topically applied medications.

 

Regulatory Changes and Precautions

In light of these findings, the European Medicines Agency’s Pharmacovigilance Risk Assessment Committee concluded that, starting in October 2024, product information for medications containing minoxidil should be updated. Specifically, new information must be added to the package insert warning about the risk for hypertrichosis in infants following accidental exposure to minoxidil.

The NPC emphasizes the importance of caregivers being aware of the risks associated with topical medications like minoxidil. Recommended precautions include thoroughly washing hands after applying the product and covering treated areas to prevent direct contact with infants’ skin.

Healthcare professionals should also be aware of this risk and consider it when diagnosing hypertrichosis in infants. Recognizing the connection can prevent unnecessary testing for the infant and alleviate stress for the family.

This story was translated from Univadis Spain using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article appeared on Medscape.com.

OVIEDO, SPAIN – In April 2023, the Navarra Pharmacovigilance Center (NPC) became aware of a case involving an infant who developed progressive hair growth on their back, legs, and thighs (hypertrichosis) over the course of 2 months. During an interview with the family, it was revealed that the infant’s father had been using 5% topical minoxidil to treat androgenic alopecia, and he had taken a leave of absence from work to care for his child. After the medication was discontinued, the infant’s symptoms fully regressed. Specialists from the NPC presented the case at the 13th Spanish Pharmacovigilance Congress in November 2024.

A review of similar cases reported in the Spanish Pharmacovigilance System database identified six additional cases with the same characteristics, all involving infants whose caregivers were using minoxidil. Four more cases were found through the European pharmacovigilance database EudraVigilance and a review of scientific literature, bringing the total to 11 cases.

According to the Navarra Pharmacovigilance Bulletin, these cases are concerning as they highlight the exposure of vulnerable infants to a medication not indicated for their age group. Additionally, the condition can cause significant stress for the families of the affected children.

 

Mechanism of Transmission Unclear

The exact mechanism by which caregivers transfer minoxidil to infants is not fully understood. In the newly identified cases, specialists suspect the drug was transmitted through direct or indirect contact. Accidental ingestion is also a possibility if the infant’s hands touched treated areas on the caregiver’s skin and were then brought to the mouth.

The NPC explained that infants’ skin is more permeable because of the thinner stratum corneum and a higher surface area/body weight ratio, making them more susceptible to absorbing topically applied medications.

 

Regulatory Changes and Precautions

In light of these findings, the European Medicines Agency’s Pharmacovigilance Risk Assessment Committee concluded that, starting in October 2024, product information for medications containing minoxidil should be updated. Specifically, new information must be added to the package insert warning about the risk for hypertrichosis in infants following accidental exposure to minoxidil.

The NPC emphasizes the importance of caregivers being aware of the risks associated with topical medications like minoxidil. Recommended precautions include thoroughly washing hands after applying the product and covering treated areas to prevent direct contact with infants’ skin.

Healthcare professionals should also be aware of this risk and consider it when diagnosing hypertrichosis in infants. Recognizing the connection can prevent unnecessary testing for the infant and alleviate stress for the family.

This story was translated from Univadis Spain using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article appeared on Medscape.com.

OVIEDO, SPAIN – In April 2023, the Navarra Pharmacovigilance Center (NPC) became aware of a case involving an infant who developed progressive hair growth on their back, legs, and thighs (hypertrichosis) over the course of 2 months. During an interview with the family, it was revealed that the infant’s father had been using 5% topical minoxidil to treat androgenic alopecia, and he had taken a leave of absence from work to care for his child. After the medication was discontinued, the infant’s symptoms fully regressed. Specialists from the NPC presented the case at the 13th Spanish Pharmacovigilance Congress in November 2024.

A review of similar cases reported in the Spanish Pharmacovigilance System database identified six additional cases with the same characteristics, all involving infants whose caregivers were using minoxidil. Four more cases were found through the European pharmacovigilance database EudraVigilance and a review of scientific literature, bringing the total to 11 cases.

According to the Navarra Pharmacovigilance Bulletin, these cases are concerning as they highlight the exposure of vulnerable infants to a medication not indicated for their age group. Additionally, the condition can cause significant stress for the families of the affected children.

 

Mechanism of Transmission Unclear

The exact mechanism by which caregivers transfer minoxidil to infants is not fully understood. In the newly identified cases, specialists suspect the drug was transmitted through direct or indirect contact. Accidental ingestion is also a possibility if the infant’s hands touched treated areas on the caregiver’s skin and were then brought to the mouth.

The NPC explained that infants’ skin is more permeable because of the thinner stratum corneum and a higher surface area/body weight ratio, making them more susceptible to absorbing topically applied medications.

 

Regulatory Changes and Precautions

In light of these findings, the European Medicines Agency’s Pharmacovigilance Risk Assessment Committee concluded that, starting in October 2024, product information for medications containing minoxidil should be updated. Specifically, new information must be added to the package insert warning about the risk for hypertrichosis in infants following accidental exposure to minoxidil.

The NPC emphasizes the importance of caregivers being aware of the risks associated with topical medications like minoxidil. Recommended precautions include thoroughly washing hands after applying the product and covering treated areas to prevent direct contact with infants’ skin.

Healthcare professionals should also be aware of this risk and consider it when diagnosing hypertrichosis in infants. Recognizing the connection can prevent unnecessary testing for the infant and alleviate stress for the family.

This story was translated from Univadis Spain using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article appeared on Medscape.com.

Alpha-gal syndrome (AGS), a tickborne disease commonly called “red meat allergy,” is a serious, potentially life-threatening allergy to the carbohydrate alpha-gal. The alpha-gal carbohydrate is found in most mammals, though it is not in humans, apes, or old-world monkeys. People with AGS can have allergic reactions when they consume mammalian meat, dairy products, or other products derived from mammals. People often live with this disease for years before receiving a correct diagnosis, greatly impacting their quality of life. The number of suspected cases is also rising. 

More than 110,000 suspected AGS cases were identified between 2010 and 2022, according to a Centers for Disease Control and Prevention (CDC) report.¹ However, because the diagnosis requires a positive test and a clinical exam and some people may not get tested, as many as 450,000 people might be affected by AGS in the United States. Additionally, a CDC survey found that nearly half (42%) of US healthcare providers had never heard of AGS.² Among those who had, less than one third (29%) knew how to diagnose the condition. 

Here are 5 things clinicians need to know about AGS.

 

1. People can develop AGS after being bitten by a tick, primarily the lone star tick (Amblyomma americanum), in the United States.

In the United States, AGS is primarily associated with the bite of a lone star tick, but other kinds of ticks have not been ruled out. The majority of suspected AGS cases in the United States were reported in parts of Arkansas, Delaware, Illinois, Indiana, Kansas, Kentucky, Maryland, Mississippi, Missouri, North Carolina, Oklahoma, Tennessee, and Virginia. The lone star tick is widely distributed with established populations in Alabama, Arkansas, Connecticut, Delaware, Florida, Georgia, Illinois, Indiana, Iowa, Kansas, Kentucky, Louisiana, Michigan, Minnesota, Mississippi, Missouri, Nebraska, New Hampshire, New Jersey, New York, North Carolina, Ohio, Oklahoma, Pennsylvania, South Carolina, Tennessee, Texas, Virginia, and West Virginia. 

While AGS is associated with tick bites, more research is needed to understand the role ticks play in starting this condition, and why certain people develop AGS. Anyone can develop AGS, but most cases have been reported in adults. 

Know how to recognize the symptoms of AGS and be prepared to test, diagnose, and manage AGS, particularly in states where lone star ticks are found. 

 

2. Tick bites are only one risk factor for developing AGS. 

Many people are bitten by lone star ticks and will never develop AGS. Scientists are exploring the connection between other risk factors and developing AGS. A recent study has shown that people diagnosed with AGS may be more likely to have a family member who was also diagnosed with AGS, have another food allergy, have an allergy to stinging or biting insects, or have A or O blood types.³ 

Research has also shown that environmental risk factors could contribute to developing AGS,⁴ like living in an area with lone star ticks, remembering finding a tick on themselves, recalling multiple tick bites, living near a wooded forest, spending more time outside, or living in areas with deer, such as larger properties, wooded forests, and properties with shrubs and brush. 

Ask your patient questions about other allergies and history of recent tick bites or outdoor exposure to help determine if testing for AGS is appropriate.

 

3. Symptoms of AGS are consistently inconsistent.

There is a spectrum of how sensitive AGS patients are to alpha-gal, and reactions are often different from person to person, which can make it difficult to diagnose. The first allergic reaction to AGS typically occurs between 1-6 months after a tick bite. Symptoms commonly appear 2-6 hours after being in contact with products containing alpha-gal, like red meat (beef, pork, lamb, venison, rabbit, or other meat from mammals), dairy, and some medications. Symptoms can range from mild to severe and include hives or itchy rash; swelling of the lips, throat, tongue, or eyelids; gastrointestinal symptoms such as nausea, vomiting, or diarrhea; heartburn or indigestion; cough, shortness of breath, or difficulty breathing; dizziness or a drop in blood pressure; or anaphylaxis.

Consider AGS if a patient reports waking up in the middle of the night with allergic symptoms after eating alpha-gal containing products for dinner, if allergic reactions are delayed, or if a patient has anaphylaxis of unknown cause, adult-onset allergy, or allergic symptoms and reports a recent tick bite. 

 

4. Diagnosing AGS requires a combination of a blood test and a physical exam.

Diagnosing AGS requires a detailed patient history, physical exam, and a blood test to detect specific immunoglobulin E (IgE) antibodies specific to alpha-gal (alpha-gal sIgE). Tests for alpha-gal sIgE antibodies are available at several large commercial laboratories and some academic institutions. Skin tests to identify reactions to allergens like pork or beef may also be used to inform AGS diagnosis. However, a positive alpha-gal sIgE test or skin test does not mean a person has AGS. Many people, particularly those who live in regions with lone star ticks, have positive alpha-gal specific IgE tests without having AGS. 

Consider the test results along with your patient’s symptoms and risk factors.

 

5. There is no treatment for AGS, but people can take prevention steps and AGS can be managed.

People can protect themselves and their family from AGS by preventing tick bites. Encourage your patients to use an Environmental Protection Agency–registered insect repellent outdoors, wear permethrin-treated clothing, and conduct thorough tick checks after outdoor activities. 

Once a person is no longer exposed to alpha-gal containing products, they should no longer experience symptoms. People with AGS should also proactively prevent tick bites. Tick bites can trigger or reactivate AGS.

For patients who have AGS, help manage their symptoms and identify alpha-gal containing products to avoid.

Dr. Kersh is Chief of the Rickettsial Zoonoses Branch, Division of Vector-Borne Diseases, Centers for Disease Control and Prevention, Atlanta, Georgia, and disclosed no relevant conflicts of interest.

CDC resources:

About Alpha-gal Syndrome | Alpha-gal Syndrome | CDC 

Clinical Testing and Diagnosis for Alpha-gal Syndrome | Alpha-gal Syndrome | CDC 

Clinical Resources | Alpha-gal Syndrome | CDC 

References 

Thompson JM et al. MMWR Morb Mortal Wkly Rep. 2023;72:815-820. 

Carpenter A et al. MMWR Morb Mortal Wkly Rep. 2023;72:809-814. Taylor ML et al. Ann Allergy, Asthma & Immunol. 2024 Jun;132(6):759.e2-764.e2. Kersh GJ et al. Ann Allergy, Asthma & Immunol. 2023 Apr;130(4):472-478.

Alpha-gal syndrome (AGS), a tickborne disease commonly called “red meat allergy,” is a serious, potentially life-threatening allergy to the carbohydrate alpha-gal. The alpha-gal carbohydrate is found in most mammals, though it is not in humans, apes, or old-world monkeys. People with AGS can have allergic reactions when they consume mammalian meat, dairy products, or other products derived from mammals. People often live with this disease for years before receiving a correct diagnosis, greatly impacting their quality of life. The number of suspected cases is also rising. 

More than 110,000 suspected AGS cases were identified between 2010 and 2022, according to a Centers for Disease Control and Prevention (CDC) report.¹ However, because the diagnosis requires a positive test and a clinical exam and some people may not get tested, as many as 450,000 people might be affected by AGS in the United States. Additionally, a CDC survey found that nearly half (42%) of US healthcare providers had never heard of AGS.² Among those who had, less than one third (29%) knew how to diagnose the condition. 

Here are 5 things clinicians need to know about AGS.

 

1. People can develop AGS after being bitten by a tick, primarily the lone star tick (Amblyomma americanum), in the United States.

In the United States, AGS is primarily associated with the bite of a lone star tick, but other kinds of ticks have not been ruled out. The majority of suspected AGS cases in the United States were reported in parts of Arkansas, Delaware, Illinois, Indiana, Kansas, Kentucky, Maryland, Mississippi, Missouri, North Carolina, Oklahoma, Tennessee, and Virginia. The lone star tick is widely distributed with established populations in Alabama, Arkansas, Connecticut, Delaware, Florida, Georgia, Illinois, Indiana, Iowa, Kansas, Kentucky, Louisiana, Michigan, Minnesota, Mississippi, Missouri, Nebraska, New Hampshire, New Jersey, New York, North Carolina, Ohio, Oklahoma, Pennsylvania, South Carolina, Tennessee, Texas, Virginia, and West Virginia. 

While AGS is associated with tick bites, more research is needed to understand the role ticks play in starting this condition, and why certain people develop AGS. Anyone can develop AGS, but most cases have been reported in adults. 

Know how to recognize the symptoms of AGS and be prepared to test, diagnose, and manage AGS, particularly in states where lone star ticks are found. 

 

2. Tick bites are only one risk factor for developing AGS. 

Many people are bitten by lone star ticks and will never develop AGS. Scientists are exploring the connection between other risk factors and developing AGS. A recent study has shown that people diagnosed with AGS may be more likely to have a family member who was also diagnosed with AGS, have another food allergy, have an allergy to stinging or biting insects, or have A or O blood types.³ 

Research has also shown that environmental risk factors could contribute to developing AGS,⁴ like living in an area with lone star ticks, remembering finding a tick on themselves, recalling multiple tick bites, living near a wooded forest, spending more time outside, or living in areas with deer, such as larger properties, wooded forests, and properties with shrubs and brush. 

Ask your patient questions about other allergies and history of recent tick bites or outdoor exposure to help determine if testing for AGS is appropriate.

 

3. Symptoms of AGS are consistently inconsistent.

There is a spectrum of how sensitive AGS patients are to alpha-gal, and reactions are often different from person to person, which can make it difficult to diagnose. The first allergic reaction to AGS typically occurs between 1-6 months after a tick bite. Symptoms commonly appear 2-6 hours after being in contact with products containing alpha-gal, like red meat (beef, pork, lamb, venison, rabbit, or other meat from mammals), dairy, and some medications. Symptoms can range from mild to severe and include hives or itchy rash; swelling of the lips, throat, tongue, or eyelids; gastrointestinal symptoms such as nausea, vomiting, or diarrhea; heartburn or indigestion; cough, shortness of breath, or difficulty breathing; dizziness or a drop in blood pressure; or anaphylaxis.

Consider AGS if a patient reports waking up in the middle of the night with allergic symptoms after eating alpha-gal containing products for dinner, if allergic reactions are delayed, or if a patient has anaphylaxis of unknown cause, adult-onset allergy, or allergic symptoms and reports a recent tick bite. 

 

4. Diagnosing AGS requires a combination of a blood test and a physical exam.

Diagnosing AGS requires a detailed patient history, physical exam, and a blood test to detect specific immunoglobulin E (IgE) antibodies specific to alpha-gal (alpha-gal sIgE). Tests for alpha-gal sIgE antibodies are available at several large commercial laboratories and some academic institutions. Skin tests to identify reactions to allergens like pork or beef may also be used to inform AGS diagnosis. However, a positive alpha-gal sIgE test or skin test does not mean a person has AGS. Many people, particularly those who live in regions with lone star ticks, have positive alpha-gal specific IgE tests without having AGS. 

Consider the test results along with your patient’s symptoms and risk factors.

 

5. There is no treatment for AGS, but people can take prevention steps and AGS can be managed.

People can protect themselves and their family from AGS by preventing tick bites. Encourage your patients to use an Environmental Protection Agency–registered insect repellent outdoors, wear permethrin-treated clothing, and conduct thorough tick checks after outdoor activities. 

Once a person is no longer exposed to alpha-gal containing products, they should no longer experience symptoms. People with AGS should also proactively prevent tick bites. Tick bites can trigger or reactivate AGS.

For patients who have AGS, help manage their symptoms and identify alpha-gal containing products to avoid.

Dr. Kersh is Chief of the Rickettsial Zoonoses Branch, Division of Vector-Borne Diseases, Centers for Disease Control and Prevention, Atlanta, Georgia, and disclosed no relevant conflicts of interest.

CDC resources:

About Alpha-gal Syndrome | Alpha-gal Syndrome | CDC 

Clinical Testing and Diagnosis for Alpha-gal Syndrome | Alpha-gal Syndrome | CDC 

Clinical Resources | Alpha-gal Syndrome | CDC 

References 

Thompson JM et al. MMWR Morb Mortal Wkly Rep. 2023;72:815-820. 

Carpenter A et al. MMWR Morb Mortal Wkly Rep. 2023;72:809-814. Taylor ML et al. Ann Allergy, Asthma & Immunol. 2024 Jun;132(6):759.e2-764.e2. Kersh GJ et al. Ann Allergy, Asthma & Immunol. 2023 Apr;130(4):472-478.

Alpha-gal syndrome (AGS), a tickborne disease commonly called “red meat allergy,” is a serious, potentially life-threatening allergy to the carbohydrate alpha-gal. The alpha-gal carbohydrate is found in most mammals, though it is not in humans, apes, or old-world monkeys. People with AGS can have allergic reactions when they consume mammalian meat, dairy products, or other products derived from mammals. People often live with this disease for years before receiving a correct diagnosis, greatly impacting their quality of life. The number of suspected cases is also rising. 

More than 110,000 suspected AGS cases were identified between 2010 and 2022, according to a Centers for Disease Control and Prevention (CDC) report.¹ However, because the diagnosis requires a positive test and a clinical exam and some people may not get tested, as many as 450,000 people might be affected by AGS in the United States. Additionally, a CDC survey found that nearly half (42%) of US healthcare providers had never heard of AGS.² Among those who had, less than one third (29%) knew how to diagnose the condition. 

Here are 5 things clinicians need to know about AGS.

 

1. People can develop AGS after being bitten by a tick, primarily the lone star tick (Amblyomma americanum), in the United States.

In the United States, AGS is primarily associated with the bite of a lone star tick, but other kinds of ticks have not been ruled out. The majority of suspected AGS cases in the United States were reported in parts of Arkansas, Delaware, Illinois, Indiana, Kansas, Kentucky, Maryland, Mississippi, Missouri, North Carolina, Oklahoma, Tennessee, and Virginia. The lone star tick is widely distributed with established populations in Alabama, Arkansas, Connecticut, Delaware, Florida, Georgia, Illinois, Indiana, Iowa, Kansas, Kentucky, Louisiana, Michigan, Minnesota, Mississippi, Missouri, Nebraska, New Hampshire, New Jersey, New York, North Carolina, Ohio, Oklahoma, Pennsylvania, South Carolina, Tennessee, Texas, Virginia, and West Virginia. 

While AGS is associated with tick bites, more research is needed to understand the role ticks play in starting this condition, and why certain people develop AGS. Anyone can develop AGS, but most cases have been reported in adults. 

Know how to recognize the symptoms of AGS and be prepared to test, diagnose, and manage AGS, particularly in states where lone star ticks are found. 

 

2. Tick bites are only one risk factor for developing AGS. 

Many people are bitten by lone star ticks and will never develop AGS. Scientists are exploring the connection between other risk factors and developing AGS. A recent study has shown that people diagnosed with AGS may be more likely to have a family member who was also diagnosed with AGS, have another food allergy, have an allergy to stinging or biting insects, or have A or O blood types.³ 

Research has also shown that environmental risk factors could contribute to developing AGS,⁴ like living in an area with lone star ticks, remembering finding a tick on themselves, recalling multiple tick bites, living near a wooded forest, spending more time outside, or living in areas with deer, such as larger properties, wooded forests, and properties with shrubs and brush. 

Ask your patient questions about other allergies and history of recent tick bites or outdoor exposure to help determine if testing for AGS is appropriate.

 

3. Symptoms of AGS are consistently inconsistent.

There is a spectrum of how sensitive AGS patients are to alpha-gal, and reactions are often different from person to person, which can make it difficult to diagnose. The first allergic reaction to AGS typically occurs between 1-6 months after a tick bite. Symptoms commonly appear 2-6 hours after being in contact with products containing alpha-gal, like red meat (beef, pork, lamb, venison, rabbit, or other meat from mammals), dairy, and some medications. Symptoms can range from mild to severe and include hives or itchy rash; swelling of the lips, throat, tongue, or eyelids; gastrointestinal symptoms such as nausea, vomiting, or diarrhea; heartburn or indigestion; cough, shortness of breath, or difficulty breathing; dizziness or a drop in blood pressure; or anaphylaxis.

Consider AGS if a patient reports waking up in the middle of the night with allergic symptoms after eating alpha-gal containing products for dinner, if allergic reactions are delayed, or if a patient has anaphylaxis of unknown cause, adult-onset allergy, or allergic symptoms and reports a recent tick bite. 

 

4. Diagnosing AGS requires a combination of a blood test and a physical exam.

Diagnosing AGS requires a detailed patient history, physical exam, and a blood test to detect specific immunoglobulin E (IgE) antibodies specific to alpha-gal (alpha-gal sIgE). Tests for alpha-gal sIgE antibodies are available at several large commercial laboratories and some academic institutions. Skin tests to identify reactions to allergens like pork or beef may also be used to inform AGS diagnosis. However, a positive alpha-gal sIgE test or skin test does not mean a person has AGS. Many people, particularly those who live in regions with lone star ticks, have positive alpha-gal specific IgE tests without having AGS. 

Consider the test results along with your patient’s symptoms and risk factors.

 

5. There is no treatment for AGS, but people can take prevention steps and AGS can be managed.

People can protect themselves and their family from AGS by preventing tick bites. Encourage your patients to use an Environmental Protection Agency–registered insect repellent outdoors, wear permethrin-treated clothing, and conduct thorough tick checks after outdoor activities. 

Once a person is no longer exposed to alpha-gal containing products, they should no longer experience symptoms. People with AGS should also proactively prevent tick bites. Tick bites can trigger or reactivate AGS.

For patients who have AGS, help manage their symptoms and identify alpha-gal containing products to avoid.

Dr. Kersh is Chief of the Rickettsial Zoonoses Branch, Division of Vector-Borne Diseases, Centers for Disease Control and Prevention, Atlanta, Georgia, and disclosed no relevant conflicts of interest.

CDC resources:

About Alpha-gal Syndrome | Alpha-gal Syndrome | CDC 

Clinical Testing and Diagnosis for Alpha-gal Syndrome | Alpha-gal Syndrome | CDC 

Clinical Resources | Alpha-gal Syndrome | CDC 

References 

Thompson JM et al. MMWR Morb Mortal Wkly Rep. 2023;72:815-820. 

Carpenter A et al. MMWR Morb Mortal Wkly Rep. 2023;72:809-814. Taylor ML et al. Ann Allergy, Asthma & Immunol. 2024 Jun;132(6):759.e2-764.e2. Kersh GJ et al. Ann Allergy, Asthma & Immunol. 2023 Apr;130(4):472-478.

Evidence is mounting that new therapies already used to treat gut diseases, type 2 diabetes, and obesity may help people with alcohol use disorder (AUD).

Glucagon-like peptide 1 (GLP-1) receptor agonists, first used to treat diabetes and now widely used for weight loss, and fecal microbiota transplants (FMTs), used to treat diseases such as recurrent Clostridioides difficile infection, are advancing in clinical trials as potential options for treating AUD.

 

AUD Affects 28.9 Million People in the United States

In 2023, 28.9 million people aged 12 years or older in the United States had AUD (10.2% of the people in this age group). The Food and Drug Administration (FDA) has approved three medical therapies: Acamprosate, naltrexone, and disulfiram to help keep people with the disorder from returning to heavy drinking. Acamprosate’s mechanism of action is not clear, but it is thought to modulate and normalize alcohol-related changes in brain activity, thereby reducing withdrawal symptoms. Naltrexone blocks opioid receptors to reduce alcohol cravings. Disulfiram causes a toxic physical reaction when mixed with alcohol.

Some with AUD also benefit from behavioral therapies and support groups such as Alcoholics Anonymous. But for others, nothing has worked, and that’s part of the reason Lorenzo Leggio, MD, PhD, a scientist in the field of alcohol addiction with the National Institutes of Health (NIH), told this news organization that this is the “most exciting moment” for AUD treatment in his more than 2 decades of research in this area.

 

GLP-1 Agonists Showing Consistent Results

GLP-1 receptor agonists work by modulating the brain’s reward pathways, including the areas that regulate cravings and motivation.

“By dampening the reward signals associated with alcohol consumption, GLP-1 agonists may reduce cravings and heavy drinking episodes,” Fares Qeadan, PhD, MS, associate professor of biostatistics in the Department of Public Health Sciences at Loyola University Chicago in Illinois, told this news organization.

“The unique aspect of GLP-1 agonists is their ability to target both metabolic and reward systems in the brain,” he said. While naltrexone or acamprosate blocks the effects of alcohol or reduces withdrawal symptoms, “GLP-1 agonists approach addiction through a broader mechanism, potentially addressing underlying factors that contribute to cravings and compulsive behaviors,” he said.

As part of a study published in October in Addiction, Qeadan’s team found that people with AUD who were prescribed GLP-1 agonists had a 50% lower rate of severe intoxication than those who were not prescribed those medications.

“While this is observational and not yet definitive, it highlights the potential of these drugs to complement existing treatments for AUD,” he said.

Another study, a nationwide cohort study published in JAMA Psychiatry, found that using the GLP-1 receptor agonists semaglutide and liraglutide was linked to a lower risk for AUD-related hospitalizations than traditional AUD medications.

A systematic review, published last month in eClinical Medicine, concluded that, though there is little high-quality evidence demonstrating the effect of GLP-1 receptor agonists on alcohol use, “subgroup analysis from two [randomized, controlled trials] and supporting data from four observational studies suggest that GLP-1 [receptor agonists] may reduce alcohol consumption and improve outcomes in some individuals.”

Studying individual differences in response may have implications for personalized medicine, Qeadan said, as treatments could be tailored to those most likely to benefit, such as people with both metabolic dysfunction and AUD.

“These medications may offer hope for patients who struggle with addiction and have not responded to traditional therapies,” Qeadan said.

 

Exploring FMT as AUD Treatment

FMT is also a new research focus for treating AUD. Jasmohan Bajaj, MD, a gastroenterologist and liver specialist at Virginia Commonwealth University Medical Center, Richmond, is leading the Intestinal Microbiota Transplant in Alcohol-Associated Liver Disease (IMPACT) trial.

AUD has been linked with gut microbial alterations that worsen with cirrhosis. Research has shown that alcohol consumption changes the diversity of bacteria and can lead to bacterial overgrowth and progression of alcohol-associated liver disease.

FMT has been effective in rebalancing gut bacteria by transferring healthy stool from screened donors into patients who have developed an overgrowth of harmful bacteria. In the IMPACT trial, participants, who have not previously received traditional treatment for AUD or for whom treatment has not worked, are randomized either to the oral treatment capsule, which contains freeze-dried stool from a donor with healthy gut bacteria, or placebo.

The trial, sponsored by the NIH, is halfway through its target enrollment of 80.

In a previous smaller, placebo-controlled, phase 1 study, also led by Bajaj and published in Hepatology, 9 of the 10 volunteers who had severe AUD and cirrhosis experienced fewer alcohol cravings and had lower consumption after 15 days. Only three of the placebo participants saw similar improvements. Those who received the microbiota transplant also had fewer AUD-related events over 6 months.

Bajaj said that, if trials show FMT is safe and effective, he envisions the treatment as one tool in a multidisciplinary, integrated clinic that would include a hepatologist and mental health clinicians.

One benefit of the FMT treatment approach is it is given once or twice only, rather than administered regularly.

 

Current Treatments Work, But More are Needed

Leggio, who is clinical director of the National Institute on Drug Abuse Intramural Research Program, said: “We know that alcohol use disorder, and addiction in general, is a brain disease. We also know that the brain does not work in isolation. The brain is constantly interacting with the rest of the body, including with the gut.”

Leggio said it’s important to note that the three FDA-approved medications do work for alcohol addiction. He said they work as well as selective serotonin reuptake inhibitors for depression and beta-blockers for chronic heart failure.

But there are only three, and they don’t work for everyone, he noted. Those are among the reasons developing new treatments is important. New treatments could be used as an alternative or in combination with already approved treatments.

FMT is in “the very early stages” of trials testing its use for AUD, Leggio noted, adding that the studies by Bajaj’s team are among the very few addressing gut dysbiosis in AUD, and all have involved small numbers of patients. “It’s promising. It’s intriguing. It’s exciting. But we are just at the beginning.”

 

Results Consistent Across Species, Labs

GLP-1 agonists are further along in trials but still not ready for prescribing for AUD, Leggio said. The positive results have been consistent across species, different labs, and different research teams around the world.

Researchers have also explored through electronic health record emulation trials whether people already taking GLP-1 agonists for diabetes or obesity drink less alcohol compared with matched cohorts not taking GLP-1s. “They consistently show that the people who are on GLP-1s drink less,” he said.

“[Emulation trials] don’t replace the need for randomized controlled trials, Leggio noted. Leggio’s team is currently working on a randomized, placebo-controlled, double-blinded trial studying GLP-1s in relation to AUD.

 

New Directions 20-Year Highlight

This whole line of research represents “new hope” and has many implications, Leggio said. “I have been in this business for 20-plus years, and I think this is themost exciting moment when we have a very promising target in GLP-1s.”

Regardless of efficacy, he said, the focus on GLP-1 agonists and FMT for AUD has people talking more about addiction and the brain-body connection rather than assuming AUD is a result of poor choices and “bad behavior.”

The momentum of new treatments could also lead to patients and physicians having conversations about existing treatments.

“Hopefully, this momentum will help us destigmatize addiction, and by destigmatizing addiction, there will be an uptick in use of currently approved medications,” Leggio said.

Qeadan, Bajaj, and Leggio reported no relevant financial relationships.

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

Evidence is mounting that new therapies already used to treat gut diseases, type 2 diabetes, and obesity may help people with alcohol use disorder (AUD).

Glucagon-like peptide 1 (GLP-1) receptor agonists, first used to treat diabetes and now widely used for weight loss, and fecal microbiota transplants (FMTs), used to treat diseases such as recurrent Clostridioides difficile infection, are advancing in clinical trials as potential options for treating AUD.

 

AUD Affects 28.9 Million People in the United States

In 2023, 28.9 million people aged 12 years or older in the United States had AUD (10.2% of the people in this age group). The Food and Drug Administration (FDA) has approved three medical therapies: Acamprosate, naltrexone, and disulfiram to help keep people with the disorder from returning to heavy drinking. Acamprosate’s mechanism of action is not clear, but it is thought to modulate and normalize alcohol-related changes in brain activity, thereby reducing withdrawal symptoms. Naltrexone blocks opioid receptors to reduce alcohol cravings. Disulfiram causes a toxic physical reaction when mixed with alcohol.

Some with AUD also benefit from behavioral therapies and support groups such as Alcoholics Anonymous. But for others, nothing has worked, and that’s part of the reason Lorenzo Leggio, MD, PhD, a scientist in the field of alcohol addiction with the National Institutes of Health (NIH), told this news organization that this is the “most exciting moment” for AUD treatment in his more than 2 decades of research in this area.

 

GLP-1 Agonists Showing Consistent Results

GLP-1 receptor agonists work by modulating the brain’s reward pathways, including the areas that regulate cravings and motivation.

“By dampening the reward signals associated with alcohol consumption, GLP-1 agonists may reduce cravings and heavy drinking episodes,” Fares Qeadan, PhD, MS, associate professor of biostatistics in the Department of Public Health Sciences at Loyola University Chicago in Illinois, told this news organization.

“The unique aspect of GLP-1 agonists is their ability to target both metabolic and reward systems in the brain,” he said. While naltrexone or acamprosate blocks the effects of alcohol or reduces withdrawal symptoms, “GLP-1 agonists approach addiction through a broader mechanism, potentially addressing underlying factors that contribute to cravings and compulsive behaviors,” he said.

As part of a study published in October in Addiction, Qeadan’s team found that people with AUD who were prescribed GLP-1 agonists had a 50% lower rate of severe intoxication than those who were not prescribed those medications.

“While this is observational and not yet definitive, it highlights the potential of these drugs to complement existing treatments for AUD,” he said.

Another study, a nationwide cohort study published in JAMA Psychiatry, found that using the GLP-1 receptor agonists semaglutide and liraglutide was linked to a lower risk for AUD-related hospitalizations than traditional AUD medications.

A systematic review, published last month in eClinical Medicine, concluded that, though there is little high-quality evidence demonstrating the effect of GLP-1 receptor agonists on alcohol use, “subgroup analysis from two [randomized, controlled trials] and supporting data from four observational studies suggest that GLP-1 [receptor agonists] may reduce alcohol consumption and improve outcomes in some individuals.”

Studying individual differences in response may have implications for personalized medicine, Qeadan said, as treatments could be tailored to those most likely to benefit, such as people with both metabolic dysfunction and AUD.

“These medications may offer hope for patients who struggle with addiction and have not responded to traditional therapies,” Qeadan said.

 

Exploring FMT as AUD Treatment

FMT is also a new research focus for treating AUD. Jasmohan Bajaj, MD, a gastroenterologist and liver specialist at Virginia Commonwealth University Medical Center, Richmond, is leading the Intestinal Microbiota Transplant in Alcohol-Associated Liver Disease (IMPACT) trial.

AUD has been linked with gut microbial alterations that worsen with cirrhosis. Research has shown that alcohol consumption changes the diversity of bacteria and can lead to bacterial overgrowth and progression of alcohol-associated liver disease.

FMT has been effective in rebalancing gut bacteria by transferring healthy stool from screened donors into patients who have developed an overgrowth of harmful bacteria. In the IMPACT trial, participants, who have not previously received traditional treatment for AUD or for whom treatment has not worked, are randomized either to the oral treatment capsule, which contains freeze-dried stool from a donor with healthy gut bacteria, or placebo.

The trial, sponsored by the NIH, is halfway through its target enrollment of 80.

In a previous smaller, placebo-controlled, phase 1 study, also led by Bajaj and published in Hepatology, 9 of the 10 volunteers who had severe AUD and cirrhosis experienced fewer alcohol cravings and had lower consumption after 15 days. Only three of the placebo participants saw similar improvements. Those who received the microbiota transplant also had fewer AUD-related events over 6 months.

Bajaj said that, if trials show FMT is safe and effective, he envisions the treatment as one tool in a multidisciplinary, integrated clinic that would include a hepatologist and mental health clinicians.

One benefit of the FMT treatment approach is it is given once or twice only, rather than administered regularly.

 

Current Treatments Work, But More are Needed

Leggio, who is clinical director of the National Institute on Drug Abuse Intramural Research Program, said: “We know that alcohol use disorder, and addiction in general, is a brain disease. We also know that the brain does not work in isolation. The brain is constantly interacting with the rest of the body, including with the gut.”

Leggio said it’s important to note that the three FDA-approved medications do work for alcohol addiction. He said they work as well as selective serotonin reuptake inhibitors for depression and beta-blockers for chronic heart failure.

But there are only three, and they don’t work for everyone, he noted. Those are among the reasons developing new treatments is important. New treatments could be used as an alternative or in combination with already approved treatments.

FMT is in “the very early stages” of trials testing its use for AUD, Leggio noted, adding that the studies by Bajaj’s team are among the very few addressing gut dysbiosis in AUD, and all have involved small numbers of patients. “It’s promising. It’s intriguing. It’s exciting. But we are just at the beginning.”

 

Results Consistent Across Species, Labs

GLP-1 agonists are further along in trials but still not ready for prescribing for AUD, Leggio said. The positive results have been consistent across species, different labs, and different research teams around the world.

Researchers have also explored through electronic health record emulation trials whether people already taking GLP-1 agonists for diabetes or obesity drink less alcohol compared with matched cohorts not taking GLP-1s. “They consistently show that the people who are on GLP-1s drink less,” he said.

“[Emulation trials] don’t replace the need for randomized controlled trials, Leggio noted. Leggio’s team is currently working on a randomized, placebo-controlled, double-blinded trial studying GLP-1s in relation to AUD.

 

New Directions 20-Year Highlight

This whole line of research represents “new hope” and has many implications, Leggio said. “I have been in this business for 20-plus years, and I think this is themost exciting moment when we have a very promising target in GLP-1s.”

Regardless of efficacy, he said, the focus on GLP-1 agonists and FMT for AUD has people talking more about addiction and the brain-body connection rather than assuming AUD is a result of poor choices and “bad behavior.”

The momentum of new treatments could also lead to patients and physicians having conversations about existing treatments.

“Hopefully, this momentum will help us destigmatize addiction, and by destigmatizing addiction, there will be an uptick in use of currently approved medications,” Leggio said.

Qeadan, Bajaj, and Leggio reported no relevant financial relationships.

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

Evidence is mounting that new therapies already used to treat gut diseases, type 2 diabetes, and obesity may help people with alcohol use disorder (AUD).

Glucagon-like peptide 1 (GLP-1) receptor agonists, first used to treat diabetes and now widely used for weight loss, and fecal microbiota transplants (FMTs), used to treat diseases such as recurrent Clostridioides difficile infection, are advancing in clinical trials as potential options for treating AUD.

 

AUD Affects 28.9 Million People in the United States

In 2023, 28.9 million people aged 12 years or older in the United States had AUD (10.2% of the people in this age group). The Food and Drug Administration (FDA) has approved three medical therapies: Acamprosate, naltrexone, and disulfiram to help keep people with the disorder from returning to heavy drinking. Acamprosate’s mechanism of action is not clear, but it is thought to modulate and normalize alcohol-related changes in brain activity, thereby reducing withdrawal symptoms. Naltrexone blocks opioid receptors to reduce alcohol cravings. Disulfiram causes a toxic physical reaction when mixed with alcohol.

Some with AUD also benefit from behavioral therapies and support groups such as Alcoholics Anonymous. But for others, nothing has worked, and that’s part of the reason Lorenzo Leggio, MD, PhD, a scientist in the field of alcohol addiction with the National Institutes of Health (NIH), told this news organization that this is the “most exciting moment” for AUD treatment in his more than 2 decades of research in this area.

 

GLP-1 Agonists Showing Consistent Results

GLP-1 receptor agonists work by modulating the brain’s reward pathways, including the areas that regulate cravings and motivation.

“By dampening the reward signals associated with alcohol consumption, GLP-1 agonists may reduce cravings and heavy drinking episodes,” Fares Qeadan, PhD, MS, associate professor of biostatistics in the Department of Public Health Sciences at Loyola University Chicago in Illinois, told this news organization.

“The unique aspect of GLP-1 agonists is their ability to target both metabolic and reward systems in the brain,” he said. While naltrexone or acamprosate blocks the effects of alcohol or reduces withdrawal symptoms, “GLP-1 agonists approach addiction through a broader mechanism, potentially addressing underlying factors that contribute to cravings and compulsive behaviors,” he said.

As part of a study published in October in Addiction, Qeadan’s team found that people with AUD who were prescribed GLP-1 agonists had a 50% lower rate of severe intoxication than those who were not prescribed those medications.

“While this is observational and not yet definitive, it highlights the potential of these drugs to complement existing treatments for AUD,” he said.

Another study, a nationwide cohort study published in JAMA Psychiatry, found that using the GLP-1 receptor agonists semaglutide and liraglutide was linked to a lower risk for AUD-related hospitalizations than traditional AUD medications.

A systematic review, published last month in eClinical Medicine, concluded that, though there is little high-quality evidence demonstrating the effect of GLP-1 receptor agonists on alcohol use, “subgroup analysis from two [randomized, controlled trials] and supporting data from four observational studies suggest that GLP-1 [receptor agonists] may reduce alcohol consumption and improve outcomes in some individuals.”

Studying individual differences in response may have implications for personalized medicine, Qeadan said, as treatments could be tailored to those most likely to benefit, such as people with both metabolic dysfunction and AUD.

“These medications may offer hope for patients who struggle with addiction and have not responded to traditional therapies,” Qeadan said.

 

Exploring FMT as AUD Treatment

FMT is also a new research focus for treating AUD. Jasmohan Bajaj, MD, a gastroenterologist and liver specialist at Virginia Commonwealth University Medical Center, Richmond, is leading the Intestinal Microbiota Transplant in Alcohol-Associated Liver Disease (IMPACT) trial.

AUD has been linked with gut microbial alterations that worsen with cirrhosis. Research has shown that alcohol consumption changes the diversity of bacteria and can lead to bacterial overgrowth and progression of alcohol-associated liver disease.

FMT has been effective in rebalancing gut bacteria by transferring healthy stool from screened donors into patients who have developed an overgrowth of harmful bacteria. In the IMPACT trial, participants, who have not previously received traditional treatment for AUD or for whom treatment has not worked, are randomized either to the oral treatment capsule, which contains freeze-dried stool from a donor with healthy gut bacteria, or placebo.

The trial, sponsored by the NIH, is halfway through its target enrollment of 80.

In a previous smaller, placebo-controlled, phase 1 study, also led by Bajaj and published in Hepatology, 9 of the 10 volunteers who had severe AUD and cirrhosis experienced fewer alcohol cravings and had lower consumption after 15 days. Only three of the placebo participants saw similar improvements. Those who received the microbiota transplant also had fewer AUD-related events over 6 months.

Bajaj said that, if trials show FMT is safe and effective, he envisions the treatment as one tool in a multidisciplinary, integrated clinic that would include a hepatologist and mental health clinicians.

One benefit of the FMT treatment approach is it is given once or twice only, rather than administered regularly.

 

Current Treatments Work, But More are Needed

Leggio, who is clinical director of the National Institute on Drug Abuse Intramural Research Program, said: “We know that alcohol use disorder, and addiction in general, is a brain disease. We also know that the brain does not work in isolation. The brain is constantly interacting with the rest of the body, including with the gut.”

Leggio said it’s important to note that the three FDA-approved medications do work for alcohol addiction. He said they work as well as selective serotonin reuptake inhibitors for depression and beta-blockers for chronic heart failure.

But there are only three, and they don’t work for everyone, he noted. Those are among the reasons developing new treatments is important. New treatments could be used as an alternative or in combination with already approved treatments.

FMT is in “the very early stages” of trials testing its use for AUD, Leggio noted, adding that the studies by Bajaj’s team are among the very few addressing gut dysbiosis in AUD, and all have involved small numbers of patients. “It’s promising. It’s intriguing. It’s exciting. But we are just at the beginning.”

 

Results Consistent Across Species, Labs

GLP-1 agonists are further along in trials but still not ready for prescribing for AUD, Leggio said. The positive results have been consistent across species, different labs, and different research teams around the world.

Researchers have also explored through electronic health record emulation trials whether people already taking GLP-1 agonists for diabetes or obesity drink less alcohol compared with matched cohorts not taking GLP-1s. “They consistently show that the people who are on GLP-1s drink less,” he said.

“[Emulation trials] don’t replace the need for randomized controlled trials, Leggio noted. Leggio’s team is currently working on a randomized, placebo-controlled, double-blinded trial studying GLP-1s in relation to AUD.

 

New Directions 20-Year Highlight

This whole line of research represents “new hope” and has many implications, Leggio said. “I have been in this business for 20-plus years, and I think this is themost exciting moment when we have a very promising target in GLP-1s.”

Regardless of efficacy, he said, the focus on GLP-1 agonists and FMT for AUD has people talking more about addiction and the brain-body connection rather than assuming AUD is a result of poor choices and “bad behavior.”

The momentum of new treatments could also lead to patients and physicians having conversations about existing treatments.

“Hopefully, this momentum will help us destigmatize addiction, and by destigmatizing addiction, there will be an uptick in use of currently approved medications,” Leggio said.

Qeadan, Bajaj, and Leggio reported no relevant financial relationships.

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

Every year, an estimated 45 million Americans attempt some kind of diet to shed weight, especially after the holidays. Whether or not an individual is on a successful weight loss journey, at some point they probably will experience “diet fatigue.” This is the mental and emotional exhaustion associated with engaging in dieting behaviors like calorie counting, weighing and measuring food, meal planning and prepping, and restricting certain foods. 

Diet fatigue is a huge reason (but certainly not the only reason) why diets fail, as dieters can become so burned out that they ditch their diet, return to their former eating habits, blame themselves for their diet failure, and then repeat the cycle.

Alison* became my client just as her diet fatigue was starting to settle in. She had already lost 25 pounds in the prior 6 months while in a coaching program that focused primarily on hitting calorie and macro targets. She had been following an extremely high-protein regimen that relied heavily on animal sources and protein powders. I’m not against using powders to supplement protein needs, but in Alison’s case, she was consuming a powder-and-milk concoction twice per day in place of a meal with actual food. Not only had she become plain sick of the powder, but she was also concerned that all the protein was pushing vegetables off her plate. Alison had been following this plan quite strictly but admitted to indulging in weekend sweets. She recognized that this occasional indulgence could quickly morph into a full-on habit and undo her progress. While Alison had not yet reached her goal weight, we both agreed that she needed to change up her eating routine. 

Getting a patient through diet fatigue involves identifying which dieting behaviors are causing them the most angst and then guiding them toward a more sustainable approach that provides a similar benefit. For example, many dieters develop a huge disdain for calorie tracking, which they most often describe as tedious. One alternative to tracking calories is food journaling, which encourages accountability and mindfulness but is not as time-consuming as plugging every single ingredient you ingest into an app. Alison, however, didn’t have a problem with tracking, nor with weighing her food (as a Type A personality, she preferred having this kind of control). But she was clearly lacking a few things in her previous diet: variety, fiber, and flavor. In short, Alison was not enjoying her food — hence, her increased desire for treats on weekends, which she saw as a kind of reward for “being good” all week. 

To keep Alison from slipping into a weekend bingeing pattern, we discussed a few tweaks to her regimen. First, we had to ditch the protein powder in favor of balanced meals. I recommended reducing her daily protein target, which I felt was unnecessarily high. This provided some wiggle room to add a well-rounded dinner. I encouraged her to start adding spices and herbs to make dishes more exciting. 

Finally — and this one might be controversial — I encouraged Alison to actually plan for a weekly indulgence. In my experience working in the weight management space, complete restriction of a desired food always backfires, so it made sense for Alison to simply build the chocolate into her plan in a reasonable way. 

I’m confident that Alison will reach her weight loss goal (and keep the weight off) if food continues to bring her pleasure. When it comes to weight loss, I believe that if the solution is temporary, success will also be temporary. As a dietitian, preaching sustainable, long-term habit changes is my priority, not just because it’s responsible, but because it’s the only approach that truly works.

*Patient’s name changed to protect privacy. 

Ms. Hanks is a registered dietitian at Well by Messer in New York City. She disclosed no relevant conflicts of interest.

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

Every year, an estimated 45 million Americans attempt some kind of diet to shed weight, especially after the holidays. Whether or not an individual is on a successful weight loss journey, at some point they probably will experience “diet fatigue.” This is the mental and emotional exhaustion associated with engaging in dieting behaviors like calorie counting, weighing and measuring food, meal planning and prepping, and restricting certain foods. 

Diet fatigue is a huge reason (but certainly not the only reason) why diets fail, as dieters can become so burned out that they ditch their diet, return to their former eating habits, blame themselves for their diet failure, and then repeat the cycle.

Alison* became my client just as her diet fatigue was starting to settle in. She had already lost 25 pounds in the prior 6 months while in a coaching program that focused primarily on hitting calorie and macro targets. She had been following an extremely high-protein regimen that relied heavily on animal sources and protein powders. I’m not against using powders to supplement protein needs, but in Alison’s case, she was consuming a powder-and-milk concoction twice per day in place of a meal with actual food. Not only had she become plain sick of the powder, but she was also concerned that all the protein was pushing vegetables off her plate. Alison had been following this plan quite strictly but admitted to indulging in weekend sweets. She recognized that this occasional indulgence could quickly morph into a full-on habit and undo her progress. While Alison had not yet reached her goal weight, we both agreed that she needed to change up her eating routine. 

Getting a patient through diet fatigue involves identifying which dieting behaviors are causing them the most angst and then guiding them toward a more sustainable approach that provides a similar benefit. For example, many dieters develop a huge disdain for calorie tracking, which they most often describe as tedious. One alternative to tracking calories is food journaling, which encourages accountability and mindfulness but is not as time-consuming as plugging every single ingredient you ingest into an app. Alison, however, didn’t have a problem with tracking, nor with weighing her food (as a Type A personality, she preferred having this kind of control). But she was clearly lacking a few things in her previous diet: variety, fiber, and flavor. In short, Alison was not enjoying her food — hence, her increased desire for treats on weekends, which she saw as a kind of reward for “being good” all week. 

To keep Alison from slipping into a weekend bingeing pattern, we discussed a few tweaks to her regimen. First, we had to ditch the protein powder in favor of balanced meals. I recommended reducing her daily protein target, which I felt was unnecessarily high. This provided some wiggle room to add a well-rounded dinner. I encouraged her to start adding spices and herbs to make dishes more exciting. 

Finally — and this one might be controversial — I encouraged Alison to actually plan for a weekly indulgence. In my experience working in the weight management space, complete restriction of a desired food always backfires, so it made sense for Alison to simply build the chocolate into her plan in a reasonable way. 

I’m confident that Alison will reach her weight loss goal (and keep the weight off) if food continues to bring her pleasure. When it comes to weight loss, I believe that if the solution is temporary, success will also be temporary. As a dietitian, preaching sustainable, long-term habit changes is my priority, not just because it’s responsible, but because it’s the only approach that truly works.

*Patient’s name changed to protect privacy. 

Ms. Hanks is a registered dietitian at Well by Messer in New York City. She disclosed no relevant conflicts of interest.

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

Every year, an estimated 45 million Americans attempt some kind of diet to shed weight, especially after the holidays. Whether or not an individual is on a successful weight loss journey, at some point they probably will experience “diet fatigue.” This is the mental and emotional exhaustion associated with engaging in dieting behaviors like calorie counting, weighing and measuring food, meal planning and prepping, and restricting certain foods. 

Diet fatigue is a huge reason (but certainly not the only reason) why diets fail, as dieters can become so burned out that they ditch their diet, return to their former eating habits, blame themselves for their diet failure, and then repeat the cycle.

Alison* became my client just as her diet fatigue was starting to settle in. She had already lost 25 pounds in the prior 6 months while in a coaching program that focused primarily on hitting calorie and macro targets. She had been following an extremely high-protein regimen that relied heavily on animal sources and protein powders. I’m not against using powders to supplement protein needs, but in Alison’s case, she was consuming a powder-and-milk concoction twice per day in place of a meal with actual food. Not only had she become plain sick of the powder, but she was also concerned that all the protein was pushing vegetables off her plate. Alison had been following this plan quite strictly but admitted to indulging in weekend sweets. She recognized that this occasional indulgence could quickly morph into a full-on habit and undo her progress. While Alison had not yet reached her goal weight, we both agreed that she needed to change up her eating routine. 

Getting a patient through diet fatigue involves identifying which dieting behaviors are causing them the most angst and then guiding them toward a more sustainable approach that provides a similar benefit. For example, many dieters develop a huge disdain for calorie tracking, which they most often describe as tedious. One alternative to tracking calories is food journaling, which encourages accountability and mindfulness but is not as time-consuming as plugging every single ingredient you ingest into an app. Alison, however, didn’t have a problem with tracking, nor with weighing her food (as a Type A personality, she preferred having this kind of control). But she was clearly lacking a few things in her previous diet: variety, fiber, and flavor. In short, Alison was not enjoying her food — hence, her increased desire for treats on weekends, which she saw as a kind of reward for “being good” all week. 

To keep Alison from slipping into a weekend bingeing pattern, we discussed a few tweaks to her regimen. First, we had to ditch the protein powder in favor of balanced meals. I recommended reducing her daily protein target, which I felt was unnecessarily high. This provided some wiggle room to add a well-rounded dinner. I encouraged her to start adding spices and herbs to make dishes more exciting. 

Finally — and this one might be controversial — I encouraged Alison to actually plan for a weekly indulgence. In my experience working in the weight management space, complete restriction of a desired food always backfires, so it made sense for Alison to simply build the chocolate into her plan in a reasonable way. 

I’m confident that Alison will reach her weight loss goal (and keep the weight off) if food continues to bring her pleasure. When it comes to weight loss, I believe that if the solution is temporary, success will also be temporary. As a dietitian, preaching sustainable, long-term habit changes is my priority, not just because it’s responsible, but because it’s the only approach that truly works.

*Patient’s name changed to protect privacy. 

Ms. Hanks is a registered dietitian at Well by Messer in New York City. She disclosed no relevant conflicts of interest.

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

For people with obesity or type 2 diabetes, glucagon-like peptide 1 (GLP-1) agonists (including Mounjaro, Wegovy, and Ozempic) have been labeled miracle drugs. But they aren’t miraculous for everyone. Research indicates a significant portion of people discontinue using them within a year.

The main problems with GLP-1 agonists are that they are expensive and have a fairly high rate of side effects — such as nausea, vomiting, diarrhea, or constipation. Another big one is muscle loss.

A new study, published in Nature, shows a potential alternative to GLP-1 agonists with fewer side effects, at least in mice and nonhuman primates.

This lack of side effects, particularly in how the potential drug causes no muscle loss — and in fact engages muscle for some of its effect — sets it apart and makes it a potential alternative to GLP-1s. The key is not just reducing appetite but also increasing energy expenditure.

 

How It Works

The new approach targets a protein called NK2R — a member of the neurokinin receptor family, which has a role in a variety of physiological processes, including pain sensation, anxiety, and inflammation. 

“We were looking to see genetic linkages to metabolic health, and there NK2R was,” said Zach Gerhart-Hines, PhD, a professor studying molecular metabolism at the University of Copenhagen in Denmark and principal investigator of the study. The group then created a few long-acting agonists that are selective for NK2R. So far, they’ve tested them in mice and nonhuman primates.

“The data on new medicines targeting NK2R is very promising and highlights the potential of both reducing food intake and increasing energy expenditure,” said Daniel Drucker, MD, an endocrinologist and researcher at Lunenfeld-Tanenbaum Research Institute in Toronto who was not involved in the study.

“The drug activates a certain region in the hindbrain of the animal, which is controlling food intake, and it does so by reducing appetite without increasing nausea or vomiting,” explained Frederike Sass, a research assistant at the University of Copenhagen in Copenhagen, Denmark, who led the study.

Gerhart-Hines said that even at the highest dose, there were no incidents of vomiting among the nonhuman primates. Mice can’t vomit, but there are ways to tell if they feel unwell from a drug. One way researchers test that is to start feeding the mice sweetened water at the same time they’re given a drug. Then later, when the mice are no longer on the drug, they’re given a choice between sweetened and unsweetened water. If they weren’t feeling well on the drug, they’ll choose plain water because they associate the sweet water with feeling bad, otherwise mice prefer sweet water. Sass said that with the NK2R agonist, they continued to drink sweet water after the treatment, whereas when they gave the mice semaglutide, the mice preferred plain water posttreatment.

The researchers also monitored the animals’ psychological health, as NK2R has been associated with anxiety, but they observed no behavioral changes.

 

The Key Mechanism at Work

One big question is how the NK2R agonists work. The amphetamines people used for weight loss during the 1950s and 1960s worked by making people more active. GLP-1 agonists reduce appetite and lower blood sugar. This is not that. In their studies with animals, the researchers didn’t observe that the animals were more active nor were there changes in other biomarkers like insulin. So far, the main difference they found with the NK2R agonists is an increase in thermogenesis in certain muscles.

Another benefit of the NK2R treatments is that they don’t seem to have a big impact on lean mass — the nonfat component of body weight, namely muscle, bones, and organs. Studies indicate that 25%-39% of weight loss on GLP-1 agonists is lost muscle. According to DEXA scans of the mice, Gerhart-Hines said they observed no lean mass loss. (In mice, he noted, GLP-1 agonists can cause up to 50% lean mass loss).

And for people with both diabetes and obesity, “what we found with NK2R is that obese and diabetic models, whether mice or monkeys, respond much better to that treatment in terms of glucose control and body weight loss,” Gerhart-Hines said. He explained that GLP-1 agonists don’t work quite as well for weight loss in people with diabetes because the drug stimulates insulin production in a system that already has insulin issues and can cause more sugar to be stored as fat.

Further, GLP-1 agonists are peptide drugs, which are expensive to make. The NK2R agonists are small molecules that would be cheaper to produce, Gerhart-Hines believes. One candidate they’re testing would likely be given once daily, another once weekly.

The current surge in obesity and diabetes may be a direct consequence of our bodies’ decreased energy expenditure. “Compared to 80s and 90s, the average person is more physically active, but the overarching basal resting energy expenditure has gone down,” said Gerhart-Hines, according to research by John Speakman at the University of Aberdeen, Scotland. We don’t know why, though, he said, but guesses it could be our diets or climate controlled environments.

But the NK2R agonists are among the many currently being studied for weight loss, and it may be hard to compete with the GLP-1 agonists. “As GLP-1 medicines will soon achieve 25% weight loss and have an extensively studied safety profile, the task of producing better drugs that work well in most people, are well tolerated and also reduce the complications of cardiometabolic disease, is challenging but not impossible,” said Drucker.

Gerhart-Hines said they plan to start trials in humans in the next year, but he suspects it will be another 6 or 7 years before it comes to market, if the trials are successful.

“There’s people who want [a GLP-1 agonist] and can’t even get it,” Gerhart-Hines said. As far as weight loss drugs, he noted, “we are not even saturating the market right now.”

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

For people with obesity or type 2 diabetes, glucagon-like peptide 1 (GLP-1) agonists (including Mounjaro, Wegovy, and Ozempic) have been labeled miracle drugs. But they aren’t miraculous for everyone. Research indicates a significant portion of people discontinue using them within a year.

The main problems with GLP-1 agonists are that they are expensive and have a fairly high rate of side effects — such as nausea, vomiting, diarrhea, or constipation. Another big one is muscle loss.

A new study, published in Nature, shows a potential alternative to GLP-1 agonists with fewer side effects, at least in mice and nonhuman primates.

This lack of side effects, particularly in how the potential drug causes no muscle loss — and in fact engages muscle for some of its effect — sets it apart and makes it a potential alternative to GLP-1s. The key is not just reducing appetite but also increasing energy expenditure.

 

How It Works

The new approach targets a protein called NK2R — a member of the neurokinin receptor family, which has a role in a variety of physiological processes, including pain sensation, anxiety, and inflammation. 

“We were looking to see genetic linkages to metabolic health, and there NK2R was,” said Zach Gerhart-Hines, PhD, a professor studying molecular metabolism at the University of Copenhagen in Denmark and principal investigator of the study. The group then created a few long-acting agonists that are selective for NK2R. So far, they’ve tested them in mice and nonhuman primates.

“The data on new medicines targeting NK2R is very promising and highlights the potential of both reducing food intake and increasing energy expenditure,” said Daniel Drucker, MD, an endocrinologist and researcher at Lunenfeld-Tanenbaum Research Institute in Toronto who was not involved in the study.

“The drug activates a certain region in the hindbrain of the animal, which is controlling food intake, and it does so by reducing appetite without increasing nausea or vomiting,” explained Frederike Sass, a research assistant at the University of Copenhagen in Copenhagen, Denmark, who led the study.

Gerhart-Hines said that even at the highest dose, there were no incidents of vomiting among the nonhuman primates. Mice can’t vomit, but there are ways to tell if they feel unwell from a drug. One way researchers test that is to start feeding the mice sweetened water at the same time they’re given a drug. Then later, when the mice are no longer on the drug, they’re given a choice between sweetened and unsweetened water. If they weren’t feeling well on the drug, they’ll choose plain water because they associate the sweet water with feeling bad, otherwise mice prefer sweet water. Sass said that with the NK2R agonist, they continued to drink sweet water after the treatment, whereas when they gave the mice semaglutide, the mice preferred plain water posttreatment.

The researchers also monitored the animals’ psychological health, as NK2R has been associated with anxiety, but they observed no behavioral changes.

 

The Key Mechanism at Work

One big question is how the NK2R agonists work. The amphetamines people used for weight loss during the 1950s and 1960s worked by making people more active. GLP-1 agonists reduce appetite and lower blood sugar. This is not that. In their studies with animals, the researchers didn’t observe that the animals were more active nor were there changes in other biomarkers like insulin. So far, the main difference they found with the NK2R agonists is an increase in thermogenesis in certain muscles.

Another benefit of the NK2R treatments is that they don’t seem to have a big impact on lean mass — the nonfat component of body weight, namely muscle, bones, and organs. Studies indicate that 25%-39% of weight loss on GLP-1 agonists is lost muscle. According to DEXA scans of the mice, Gerhart-Hines said they observed no lean mass loss. (In mice, he noted, GLP-1 agonists can cause up to 50% lean mass loss).

And for people with both diabetes and obesity, “what we found with NK2R is that obese and diabetic models, whether mice or monkeys, respond much better to that treatment in terms of glucose control and body weight loss,” Gerhart-Hines said. He explained that GLP-1 agonists don’t work quite as well for weight loss in people with diabetes because the drug stimulates insulin production in a system that already has insulin issues and can cause more sugar to be stored as fat.

Further, GLP-1 agonists are peptide drugs, which are expensive to make. The NK2R agonists are small molecules that would be cheaper to produce, Gerhart-Hines believes. One candidate they’re testing would likely be given once daily, another once weekly.

The current surge in obesity and diabetes may be a direct consequence of our bodies’ decreased energy expenditure. “Compared to 80s and 90s, the average person is more physically active, but the overarching basal resting energy expenditure has gone down,” said Gerhart-Hines, according to research by John Speakman at the University of Aberdeen, Scotland. We don’t know why, though, he said, but guesses it could be our diets or climate controlled environments.

But the NK2R agonists are among the many currently being studied for weight loss, and it may be hard to compete with the GLP-1 agonists. “As GLP-1 medicines will soon achieve 25% weight loss and have an extensively studied safety profile, the task of producing better drugs that work well in most people, are well tolerated and also reduce the complications of cardiometabolic disease, is challenging but not impossible,” said Drucker.

Gerhart-Hines said they plan to start trials in humans in the next year, but he suspects it will be another 6 or 7 years before it comes to market, if the trials are successful.

“There’s people who want [a GLP-1 agonist] and can’t even get it,” Gerhart-Hines said. As far as weight loss drugs, he noted, “we are not even saturating the market right now.”

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

For people with obesity or type 2 diabetes, glucagon-like peptide 1 (GLP-1) agonists (including Mounjaro, Wegovy, and Ozempic) have been labeled miracle drugs. But they aren’t miraculous for everyone. Research indicates a significant portion of people discontinue using them within a year.

The main problems with GLP-1 agonists are that they are expensive and have a fairly high rate of side effects — such as nausea, vomiting, diarrhea, or constipation. Another big one is muscle loss.

A new study, published in Nature, shows a potential alternative to GLP-1 agonists with fewer side effects, at least in mice and nonhuman primates.

This lack of side effects, particularly in how the potential drug causes no muscle loss — and in fact engages muscle for some of its effect — sets it apart and makes it a potential alternative to GLP-1s. The key is not just reducing appetite but also increasing energy expenditure.

 

How It Works

The new approach targets a protein called NK2R — a member of the neurokinin receptor family, which has a role in a variety of physiological processes, including pain sensation, anxiety, and inflammation. 

“We were looking to see genetic linkages to metabolic health, and there NK2R was,” said Zach Gerhart-Hines, PhD, a professor studying molecular metabolism at the University of Copenhagen in Denmark and principal investigator of the study. The group then created a few long-acting agonists that are selective for NK2R. So far, they’ve tested them in mice and nonhuman primates.

“The data on new medicines targeting NK2R is very promising and highlights the potential of both reducing food intake and increasing energy expenditure,” said Daniel Drucker, MD, an endocrinologist and researcher at Lunenfeld-Tanenbaum Research Institute in Toronto who was not involved in the study.

“The drug activates a certain region in the hindbrain of the animal, which is controlling food intake, and it does so by reducing appetite without increasing nausea or vomiting,” explained Frederike Sass, a research assistant at the University of Copenhagen in Copenhagen, Denmark, who led the study.

Gerhart-Hines said that even at the highest dose, there were no incidents of vomiting among the nonhuman primates. Mice can’t vomit, but there are ways to tell if they feel unwell from a drug. One way researchers test that is to start feeding the mice sweetened water at the same time they’re given a drug. Then later, when the mice are no longer on the drug, they’re given a choice between sweetened and unsweetened water. If they weren’t feeling well on the drug, they’ll choose plain water because they associate the sweet water with feeling bad, otherwise mice prefer sweet water. Sass said that with the NK2R agonist, they continued to drink sweet water after the treatment, whereas when they gave the mice semaglutide, the mice preferred plain water posttreatment.

The researchers also monitored the animals’ psychological health, as NK2R has been associated with anxiety, but they observed no behavioral changes.

 

The Key Mechanism at Work

One big question is how the NK2R agonists work. The amphetamines people used for weight loss during the 1950s and 1960s worked by making people more active. GLP-1 agonists reduce appetite and lower blood sugar. This is not that. In their studies with animals, the researchers didn’t observe that the animals were more active nor were there changes in other biomarkers like insulin. So far, the main difference they found with the NK2R agonists is an increase in thermogenesis in certain muscles.

Another benefit of the NK2R treatments is that they don’t seem to have a big impact on lean mass — the nonfat component of body weight, namely muscle, bones, and organs. Studies indicate that 25%-39% of weight loss on GLP-1 agonists is lost muscle. According to DEXA scans of the mice, Gerhart-Hines said they observed no lean mass loss. (In mice, he noted, GLP-1 agonists can cause up to 50% lean mass loss).

And for people with both diabetes and obesity, “what we found with NK2R is that obese and diabetic models, whether mice or monkeys, respond much better to that treatment in terms of glucose control and body weight loss,” Gerhart-Hines said. He explained that GLP-1 agonists don’t work quite as well for weight loss in people with diabetes because the drug stimulates insulin production in a system that already has insulin issues and can cause more sugar to be stored as fat.

Further, GLP-1 agonists are peptide drugs, which are expensive to make. The NK2R agonists are small molecules that would be cheaper to produce, Gerhart-Hines believes. One candidate they’re testing would likely be given once daily, another once weekly.

The current surge in obesity and diabetes may be a direct consequence of our bodies’ decreased energy expenditure. “Compared to 80s and 90s, the average person is more physically active, but the overarching basal resting energy expenditure has gone down,” said Gerhart-Hines, according to research by John Speakman at the University of Aberdeen, Scotland. We don’t know why, though, he said, but guesses it could be our diets or climate controlled environments.

But the NK2R agonists are among the many currently being studied for weight loss, and it may be hard to compete with the GLP-1 agonists. “As GLP-1 medicines will soon achieve 25% weight loss and have an extensively studied safety profile, the task of producing better drugs that work well in most people, are well tolerated and also reduce the complications of cardiometabolic disease, is challenging but not impossible,” said Drucker.

Gerhart-Hines said they plan to start trials in humans in the next year, but he suspects it will be another 6 or 7 years before it comes to market, if the trials are successful.

“There’s people who want [a GLP-1 agonist] and can’t even get it,” Gerhart-Hines said. As far as weight loss drugs, he noted, “we are not even saturating the market right now.”

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