Doug Brunk

NEW ORLEANS — Although not cost-saving, bariatric surgery appears to be a good value for the money, the results from a large single-center study showed.

“The long-term cost-effectiveness of bariatric surgery will largely depend on the natural history and extent of late postsurgical complications and costs,” Dr. William H. Herman said at the annual scientific sessions of the American Diabetes Association.

To gain a better understanding of the cost-effectiveness of bariatric surgery in a managed care population, Dr. Herman and his associates studied 221 patients who underwent Roux-en-Y procedures in a Southeastern Michigan HMO between May 1, 2001, and June 30, 2005. Patients were asked to complete the EQ-5D, a standardized tool used to measure health-related quality of life before, and 1 year after, bariatric surgery.

The patients' mean age was 42 years, 88% were female, and the mean body mass index before surgery was 52 kg/m

Nearly two-thirds of the patients (64%) had open surgical procedures. The remainder had laparoscopic procedures.

One year after surgery, the mean BMI fell from 51 kg/m

Overall, patients dropped from a mean weight of 320 pounds to a mean of 192 pounds, a loss of nearly 130 pounds in each person. The average BMI fell from 52 kg/m

For example, 98% reported improvements in hypertension, 100% reported improvements in diabetes, and 92% reported improvements in obstructive sleep apnea.

Total per-member costs were about $600 per month in the 6 months prior to surgery, dropped to about $400 per month in the 12 months after surgery, then rose to about $600 per month 1 year after surgery.

“In the 6 months before bariatric surgery, there was some ramp-up in outpatient pharmacy costs and, not unexpectedly, an increase in clinic costs and diagnostic and laboratory testing likely related to the preoperative period,” Dr. Herman said.

“Following bariatric surgery there was a dramatic reduction in outpatient pharmacy costs but some increase in inpatient costs, which seemed to increase the year following surgery,” he added.

The surgery itself cost about $12,000, with a slightly lower cost for the laparoscopic procedure.

When the researchers prospectively assessed presurgical quality of life, they found that the average health utility scores improved by 0.14 1 year after surgery.

In analyses that took a lifetime time horizon, adopted a payer perspective, and discounted costs and health utilities at 3% per year, the cost-utility ratio for bariatric surgery was about $15,000 per quality-adjusted life year gained.

Dr. Herman also reported that bariatric surgery was more cost effective in older patients, more obese patients, and nondiabetic patients, and when performed laparoscopically.

Dr. Herman disclosed that he serves as an adviser to Johnson & Johnson and Sanofi-Aventis, and as a consultant to Amylin Pharmaceuticals Inc.

After surgery we saw 'a dramatic reduction in outpatient pharmacy costs but some increase in inpatient costs.'

Source DR. HERMAN

NEW ORLEANS — Although not cost-saving, bariatric surgery appears to be a good value for the money, the results from a large single-center study showed.

“The long-term cost-effectiveness of bariatric surgery will largely depend on the natural history and extent of late postsurgical complications and costs,” Dr. William H. Herman said at the annual scientific sessions of the American Diabetes Association.

To gain a better understanding of the cost-effectiveness of bariatric surgery in a managed care population, Dr. Herman and his associates studied 221 patients who underwent Roux-en-Y procedures in a Southeastern Michigan HMO between May 1, 2001, and June 30, 2005. Patients were asked to complete the EQ-5D, a standardized tool used to measure health-related quality of life before, and 1 year after, bariatric surgery.

The patients' mean age was 42 years, 88% were female, and the mean body mass index before surgery was 52 kg/m

Nearly two-thirds of the patients (64%) had open surgical procedures. The remainder had laparoscopic procedures.

One year after surgery, the mean BMI fell from 51 kg/m

Overall, patients dropped from a mean weight of 320 pounds to a mean of 192 pounds, a loss of nearly 130 pounds in each person. The average BMI fell from 52 kg/m

For example, 98% reported improvements in hypertension, 100% reported improvements in diabetes, and 92% reported improvements in obstructive sleep apnea.

Total per-member costs were about $600 per month in the 6 months prior to surgery, dropped to about $400 per month in the 12 months after surgery, then rose to about $600 per month 1 year after surgery.

“In the 6 months before bariatric surgery, there was some ramp-up in outpatient pharmacy costs and, not unexpectedly, an increase in clinic costs and diagnostic and laboratory testing likely related to the preoperative period,” Dr. Herman said.

“Following bariatric surgery there was a dramatic reduction in outpatient pharmacy costs but some increase in inpatient costs, which seemed to increase the year following surgery,” he added.

The surgery itself cost about $12,000, with a slightly lower cost for the laparoscopic procedure.

When the researchers prospectively assessed presurgical quality of life, they found that the average health utility scores improved by 0.14 1 year after surgery.

In analyses that took a lifetime time horizon, adopted a payer perspective, and discounted costs and health utilities at 3% per year, the cost-utility ratio for bariatric surgery was about $15,000 per quality-adjusted life year gained.

Dr. Herman also reported that bariatric surgery was more cost effective in older patients, more obese patients, and nondiabetic patients, and when performed laparoscopically.

Dr. Herman disclosed that he serves as an adviser to Johnson & Johnson and Sanofi-Aventis, and as a consultant to Amylin Pharmaceuticals Inc.

After surgery we saw 'a dramatic reduction in outpatient pharmacy costs but some increase in inpatient costs.'

Source DR. HERMAN

NEW ORLEANS — Although not cost-saving, bariatric surgery appears to be a good value for the money, the results from a large single-center study showed.

“The long-term cost-effectiveness of bariatric surgery will largely depend on the natural history and extent of late postsurgical complications and costs,” Dr. William H. Herman said at the annual scientific sessions of the American Diabetes Association.

To gain a better understanding of the cost-effectiveness of bariatric surgery in a managed care population, Dr. Herman and his associates studied 221 patients who underwent Roux-en-Y procedures in a Southeastern Michigan HMO between May 1, 2001, and June 30, 2005. Patients were asked to complete the EQ-5D, a standardized tool used to measure health-related quality of life before, and 1 year after, bariatric surgery.

The patients' mean age was 42 years, 88% were female, and the mean body mass index before surgery was 52 kg/m

Nearly two-thirds of the patients (64%) had open surgical procedures. The remainder had laparoscopic procedures.

One year after surgery, the mean BMI fell from 51 kg/m

Overall, patients dropped from a mean weight of 320 pounds to a mean of 192 pounds, a loss of nearly 130 pounds in each person. The average BMI fell from 52 kg/m

For example, 98% reported improvements in hypertension, 100% reported improvements in diabetes, and 92% reported improvements in obstructive sleep apnea.

Total per-member costs were about $600 per month in the 6 months prior to surgery, dropped to about $400 per month in the 12 months after surgery, then rose to about $600 per month 1 year after surgery.

“In the 6 months before bariatric surgery, there was some ramp-up in outpatient pharmacy costs and, not unexpectedly, an increase in clinic costs and diagnostic and laboratory testing likely related to the preoperative period,” Dr. Herman said.

“Following bariatric surgery there was a dramatic reduction in outpatient pharmacy costs but some increase in inpatient costs, which seemed to increase the year following surgery,” he added.

The surgery itself cost about $12,000, with a slightly lower cost for the laparoscopic procedure.

When the researchers prospectively assessed presurgical quality of life, they found that the average health utility scores improved by 0.14 1 year after surgery.

In analyses that took a lifetime time horizon, adopted a payer perspective, and discounted costs and health utilities at 3% per year, the cost-utility ratio for bariatric surgery was about $15,000 per quality-adjusted life year gained.

Dr. Herman also reported that bariatric surgery was more cost effective in older patients, more obese patients, and nondiabetic patients, and when performed laparoscopically.

Dr. Herman disclosed that he serves as an adviser to Johnson & Johnson and Sanofi-Aventis, and as a consultant to Amylin Pharmaceuticals Inc.

After surgery we saw 'a dramatic reduction in outpatient pharmacy costs but some increase in inpatient costs.'

Source DR. HERMAN

NEW ORLEANS — The rate of obesity appears to be increasing more quickly among young adults with type 1 diabetes compared with national prevalence data, results from a 5-year, single-center study showed.

At the same time, obesity significantly increased the likelihood of having elevated systolic and diastolic blood pressures and LDL cholesterol levels, and reduced HDL cholesterol levels, after adjusting for demographic factors, Samuel L. Ellis, Pharm.D., reported at the annual scientific sessions of the American Diabetes Association. “We need to continue this research and look at the impact of obesity on progression and complications,” he said.

While obesity is closely related to metabolic syndrome and type 2 diabetes in older adults, little is known about the prevalence and associated clinical effects of obesity in patients with type 1 diabetes. “There are limited data outside of the clinical trial population such as those in the Diabetes Control and Complications Trial,” said Dr. Ellis of the department of clinical pharmacy at the University of Colorado Denver School of Pharmacy, Aurora.

He and his associates evaluated the electronic medical records of all patients with type 1 diabetes aged 18–50 years who received care at the Barbara Davis Center for Childhood Diabetes in Aurora during 2000–2005. Patients were excluded if they were pregnant during the study period or if they had type 2 diabetes.

The number of patients seen per year ranged from 1,141 in 2000 to 1,573 in 2005. The mean age of patients at baseline was 23 years and their mean hemoglobin A_1c level was 8.5%.

Patients were followed for the primary outcome of progression to obesity, defined as a body mass index of 30 kg/m

Secondary outcomes studied included the effects of obesity on blood pressure, lipids, and HbA_1c levels.

Dr. Ellis reported that the number of patients with a body mass index of 30 kg/m

Patients in the overweight and obese groups had significantly greater LDL levels during the study period compared with patients who had a BMI of less than 25 kg/m

In addition, patients in the overweight and obese groups had significantly reduced HDL concentrations at all time periods compared with those in the healthy BMI group. “We also noticed that those individuals who were obese had significantly lower HDLs in 2003, 2004, and 2005,” Dr. Ellis said.

A similar pattern was seen from a systolic BP standpoint. Patients in the healthy BMI group had fairly normal systolic blood pressures, “but patients in the obese group had elevated systolic blood pressures throughout the time period,” he said. “There were significant differences between the obese and the healthy BMI groups as well as between the obese and overweight groups.”

At the same time, diastolic blood pressures in the obese group were 5–10 mm Hg higher than those in the healthy BMI group, and 2–4 mm Hg higher than those in the overweight group.

Mean HbA_1c values throughout the study period were significantly lower in the obese group compared with patients in the healthy BMI group (8.41% vs. 8.06%, respectively). This finding may be the result of aggressive insulin therapy to lower HbA_1c, which in turn results in weight gain, Dr. Ellis said in an interview. “But usually we don't see this degree of weight change with a decrease in HbA_1c,” he said.

Dr. Ellis said that the study's observational, single-center design makes it difficult “to create an external validity that we can take outside of the state of Colorado.”

Dr. Ellis disclosed that he has served as a paid consultant for Merck.

NEW ORLEANS — The rate of obesity appears to be increasing more quickly among young adults with type 1 diabetes compared with national prevalence data, results from a 5-year, single-center study showed.

At the same time, obesity significantly increased the likelihood of having elevated systolic and diastolic blood pressures and LDL cholesterol levels, and reduced HDL cholesterol levels, after adjusting for demographic factors, Samuel L. Ellis, Pharm.D., reported at the annual scientific sessions of the American Diabetes Association. “We need to continue this research and look at the impact of obesity on progression and complications,” he said.

While obesity is closely related to metabolic syndrome and type 2 diabetes in older adults, little is known about the prevalence and associated clinical effects of obesity in patients with type 1 diabetes. “There are limited data outside of the clinical trial population such as those in the Diabetes Control and Complications Trial,” said Dr. Ellis of the department of clinical pharmacy at the University of Colorado Denver School of Pharmacy, Aurora.

He and his associates evaluated the electronic medical records of all patients with type 1 diabetes aged 18–50 years who received care at the Barbara Davis Center for Childhood Diabetes in Aurora during 2000–2005. Patients were excluded if they were pregnant during the study period or if they had type 2 diabetes.

The number of patients seen per year ranged from 1,141 in 2000 to 1,573 in 2005. The mean age of patients at baseline was 23 years and their mean hemoglobin A_1c level was 8.5%.

Patients were followed for the primary outcome of progression to obesity, defined as a body mass index of 30 kg/m

Secondary outcomes studied included the effects of obesity on blood pressure, lipids, and HbA_1c levels.

Dr. Ellis reported that the number of patients with a body mass index of 30 kg/m

Patients in the overweight and obese groups had significantly greater LDL levels during the study period compared with patients who had a BMI of less than 25 kg/m

In addition, patients in the overweight and obese groups had significantly reduced HDL concentrations at all time periods compared with those in the healthy BMI group. “We also noticed that those individuals who were obese had significantly lower HDLs in 2003, 2004, and 2005,” Dr. Ellis said.

A similar pattern was seen from a systolic BP standpoint. Patients in the healthy BMI group had fairly normal systolic blood pressures, “but patients in the obese group had elevated systolic blood pressures throughout the time period,” he said. “There were significant differences between the obese and the healthy BMI groups as well as between the obese and overweight groups.”

At the same time, diastolic blood pressures in the obese group were 5–10 mm Hg higher than those in the healthy BMI group, and 2–4 mm Hg higher than those in the overweight group.

Mean HbA_1c values throughout the study period were significantly lower in the obese group compared with patients in the healthy BMI group (8.41% vs. 8.06%, respectively). This finding may be the result of aggressive insulin therapy to lower HbA_1c, which in turn results in weight gain, Dr. Ellis said in an interview. “But usually we don't see this degree of weight change with a decrease in HbA_1c,” he said.

Dr. Ellis said that the study's observational, single-center design makes it difficult “to create an external validity that we can take outside of the state of Colorado.”

Dr. Ellis disclosed that he has served as a paid consultant for Merck.

NEW ORLEANS — The rate of obesity appears to be increasing more quickly among young adults with type 1 diabetes compared with national prevalence data, results from a 5-year, single-center study showed.

At the same time, obesity significantly increased the likelihood of having elevated systolic and diastolic blood pressures and LDL cholesterol levels, and reduced HDL cholesterol levels, after adjusting for demographic factors, Samuel L. Ellis, Pharm.D., reported at the annual scientific sessions of the American Diabetes Association. “We need to continue this research and look at the impact of obesity on progression and complications,” he said.

While obesity is closely related to metabolic syndrome and type 2 diabetes in older adults, little is known about the prevalence and associated clinical effects of obesity in patients with type 1 diabetes. “There are limited data outside of the clinical trial population such as those in the Diabetes Control and Complications Trial,” said Dr. Ellis of the department of clinical pharmacy at the University of Colorado Denver School of Pharmacy, Aurora.

He and his associates evaluated the electronic medical records of all patients with type 1 diabetes aged 18–50 years who received care at the Barbara Davis Center for Childhood Diabetes in Aurora during 2000–2005. Patients were excluded if they were pregnant during the study period or if they had type 2 diabetes.

The number of patients seen per year ranged from 1,141 in 2000 to 1,573 in 2005. The mean age of patients at baseline was 23 years and their mean hemoglobin A_1c level was 8.5%.

Patients were followed for the primary outcome of progression to obesity, defined as a body mass index of 30 kg/m

Secondary outcomes studied included the effects of obesity on blood pressure, lipids, and HbA_1c levels.

Dr. Ellis reported that the number of patients with a body mass index of 30 kg/m

Patients in the overweight and obese groups had significantly greater LDL levels during the study period compared with patients who had a BMI of less than 25 kg/m

In addition, patients in the overweight and obese groups had significantly reduced HDL concentrations at all time periods compared with those in the healthy BMI group. “We also noticed that those individuals who were obese had significantly lower HDLs in 2003, 2004, and 2005,” Dr. Ellis said.

A similar pattern was seen from a systolic BP standpoint. Patients in the healthy BMI group had fairly normal systolic blood pressures, “but patients in the obese group had elevated systolic blood pressures throughout the time period,” he said. “There were significant differences between the obese and the healthy BMI groups as well as between the obese and overweight groups.”

At the same time, diastolic blood pressures in the obese group were 5–10 mm Hg higher than those in the healthy BMI group, and 2–4 mm Hg higher than those in the overweight group.

Mean HbA_1c values throughout the study period were significantly lower in the obese group compared with patients in the healthy BMI group (8.41% vs. 8.06%, respectively). This finding may be the result of aggressive insulin therapy to lower HbA_1c, which in turn results in weight gain, Dr. Ellis said in an interview. “But usually we don't see this degree of weight change with a decrease in HbA_1c,” he said.

Dr. Ellis said that the study's observational, single-center design makes it difficult “to create an external validity that we can take outside of the state of Colorado.”

Dr. Ellis disclosed that he has served as a paid consultant for Merck.

NEW ORLEANS — Although not cost-saving, bariatric surgery appears to be a good value for the money, results from a large single-center study showed.

“The long-term cost-effectiveness of bariatric surgery will largely depend on the natural history and extent of late postsurgical complications and costs,” Dr. William H. Herman said at the annual scientific sessions of the American Diabetes Association.

To better understand the cost-effectiveness of bariatric surgery in a managed care population, Dr. Herman and his associates studied 221 patients who underwent Roux-en-Y procedures in a Southeastern Michigan HMO in May 2001-June 2005. Patients completed the EQ-5D, a tool used to measure health-related quality of life before and after bariatric surgery.

The patients' mean age was 42 years, 88% were female, and body mass index before surgery was 52 kg/m

Nearly two-thirds (64%) had open surgical procedures. The remainder had laparoscopic procedures. One year after surgery, the mean BMI fell from 51 to 31 in women and from 59 to 35 in men. Overall, patients dropped from a mean weight of 320 pounds to a mean of 192 pounds, a loss of nearly 130 pounds in each person. The average BMI fell from 52 to 31, excess weight fell from 191 pounds to 64 pounds, and patients reported that their comorbidities were improved. For example, 98% reported improvements in hypertension, 100% reported improvements in diabetes, and 92% reported improvements in OSA.

Total per-member costs were about $600 per month in the 6 months prior to surgery, dropped to about $400 per month in the 12 months after surgery, then rose to about $600 per month after 1 year post surgery.

“In the 6 months before bariatric surgery, there was some ramp-up in outpatient pharmacy costs and, not unexpectedly, an increase in clinic costs and diagnostic and laboratory testing likely related to the preoperative period,” Dr. Herman said. “Following bariatric surgery there was a dramatic reduction in outpatient pharmacy costs but some increase in inpatient costs, which seemed to increase the year following surgery.”

When the researchers prospectively assessed presurgical quality of life, they found that the average health utility scores improved by 0.14 1 year after surgery.

In analyses that took a lifetime time horizon, adopted a payer perspective, and discounted costs and health utilities at 3% per year, the cost-utility ratio for bariatric surgery was about $15,000 per quality-adjusted life-year gained, said Dr. Herman, who is an adviser to Johnson & Johnson and Sanofi-Aventis, and a consultant to Amylin Pharmaceuticals Inc.

After surgery we saw 'a dramatic reduction in outpatient pharmacy costs but some increase in inpatient costs.' DR. HERMAN

NEW ORLEANS — Although not cost-saving, bariatric surgery appears to be a good value for the money, results from a large single-center study showed.

“The long-term cost-effectiveness of bariatric surgery will largely depend on the natural history and extent of late postsurgical complications and costs,” Dr. William H. Herman said at the annual scientific sessions of the American Diabetes Association.

To better understand the cost-effectiveness of bariatric surgery in a managed care population, Dr. Herman and his associates studied 221 patients who underwent Roux-en-Y procedures in a Southeastern Michigan HMO in May 2001-June 2005. Patients completed the EQ-5D, a tool used to measure health-related quality of life before and after bariatric surgery.

The patients' mean age was 42 years, 88% were female, and body mass index before surgery was 52 kg/m

Nearly two-thirds (64%) had open surgical procedures. The remainder had laparoscopic procedures. One year after surgery, the mean BMI fell from 51 to 31 in women and from 59 to 35 in men. Overall, patients dropped from a mean weight of 320 pounds to a mean of 192 pounds, a loss of nearly 130 pounds in each person. The average BMI fell from 52 to 31, excess weight fell from 191 pounds to 64 pounds, and patients reported that their comorbidities were improved. For example, 98% reported improvements in hypertension, 100% reported improvements in diabetes, and 92% reported improvements in OSA.

Total per-member costs were about $600 per month in the 6 months prior to surgery, dropped to about $400 per month in the 12 months after surgery, then rose to about $600 per month after 1 year post surgery.

“In the 6 months before bariatric surgery, there was some ramp-up in outpatient pharmacy costs and, not unexpectedly, an increase in clinic costs and diagnostic and laboratory testing likely related to the preoperative period,” Dr. Herman said. “Following bariatric surgery there was a dramatic reduction in outpatient pharmacy costs but some increase in inpatient costs, which seemed to increase the year following surgery.”

When the researchers prospectively assessed presurgical quality of life, they found that the average health utility scores improved by 0.14 1 year after surgery.

In analyses that took a lifetime time horizon, adopted a payer perspective, and discounted costs and health utilities at 3% per year, the cost-utility ratio for bariatric surgery was about $15,000 per quality-adjusted life-year gained, said Dr. Herman, who is an adviser to Johnson & Johnson and Sanofi-Aventis, and a consultant to Amylin Pharmaceuticals Inc.

After surgery we saw 'a dramatic reduction in outpatient pharmacy costs but some increase in inpatient costs.' DR. HERMAN

NEW ORLEANS — Although not cost-saving, bariatric surgery appears to be a good value for the money, results from a large single-center study showed.

“The long-term cost-effectiveness of bariatric surgery will largely depend on the natural history and extent of late postsurgical complications and costs,” Dr. William H. Herman said at the annual scientific sessions of the American Diabetes Association.

To better understand the cost-effectiveness of bariatric surgery in a managed care population, Dr. Herman and his associates studied 221 patients who underwent Roux-en-Y procedures in a Southeastern Michigan HMO in May 2001-June 2005. Patients completed the EQ-5D, a tool used to measure health-related quality of life before and after bariatric surgery.

The patients' mean age was 42 years, 88% were female, and body mass index before surgery was 52 kg/m

Nearly two-thirds (64%) had open surgical procedures. The remainder had laparoscopic procedures. One year after surgery, the mean BMI fell from 51 to 31 in women and from 59 to 35 in men. Overall, patients dropped from a mean weight of 320 pounds to a mean of 192 pounds, a loss of nearly 130 pounds in each person. The average BMI fell from 52 to 31, excess weight fell from 191 pounds to 64 pounds, and patients reported that their comorbidities were improved. For example, 98% reported improvements in hypertension, 100% reported improvements in diabetes, and 92% reported improvements in OSA.

Total per-member costs were about $600 per month in the 6 months prior to surgery, dropped to about $400 per month in the 12 months after surgery, then rose to about $600 per month after 1 year post surgery.

“In the 6 months before bariatric surgery, there was some ramp-up in outpatient pharmacy costs and, not unexpectedly, an increase in clinic costs and diagnostic and laboratory testing likely related to the preoperative period,” Dr. Herman said. “Following bariatric surgery there was a dramatic reduction in outpatient pharmacy costs but some increase in inpatient costs, which seemed to increase the year following surgery.”

When the researchers prospectively assessed presurgical quality of life, they found that the average health utility scores improved by 0.14 1 year after surgery.

In analyses that took a lifetime time horizon, adopted a payer perspective, and discounted costs and health utilities at 3% per year, the cost-utility ratio for bariatric surgery was about $15,000 per quality-adjusted life-year gained, said Dr. Herman, who is an adviser to Johnson & Johnson and Sanofi-Aventis, and a consultant to Amylin Pharmaceuticals Inc.

After surgery we saw 'a dramatic reduction in outpatient pharmacy costs but some increase in inpatient costs.' DR. HERMAN

NEW ORLEANS — An investigational oral agent that combines naltrexone and bupropion produced clinically meaningful weight loss at 56 weeks, results from a multicenter phase III trial showed.

Bupropion is a norepinephrine-dopamine reuptake inhibitor that is approved for the treatment of depression and smoking cessation, while naltrexone is an opioid antagonist that is approved for alcohol and opioid dependence.

The investigational agent, known as Contrave (Orexigen Therapeutics Inc., San Diego), combines the two drugs and targets hunger, fullness, and reward centers in the brain that control the balance of food intake and energy expenditure, Thomas A. Wadden, Ph.D., said at the annual scientific sessions of the American Diabetes Association.

Pending results from three additional phase III clinical trials expected to be announced in late 2009, Orexigen is on track to submit a New Drug Application to the Food and Drug Administration in the first half of 2010.

Dr. Wadden, a psychologist who directs the Center for Weight and Eating Disorders at the University of Pennsylvania, Philadelphia, and his coinvestigators enrolled 793 patients with a body mass index between 27 kg/m

Of the 793 patients, 591 were randomized to the study drug, which consisted of 32 mg of naltrexone and 360 mg bupropion per day, while 202 were randomized to placebo. The coprimary end points were percentage change in body weight and the proportion of patients who achieved a 5% loss of weight.

The mean age of patients was 46 years, 90% were female, 70% were white, and their mean BMI was 37 kg/m

Overall, 460 patients (58%) completed the study. At 56 weeks, a modified intent-to-treat analysis showed that patients in the treatment group lost 9.3% of their body weight, compared with a loss of 5.1% in the placebo patients, a statistically significant difference.

In addition, significantly more patients in the treatment group than in the placebo group achieved a weight loss of 5% or more (66% vs. 42%, respectively). A similar pattern was seen for those who achieved a weight loss of 10% or more (42% vs. 20%) and for those who achieved a weight loss of 15% or more (29% vs. 11%).

The overall discontinuation rate due to adverse events was 26% in the treatment group, compared with 13% in the placebo group. The most frequent adverse events were nausea (34% in the treatment group vs. 11% in the placebo group), headache (24% vs. 18%), and constipation (24% vs. 14%).

“Nausea had a fairly rapid onset in participants, was generally mild or moderate, and tended to resolve in the first 4 weeks, and in most patients by 12 weeks,” noted Dr. Wadden, professor of psychology in psychiatry at the University of Pennsylvania. “But there were some isolated cases that went further out.”

The most frequent psychiatric adverse events reported were insomnia (9% in the treatment group vs. 6% in the placebo group), anxiety (5% vs. 4%), sleep disorder (2% vs. 3%), and depressed mood (2% vs. 4%).

Two serious cases of cholecystitis occurred in the treatment group and were believed to be triggered by rapid and significant loss of body weight.

Dr. Wadden disclosed that he is adviser to Orexigen Therapeutics Inc., which funded the study, as well as to Merck & Co., Novo Nordisk Inc., and Vivus Inc.

Patients in the treatment group lost 9.3% of their body weight, compared with a 5.1% loss in the placebo group. DR. WADDEN

NEW ORLEANS — An investigational oral agent that combines naltrexone and bupropion produced clinically meaningful weight loss at 56 weeks, results from a multicenter phase III trial showed.

Bupropion is a norepinephrine-dopamine reuptake inhibitor that is approved for the treatment of depression and smoking cessation, while naltrexone is an opioid antagonist that is approved for alcohol and opioid dependence.

The investigational agent, known as Contrave (Orexigen Therapeutics Inc., San Diego), combines the two drugs and targets hunger, fullness, and reward centers in the brain that control the balance of food intake and energy expenditure, Thomas A. Wadden, Ph.D., said at the annual scientific sessions of the American Diabetes Association.

Pending results from three additional phase III clinical trials expected to be announced in late 2009, Orexigen is on track to submit a New Drug Application to the Food and Drug Administration in the first half of 2010.

Dr. Wadden, a psychologist who directs the Center for Weight and Eating Disorders at the University of Pennsylvania, Philadelphia, and his coinvestigators enrolled 793 patients with a body mass index between 27 kg/m

Of the 793 patients, 591 were randomized to the study drug, which consisted of 32 mg of naltrexone and 360 mg bupropion per day, while 202 were randomized to placebo. The coprimary end points were percentage change in body weight and the proportion of patients who achieved a 5% loss of weight.

The mean age of patients was 46 years, 90% were female, 70% were white, and their mean BMI was 37 kg/m

Overall, 460 patients (58%) completed the study. At 56 weeks, a modified intent-to-treat analysis showed that patients in the treatment group lost 9.3% of their body weight, compared with a loss of 5.1% in the placebo patients, a statistically significant difference.

In addition, significantly more patients in the treatment group than in the placebo group achieved a weight loss of 5% or more (66% vs. 42%, respectively). A similar pattern was seen for those who achieved a weight loss of 10% or more (42% vs. 20%) and for those who achieved a weight loss of 15% or more (29% vs. 11%).

The overall discontinuation rate due to adverse events was 26% in the treatment group, compared with 13% in the placebo group. The most frequent adverse events were nausea (34% in the treatment group vs. 11% in the placebo group), headache (24% vs. 18%), and constipation (24% vs. 14%).

“Nausea had a fairly rapid onset in participants, was generally mild or moderate, and tended to resolve in the first 4 weeks, and in most patients by 12 weeks,” noted Dr. Wadden, professor of psychology in psychiatry at the University of Pennsylvania. “But there were some isolated cases that went further out.”

The most frequent psychiatric adverse events reported were insomnia (9% in the treatment group vs. 6% in the placebo group), anxiety (5% vs. 4%), sleep disorder (2% vs. 3%), and depressed mood (2% vs. 4%).

Two serious cases of cholecystitis occurred in the treatment group and were believed to be triggered by rapid and significant loss of body weight.

Dr. Wadden disclosed that he is adviser to Orexigen Therapeutics Inc., which funded the study, as well as to Merck & Co., Novo Nordisk Inc., and Vivus Inc.

Patients in the treatment group lost 9.3% of their body weight, compared with a 5.1% loss in the placebo group. DR. WADDEN

NEW ORLEANS — An investigational oral agent that combines naltrexone and bupropion produced clinically meaningful weight loss at 56 weeks, results from a multicenter phase III trial showed.

Bupropion is a norepinephrine-dopamine reuptake inhibitor that is approved for the treatment of depression and smoking cessation, while naltrexone is an opioid antagonist that is approved for alcohol and opioid dependence.

The investigational agent, known as Contrave (Orexigen Therapeutics Inc., San Diego), combines the two drugs and targets hunger, fullness, and reward centers in the brain that control the balance of food intake and energy expenditure, Thomas A. Wadden, Ph.D., said at the annual scientific sessions of the American Diabetes Association.

Pending results from three additional phase III clinical trials expected to be announced in late 2009, Orexigen is on track to submit a New Drug Application to the Food and Drug Administration in the first half of 2010.

Dr. Wadden, a psychologist who directs the Center for Weight and Eating Disorders at the University of Pennsylvania, Philadelphia, and his coinvestigators enrolled 793 patients with a body mass index between 27 kg/m

Of the 793 patients, 591 were randomized to the study drug, which consisted of 32 mg of naltrexone and 360 mg bupropion per day, while 202 were randomized to placebo. The coprimary end points were percentage change in body weight and the proportion of patients who achieved a 5% loss of weight.

The mean age of patients was 46 years, 90% were female, 70% were white, and their mean BMI was 37 kg/m

Overall, 460 patients (58%) completed the study. At 56 weeks, a modified intent-to-treat analysis showed that patients in the treatment group lost 9.3% of their body weight, compared with a loss of 5.1% in the placebo patients, a statistically significant difference.

In addition, significantly more patients in the treatment group than in the placebo group achieved a weight loss of 5% or more (66% vs. 42%, respectively). A similar pattern was seen for those who achieved a weight loss of 10% or more (42% vs. 20%) and for those who achieved a weight loss of 15% or more (29% vs. 11%).

The overall discontinuation rate due to adverse events was 26% in the treatment group, compared with 13% in the placebo group. The most frequent adverse events were nausea (34% in the treatment group vs. 11% in the placebo group), headache (24% vs. 18%), and constipation (24% vs. 14%).

“Nausea had a fairly rapid onset in participants, was generally mild or moderate, and tended to resolve in the first 4 weeks, and in most patients by 12 weeks,” noted Dr. Wadden, professor of psychology in psychiatry at the University of Pennsylvania. “But there were some isolated cases that went further out.”

The most frequent psychiatric adverse events reported were insomnia (9% in the treatment group vs. 6% in the placebo group), anxiety (5% vs. 4%), sleep disorder (2% vs. 3%), and depressed mood (2% vs. 4%).

Two serious cases of cholecystitis occurred in the treatment group and were believed to be triggered by rapid and significant loss of body weight.

Dr. Wadden disclosed that he is adviser to Orexigen Therapeutics Inc., which funded the study, as well as to Merck & Co., Novo Nordisk Inc., and Vivus Inc.

Patients in the treatment group lost 9.3% of their body weight, compared with a 5.1% loss in the placebo group. DR. WADDEN

SAN DIEGO — About one-third of patients referred to an asthma specialty clinic who were believed to have difficult to control asthma actually had vocal cord dysfunction, results from a single-center study showed.

“If patients have been many different medicines—they've been on oral or inhaled steroids and they're not responding— it's worth checking to see if they actually have asthma or not,” study coauthor Catherine Vitari, R.N., said in an interview during a poster session at an international conference of the American Thoracic Society.

In a study led by her associate, Dr. Sally E. Wenzel, a pulmonologist and the director of the Asthma Institute at the University of Pittsburgh Medical Center, the researchers reviewed the charts of 152 new patients evaluated at the institute between December 2006 and September 2008 in an effort to verify if the diagnosis of severe asthma was substantiated or not.

Of the 152 patients 119 (78%) had a presenting diagnosis of asthma while 33 had another diagnosis such as dyspnea, cough, and emphysema. All patients underwent a full evaluation.

Ms. Vitari, a clinical research nurse at the Asthma Institute, reported that 40 of the 119 patients who presented with an asthma diagnosis underwent methacholine challenges with laryngoscopy because their history and physical suggested asthma may not be the primary diagnosis. Of these 40 patients, 39 had a negative test, which precluded the diagnosis of asthma in 33% of the 119 patients. “We didn't expect to see this,” she commented. “That's a pretty high percentage of people referred for asthma who didn't actually have asthma.”

She also noted that four of seven patients who presented with a diagnosis of cough, which may indicate asthma, had methacholine challenges with laryngoscopy that showed vocal cord dysfunction; the three other patients were diagnosed with vocal cord dysfunction based on their exam and testing.

Ms. Vitari noted that it's Dr. Wenzel's practice to perform a laryngoscopy at the time of the methacholine challenge “to see if the vocal cords are closing or spasming, indicating vocal cord dysfunction, or if it's truly asthma,” she explained. “If you think it's vocal cord dysfunction and you send the patient to ENT instead to do a laryngoscopy and they don't see anything, it could be that the vocal cord dysfunction isn't acting up at that time since the spasms can be episodic and/or related to triggering events/stimuli.”

She acknowledged certain limitations of the study including its single center design and the fact that only one physician did the assessments. The researchers had no conflicts to disclose.

Thirty-three percent of people referred for asthma didn't actually have asthma. DR. WENZEL

SAN DIEGO — About one-third of patients referred to an asthma specialty clinic who were believed to have difficult to control asthma actually had vocal cord dysfunction, results from a single-center study showed.

“If patients have been many different medicines—they've been on oral or inhaled steroids and they're not responding— it's worth checking to see if they actually have asthma or not,” study coauthor Catherine Vitari, R.N., said in an interview during a poster session at an international conference of the American Thoracic Society.

In a study led by her associate, Dr. Sally E. Wenzel, a pulmonologist and the director of the Asthma Institute at the University of Pittsburgh Medical Center, the researchers reviewed the charts of 152 new patients evaluated at the institute between December 2006 and September 2008 in an effort to verify if the diagnosis of severe asthma was substantiated or not.

Of the 152 patients 119 (78%) had a presenting diagnosis of asthma while 33 had another diagnosis such as dyspnea, cough, and emphysema. All patients underwent a full evaluation.

Ms. Vitari, a clinical research nurse at the Asthma Institute, reported that 40 of the 119 patients who presented with an asthma diagnosis underwent methacholine challenges with laryngoscopy because their history and physical suggested asthma may not be the primary diagnosis. Of these 40 patients, 39 had a negative test, which precluded the diagnosis of asthma in 33% of the 119 patients. “We didn't expect to see this,” she commented. “That's a pretty high percentage of people referred for asthma who didn't actually have asthma.”

She also noted that four of seven patients who presented with a diagnosis of cough, which may indicate asthma, had methacholine challenges with laryngoscopy that showed vocal cord dysfunction; the three other patients were diagnosed with vocal cord dysfunction based on their exam and testing.

Ms. Vitari noted that it's Dr. Wenzel's practice to perform a laryngoscopy at the time of the methacholine challenge “to see if the vocal cords are closing or spasming, indicating vocal cord dysfunction, or if it's truly asthma,” she explained. “If you think it's vocal cord dysfunction and you send the patient to ENT instead to do a laryngoscopy and they don't see anything, it could be that the vocal cord dysfunction isn't acting up at that time since the spasms can be episodic and/or related to triggering events/stimuli.”

She acknowledged certain limitations of the study including its single center design and the fact that only one physician did the assessments. The researchers had no conflicts to disclose.

Thirty-three percent of people referred for asthma didn't actually have asthma. DR. WENZEL

SAN DIEGO — About one-third of patients referred to an asthma specialty clinic who were believed to have difficult to control asthma actually had vocal cord dysfunction, results from a single-center study showed.

“If patients have been many different medicines—they've been on oral or inhaled steroids and they're not responding— it's worth checking to see if they actually have asthma or not,” study coauthor Catherine Vitari, R.N., said in an interview during a poster session at an international conference of the American Thoracic Society.

In a study led by her associate, Dr. Sally E. Wenzel, a pulmonologist and the director of the Asthma Institute at the University of Pittsburgh Medical Center, the researchers reviewed the charts of 152 new patients evaluated at the institute between December 2006 and September 2008 in an effort to verify if the diagnosis of severe asthma was substantiated or not.

Of the 152 patients 119 (78%) had a presenting diagnosis of asthma while 33 had another diagnosis such as dyspnea, cough, and emphysema. All patients underwent a full evaluation.

Ms. Vitari, a clinical research nurse at the Asthma Institute, reported that 40 of the 119 patients who presented with an asthma diagnosis underwent methacholine challenges with laryngoscopy because their history and physical suggested asthma may not be the primary diagnosis. Of these 40 patients, 39 had a negative test, which precluded the diagnosis of asthma in 33% of the 119 patients. “We didn't expect to see this,” she commented. “That's a pretty high percentage of people referred for asthma who didn't actually have asthma.”

She also noted that four of seven patients who presented with a diagnosis of cough, which may indicate asthma, had methacholine challenges with laryngoscopy that showed vocal cord dysfunction; the three other patients were diagnosed with vocal cord dysfunction based on their exam and testing.

Ms. Vitari noted that it's Dr. Wenzel's practice to perform a laryngoscopy at the time of the methacholine challenge “to see if the vocal cords are closing or spasming, indicating vocal cord dysfunction, or if it's truly asthma,” she explained. “If you think it's vocal cord dysfunction and you send the patient to ENT instead to do a laryngoscopy and they don't see anything, it could be that the vocal cord dysfunction isn't acting up at that time since the spasms can be episodic and/or related to triggering events/stimuli.”

She acknowledged certain limitations of the study including its single center design and the fact that only one physician did the assessments. The researchers had no conflicts to disclose.

Thirty-three percent of people referred for asthma didn't actually have asthma. DR. WENZEL

SAN DIEGO — Results of two phase III studies of pirfenidone, an oral antifibrotic and anti-inflammatory agent, have shown that the drug could slow the deterioration of lung capacity in patients with idiopathic pulmonary fibrosis.

The 72-week-long trials, known as CAPACITY 1 and CAPACITY 2, enrolled 779 patients at 110 sites in 11 countries.

“The findings of the CAPACITY trials, coupled with the results of the phase II and phase III studies in Japan and the urgent unmet medical need, suggest that pirfenidone may provide a meaningful clinical benefit in patients with IPF,” trial cochair Paul Noble said during an international conference of the American Thoracic Society.

Manufactured by InterMune Inc., pirfenidone is currently approved in Japan for the treatment of IPF. InterMune expects to submit a New Drug Application for the agent to the Food and Drug Administration in the summer of 2009.

Patients were eligible for the studies if they had a diagnosis of pulmonary fibrosis confirmed by CT scan or by biopsy and if they had a forced vital capacity (FVC) that was 50% of predicted value or greater and a diffusing capacity of the lung for carbon monoxide that was 35% of predicted value or greater.

The 344 patients in CAPACITY 1 were randomized to receive pirfenidone 2,403 mg/day or placebo for 72 weeks, while the 435 patients in CAPACITY 2 were randomized to receive either pirfenidone 2,403 mg/day, pirfenidone 1,197 mg/day, or placebo for 72 weeks. The primary end point was change in percent predicted FVC from baseline to week 72.

The mean age of patients in CAPACITY 1 was 68 years, while the mean age of CAPACITY 2 patients was 67 years, said Dr. Noble, professor of medicine and chief of pulmonary, allergy, and critical care medicine at Duke University, Durham, N.C.

In CAPACITY 2, patients in the treatment group achieved a significant reduction in change in percent predicted FVC at week 72, compared with placebo (−6.49% vs. −9.55%, respectively), and an increase in progression-free survival time (hazard ratio of 0.64). The treatment group also demonstrated a favorable effect on change in FVC category (P = .001).

In CAPACITY 1, there was no significant mean change in percent predicted FVC at week 72 between the treatment and placebo groups (−6.49% vs. −7.23%, respectively), but there was evidence of a treatment benefit at each assessment through week 48. “CAPACITY 1 did not achieve statistical significance on the primary end point,” Dr. Noble said. “However, results were generally consistent with and supportive of CAPACITY 2.”

According to a prepared statement from InterMune, a pooled analysis of categorical FVC change from the two studies “showed that 30% fewer patients experienced a 10% or greater decrease in FVC at week 72 in the pirfenidone group than in the placebo group. This magnitude of decline is considered clinically meaningful, as a 10% decline in percent predicted FVC has been shown in multiple studies to be an independent predictor of mortality in patients with IPF. In addition, 40% more patients in the pirfenidone group did not experience a decline in percent predicted FVC at week 72 versus baseline compared to those who received placebo.”

At the meeting, Dr. Noble reported that the pattern of adverse events in both trials was generally comparable to those observed in previous clinical studies of pirfenidone. The most common adverse events in the pirfenidone group compared with placebo were nausea (35% vs. 18% in CAPACITY 2, and 38% vs. 16% in CAPACITY 1), rash (31% vs. 10%, and 34% vs. 13%), fatigue (28% vs. 21%, and 33% vs. 20%), diarrhea (25% vs. 17%, and 33% vs. 21%), dyspepsia (17% vs. 9%, and 21% vs. 6%), and dizziness (19% vs. 10%, and 18% vs. 10%).

Rash was generally mild to moderate in both studies; only two patients (one in each CAPACITY study) who received pirfenidone had a severe rash.

Researchers also analyzed the incidence of patients who died during the treatment period, which was defined as the time between receiving the first dose of treatment and 28 days after receiving the last dose. In CAPACITY 1, 5% of the pirfenidone group died during the treatment period, compared with 9% of the placebo group. In CAPACITY 2, 6% of pirfenidone patients died during the treatment period, compared with 8% of placebo patients.

“CAPACITY 2 demonstrated a statistically significant and a clinically meaningful effect on the primary end point of change in percent predicted FVC and the secondary end points of progression-free survival and categorical change in percent predicted FVC,” Dr. Noble concluded. “CAPACITY 1 did not, and it failed to achieve statistical significance on the primary end point.”

The studies were funded by InterMune. Dr. Noble disclosed that he has served as a consultant, steering committee member, or cochair of a steering committee for InterMune, Actelion Pharmaceuticals Ltd., Boehringer Ingelheim GmbH, and Novartis.

SAN DIEGO — Results of two phase III studies of pirfenidone, an oral antifibrotic and anti-inflammatory agent, have shown that the drug could slow the deterioration of lung capacity in patients with idiopathic pulmonary fibrosis.

The 72-week-long trials, known as CAPACITY 1 and CAPACITY 2, enrolled 779 patients at 110 sites in 11 countries.

“The findings of the CAPACITY trials, coupled with the results of the phase II and phase III studies in Japan and the urgent unmet medical need, suggest that pirfenidone may provide a meaningful clinical benefit in patients with IPF,” trial cochair Paul Noble said during an international conference of the American Thoracic Society.

Manufactured by InterMune Inc., pirfenidone is currently approved in Japan for the treatment of IPF. InterMune expects to submit a New Drug Application for the agent to the Food and Drug Administration in the summer of 2009.

Patients were eligible for the studies if they had a diagnosis of pulmonary fibrosis confirmed by CT scan or by biopsy and if they had a forced vital capacity (FVC) that was 50% of predicted value or greater and a diffusing capacity of the lung for carbon monoxide that was 35% of predicted value or greater.

The 344 patients in CAPACITY 1 were randomized to receive pirfenidone 2,403 mg/day or placebo for 72 weeks, while the 435 patients in CAPACITY 2 were randomized to receive either pirfenidone 2,403 mg/day, pirfenidone 1,197 mg/day, or placebo for 72 weeks. The primary end point was change in percent predicted FVC from baseline to week 72.

The mean age of patients in CAPACITY 1 was 68 years, while the mean age of CAPACITY 2 patients was 67 years, said Dr. Noble, professor of medicine and chief of pulmonary, allergy, and critical care medicine at Duke University, Durham, N.C.

In CAPACITY 2, patients in the treatment group achieved a significant reduction in change in percent predicted FVC at week 72, compared with placebo (−6.49% vs. −9.55%, respectively), and an increase in progression-free survival time (hazard ratio of 0.64). The treatment group also demonstrated a favorable effect on change in FVC category (P = .001).

In CAPACITY 1, there was no significant mean change in percent predicted FVC at week 72 between the treatment and placebo groups (−6.49% vs. −7.23%, respectively), but there was evidence of a treatment benefit at each assessment through week 48. “CAPACITY 1 did not achieve statistical significance on the primary end point,” Dr. Noble said. “However, results were generally consistent with and supportive of CAPACITY 2.”

According to a prepared statement from InterMune, a pooled analysis of categorical FVC change from the two studies “showed that 30% fewer patients experienced a 10% or greater decrease in FVC at week 72 in the pirfenidone group than in the placebo group. This magnitude of decline is considered clinically meaningful, as a 10% decline in percent predicted FVC has been shown in multiple studies to be an independent predictor of mortality in patients with IPF. In addition, 40% more patients in the pirfenidone group did not experience a decline in percent predicted FVC at week 72 versus baseline compared to those who received placebo.”

At the meeting, Dr. Noble reported that the pattern of adverse events in both trials was generally comparable to those observed in previous clinical studies of pirfenidone. The most common adverse events in the pirfenidone group compared with placebo were nausea (35% vs. 18% in CAPACITY 2, and 38% vs. 16% in CAPACITY 1), rash (31% vs. 10%, and 34% vs. 13%), fatigue (28% vs. 21%, and 33% vs. 20%), diarrhea (25% vs. 17%, and 33% vs. 21%), dyspepsia (17% vs. 9%, and 21% vs. 6%), and dizziness (19% vs. 10%, and 18% vs. 10%).

Rash was generally mild to moderate in both studies; only two patients (one in each CAPACITY study) who received pirfenidone had a severe rash.

Researchers also analyzed the incidence of patients who died during the treatment period, which was defined as the time between receiving the first dose of treatment and 28 days after receiving the last dose. In CAPACITY 1, 5% of the pirfenidone group died during the treatment period, compared with 9% of the placebo group. In CAPACITY 2, 6% of pirfenidone patients died during the treatment period, compared with 8% of placebo patients.

“CAPACITY 2 demonstrated a statistically significant and a clinically meaningful effect on the primary end point of change in percent predicted FVC and the secondary end points of progression-free survival and categorical change in percent predicted FVC,” Dr. Noble concluded. “CAPACITY 1 did not, and it failed to achieve statistical significance on the primary end point.”

The studies were funded by InterMune. Dr. Noble disclosed that he has served as a consultant, steering committee member, or cochair of a steering committee for InterMune, Actelion Pharmaceuticals Ltd., Boehringer Ingelheim GmbH, and Novartis.

SAN DIEGO — Results of two phase III studies of pirfenidone, an oral antifibrotic and anti-inflammatory agent, have shown that the drug could slow the deterioration of lung capacity in patients with idiopathic pulmonary fibrosis.

The 72-week-long trials, known as CAPACITY 1 and CAPACITY 2, enrolled 779 patients at 110 sites in 11 countries.

“The findings of the CAPACITY trials, coupled with the results of the phase II and phase III studies in Japan and the urgent unmet medical need, suggest that pirfenidone may provide a meaningful clinical benefit in patients with IPF,” trial cochair Paul Noble said during an international conference of the American Thoracic Society.

Manufactured by InterMune Inc., pirfenidone is currently approved in Japan for the treatment of IPF. InterMune expects to submit a New Drug Application for the agent to the Food and Drug Administration in the summer of 2009.

Patients were eligible for the studies if they had a diagnosis of pulmonary fibrosis confirmed by CT scan or by biopsy and if they had a forced vital capacity (FVC) that was 50% of predicted value or greater and a diffusing capacity of the lung for carbon monoxide that was 35% of predicted value or greater.

The 344 patients in CAPACITY 1 were randomized to receive pirfenidone 2,403 mg/day or placebo for 72 weeks, while the 435 patients in CAPACITY 2 were randomized to receive either pirfenidone 2,403 mg/day, pirfenidone 1,197 mg/day, or placebo for 72 weeks. The primary end point was change in percent predicted FVC from baseline to week 72.

The mean age of patients in CAPACITY 1 was 68 years, while the mean age of CAPACITY 2 patients was 67 years, said Dr. Noble, professor of medicine and chief of pulmonary, allergy, and critical care medicine at Duke University, Durham, N.C.

In CAPACITY 2, patients in the treatment group achieved a significant reduction in change in percent predicted FVC at week 72, compared with placebo (−6.49% vs. −9.55%, respectively), and an increase in progression-free survival time (hazard ratio of 0.64). The treatment group also demonstrated a favorable effect on change in FVC category (P = .001).

In CAPACITY 1, there was no significant mean change in percent predicted FVC at week 72 between the treatment and placebo groups (−6.49% vs. −7.23%, respectively), but there was evidence of a treatment benefit at each assessment through week 48. “CAPACITY 1 did not achieve statistical significance on the primary end point,” Dr. Noble said. “However, results were generally consistent with and supportive of CAPACITY 2.”

According to a prepared statement from InterMune, a pooled analysis of categorical FVC change from the two studies “showed that 30% fewer patients experienced a 10% or greater decrease in FVC at week 72 in the pirfenidone group than in the placebo group. This magnitude of decline is considered clinically meaningful, as a 10% decline in percent predicted FVC has been shown in multiple studies to be an independent predictor of mortality in patients with IPF. In addition, 40% more patients in the pirfenidone group did not experience a decline in percent predicted FVC at week 72 versus baseline compared to those who received placebo.”

At the meeting, Dr. Noble reported that the pattern of adverse events in both trials was generally comparable to those observed in previous clinical studies of pirfenidone. The most common adverse events in the pirfenidone group compared with placebo were nausea (35% vs. 18% in CAPACITY 2, and 38% vs. 16% in CAPACITY 1), rash (31% vs. 10%, and 34% vs. 13%), fatigue (28% vs. 21%, and 33% vs. 20%), diarrhea (25% vs. 17%, and 33% vs. 21%), dyspepsia (17% vs. 9%, and 21% vs. 6%), and dizziness (19% vs. 10%, and 18% vs. 10%).

Rash was generally mild to moderate in both studies; only two patients (one in each CAPACITY study) who received pirfenidone had a severe rash.

Researchers also analyzed the incidence of patients who died during the treatment period, which was defined as the time between receiving the first dose of treatment and 28 days after receiving the last dose. In CAPACITY 1, 5% of the pirfenidone group died during the treatment period, compared with 9% of the placebo group. In CAPACITY 2, 6% of pirfenidone patients died during the treatment period, compared with 8% of placebo patients.

“CAPACITY 2 demonstrated a statistically significant and a clinically meaningful effect on the primary end point of change in percent predicted FVC and the secondary end points of progression-free survival and categorical change in percent predicted FVC,” Dr. Noble concluded. “CAPACITY 1 did not, and it failed to achieve statistical significance on the primary end point.”

The studies were funded by InterMune. Dr. Noble disclosed that he has served as a consultant, steering committee member, or cochair of a steering committee for InterMune, Actelion Pharmaceuticals Ltd., Boehringer Ingelheim GmbH, and Novartis.

The rate of cervical human papillomavirus infection among women with systemic lupus erythematosus increased from 12% to 25% after 3 years, judging from results from a novel study presented at the annual European Congress of Rheumatology.

Moreover, patients were twice as likely to acquire high-risk HPV infection than low-risk HPV infection.

“Information about the natural history of HPV infection in SLE is lacking,” lead investigator Dr. Lai-Shan Tam said in an interview. “Whether immunosuppression related to SLE itself and/or the use of immunosuppressants would result in an increased incidence and risk of persistent HPV infection has never been studied.”

Dr. Tam and her associates evaluated 144 women with SLE at 6-month intervals for up to 3 years. During each visit, a Pap test, a test for HPV DNA, and a clinical assessment were performed in an effort to ascertain the incidence, clearance, and persistence of HPV infection. The mean age of the patients was 41 years, and mean disease duration was 8.6 years. The total duration of follow-up was 4,006 patient-months.

The cumulative prevalence of HPV infection increased from 12% at baseline to 25% after 3 years, and 19% of patients experienced a total of 69 incident infections, reported Dr. Tam of the department of medicine and therapeutics at the Chinese University of Hong Kong. The researchers also observed a twofold increase in the overall incidence of high-risk HPV infection, compared with the low-risk type (11.6 per 1,000 patient-months vs. 5.4 per 1,000 patient-months, respectively).

“Other studies on healthy women found that 19%-38% of those [who] tested positive for HPV harbored multiple HPV types,” Dr. Tam said. “Such prevalence is much lower than that observed in our lupus cohort (65%).”

She went on to note that other studies on the natural history of cervical HPV infection in healthy subjects showed that most incident infections were transient, lasting less than 6 months. In contrast, the rate of persistent infection in this cohort of SLE patients appeared increased (49%).

The cumulative prevalence of multiple HPV infection also increased significantly (10/145 [6.9%] at baseline to 25/145 [17.2%] after 3 years, P = .007). The most common newly acquired high risk viral type was HPV-16 and-52 (1.7 per 1,000 patient-months), followed by HPV-18, −56 and −58 (1.2 per 1,000 patient-months).

In all, 20 out of 145 (13.8%) patients experienced at least one episode of persistent infection. The majority (overall infection: 34/69 [77.3%]; high-risk HPV: 23/30 [76.7%]; low-risk: 11/14 [8.6%]) of the incident HPV infections persisted for at least 6 months. Overall, 11/37 (29.7%) patients were able to clear all HPV infections.

Regarding the type-specific infections, the cohort participants cleared 33/38 (86.8%) of the pre-existing infections and 14/44 (31.8%) of all the incident infections.

The researchers also noticed that patients with high inflammatory burden as reflected by a SLICC/ACR (Systemic Lupus Erythematosus International Collaborating Clinics/American College of Rheumatology) Damage Index score of 1 or greater were at higher risk of acquiring HPV infection, after adjustment for the known risk factors as well as the use of immunosuppressants.

“In other reports of healthy young females, infection with high-risk types and multiple infections were risk factors for persistent infection,” Dr. Tam said. “In contrast, lupus patients with any HPV infections at baseline are at risk of having persistent infection regardless of risk type.” Independent risk factors associated with persistent HPV infection in SLE included preexisting HPV infection (P = .04) and multiple HPV infection during first incident infection (P = .02).

Independent risk factors associated with incident HPV infection included younger age at first sexual intercourse (P = .025; odds ratio, 0.868; 95% confidence interval, 0.766-0.983) and baseline SLICC =1 (P = .038; OR, 2.619; 95% CI, 1.054-6.508).

Independent risk factors associated with persistent HPV infection included pre-existing HPV infection at baseline (P < .001; OR, 89.47; 95% CI, 9.25-865.28) and multiple HPV infection during first incident infection (P < .001; OR, 188.11; 95% CI, 19.04-1858.42).

She acknowledged certain limitations of the study, including the lack of a healthy control group and the fact that that most of the patients in the study did not belong to the age group at highest risk for HPV.

The study was commissioned by the Food and Health Bureau of the Hong Kong SAR government, and was funded by the Research Fund for the Control of Infectious Diseases. This study was also supported by a Chinese University of Hong Kong research grant.

The cumulative prevalence of HPV infection increased from 12% at baseline to 25% after 3 years. DR. TAM

The rate of cervical human papillomavirus infection among women with systemic lupus erythematosus increased from 12% to 25% after 3 years, judging from results from a novel study presented at the annual European Congress of Rheumatology.

Moreover, patients were twice as likely to acquire high-risk HPV infection than low-risk HPV infection.

“Information about the natural history of HPV infection in SLE is lacking,” lead investigator Dr. Lai-Shan Tam said in an interview. “Whether immunosuppression related to SLE itself and/or the use of immunosuppressants would result in an increased incidence and risk of persistent HPV infection has never been studied.”

Dr. Tam and her associates evaluated 144 women with SLE at 6-month intervals for up to 3 years. During each visit, a Pap test, a test for HPV DNA, and a clinical assessment were performed in an effort to ascertain the incidence, clearance, and persistence of HPV infection. The mean age of the patients was 41 years, and mean disease duration was 8.6 years. The total duration of follow-up was 4,006 patient-months.

The cumulative prevalence of HPV infection increased from 12% at baseline to 25% after 3 years, and 19% of patients experienced a total of 69 incident infections, reported Dr. Tam of the department of medicine and therapeutics at the Chinese University of Hong Kong. The researchers also observed a twofold increase in the overall incidence of high-risk HPV infection, compared with the low-risk type (11.6 per 1,000 patient-months vs. 5.4 per 1,000 patient-months, respectively).

“Other studies on healthy women found that 19%-38% of those [who] tested positive for HPV harbored multiple HPV types,” Dr. Tam said. “Such prevalence is much lower than that observed in our lupus cohort (65%).”

She went on to note that other studies on the natural history of cervical HPV infection in healthy subjects showed that most incident infections were transient, lasting less than 6 months. In contrast, the rate of persistent infection in this cohort of SLE patients appeared increased (49%).

The cumulative prevalence of multiple HPV infection also increased significantly (10/145 [6.9%] at baseline to 25/145 [17.2%] after 3 years, P = .007). The most common newly acquired high risk viral type was HPV-16 and-52 (1.7 per 1,000 patient-months), followed by HPV-18, −56 and −58 (1.2 per 1,000 patient-months).

In all, 20 out of 145 (13.8%) patients experienced at least one episode of persistent infection. The majority (overall infection: 34/69 [77.3%]; high-risk HPV: 23/30 [76.7%]; low-risk: 11/14 [8.6%]) of the incident HPV infections persisted for at least 6 months. Overall, 11/37 (29.7%) patients were able to clear all HPV infections.

Regarding the type-specific infections, the cohort participants cleared 33/38 (86.8%) of the pre-existing infections and 14/44 (31.8%) of all the incident infections.

The researchers also noticed that patients with high inflammatory burden as reflected by a SLICC/ACR (Systemic Lupus Erythematosus International Collaborating Clinics/American College of Rheumatology) Damage Index score of 1 or greater were at higher risk of acquiring HPV infection, after adjustment for the known risk factors as well as the use of immunosuppressants.

“In other reports of healthy young females, infection with high-risk types and multiple infections were risk factors for persistent infection,” Dr. Tam said. “In contrast, lupus patients with any HPV infections at baseline are at risk of having persistent infection regardless of risk type.” Independent risk factors associated with persistent HPV infection in SLE included preexisting HPV infection (P = .04) and multiple HPV infection during first incident infection (P = .02).

Independent risk factors associated with incident HPV infection included younger age at first sexual intercourse (P = .025; odds ratio, 0.868; 95% confidence interval, 0.766-0.983) and baseline SLICC =1 (P = .038; OR, 2.619; 95% CI, 1.054-6.508).

Independent risk factors associated with persistent HPV infection included pre-existing HPV infection at baseline (P < .001; OR, 89.47; 95% CI, 9.25-865.28) and multiple HPV infection during first incident infection (P < .001; OR, 188.11; 95% CI, 19.04-1858.42).

She acknowledged certain limitations of the study, including the lack of a healthy control group and the fact that that most of the patients in the study did not belong to the age group at highest risk for HPV.

The study was commissioned by the Food and Health Bureau of the Hong Kong SAR government, and was funded by the Research Fund for the Control of Infectious Diseases. This study was also supported by a Chinese University of Hong Kong research grant.

The cumulative prevalence of HPV infection increased from 12% at baseline to 25% after 3 years. DR. TAM

The rate of cervical human papillomavirus infection among women with systemic lupus erythematosus increased from 12% to 25% after 3 years, judging from results from a novel study presented at the annual European Congress of Rheumatology.

Moreover, patients were twice as likely to acquire high-risk HPV infection than low-risk HPV infection.

“Information about the natural history of HPV infection in SLE is lacking,” lead investigator Dr. Lai-Shan Tam said in an interview. “Whether immunosuppression related to SLE itself and/or the use of immunosuppressants would result in an increased incidence and risk of persistent HPV infection has never been studied.”

Dr. Tam and her associates evaluated 144 women with SLE at 6-month intervals for up to 3 years. During each visit, a Pap test, a test for HPV DNA, and a clinical assessment were performed in an effort to ascertain the incidence, clearance, and persistence of HPV infection. The mean age of the patients was 41 years, and mean disease duration was 8.6 years. The total duration of follow-up was 4,006 patient-months.

The cumulative prevalence of HPV infection increased from 12% at baseline to 25% after 3 years, and 19% of patients experienced a total of 69 incident infections, reported Dr. Tam of the department of medicine and therapeutics at the Chinese University of Hong Kong. The researchers also observed a twofold increase in the overall incidence of high-risk HPV infection, compared with the low-risk type (11.6 per 1,000 patient-months vs. 5.4 per 1,000 patient-months, respectively).

“Other studies on healthy women found that 19%-38% of those [who] tested positive for HPV harbored multiple HPV types,” Dr. Tam said. “Such prevalence is much lower than that observed in our lupus cohort (65%).”

She went on to note that other studies on the natural history of cervical HPV infection in healthy subjects showed that most incident infections were transient, lasting less than 6 months. In contrast, the rate of persistent infection in this cohort of SLE patients appeared increased (49%).

The cumulative prevalence of multiple HPV infection also increased significantly (10/145 [6.9%] at baseline to 25/145 [17.2%] after 3 years, P = .007). The most common newly acquired high risk viral type was HPV-16 and-52 (1.7 per 1,000 patient-months), followed by HPV-18, −56 and −58 (1.2 per 1,000 patient-months).

In all, 20 out of 145 (13.8%) patients experienced at least one episode of persistent infection. The majority (overall infection: 34/69 [77.3%]; high-risk HPV: 23/30 [76.7%]; low-risk: 11/14 [8.6%]) of the incident HPV infections persisted for at least 6 months. Overall, 11/37 (29.7%) patients were able to clear all HPV infections.

Regarding the type-specific infections, the cohort participants cleared 33/38 (86.8%) of the pre-existing infections and 14/44 (31.8%) of all the incident infections.

The researchers also noticed that patients with high inflammatory burden as reflected by a SLICC/ACR (Systemic Lupus Erythematosus International Collaborating Clinics/American College of Rheumatology) Damage Index score of 1 or greater were at higher risk of acquiring HPV infection, after adjustment for the known risk factors as well as the use of immunosuppressants.

“In other reports of healthy young females, infection with high-risk types and multiple infections were risk factors for persistent infection,” Dr. Tam said. “In contrast, lupus patients with any HPV infections at baseline are at risk of having persistent infection regardless of risk type.” Independent risk factors associated with persistent HPV infection in SLE included preexisting HPV infection (P = .04) and multiple HPV infection during first incident infection (P = .02).

Independent risk factors associated with incident HPV infection included younger age at first sexual intercourse (P = .025; odds ratio, 0.868; 95% confidence interval, 0.766-0.983) and baseline SLICC =1 (P = .038; OR, 2.619; 95% CI, 1.054-6.508).

Independent risk factors associated with persistent HPV infection included pre-existing HPV infection at baseline (P < .001; OR, 89.47; 95% CI, 9.25-865.28) and multiple HPV infection during first incident infection (P < .001; OR, 188.11; 95% CI, 19.04-1858.42).

She acknowledged certain limitations of the study, including the lack of a healthy control group and the fact that that most of the patients in the study did not belong to the age group at highest risk for HPV.

The study was commissioned by the Food and Health Bureau of the Hong Kong SAR government, and was funded by the Research Fund for the Control of Infectious Diseases. This study was also supported by a Chinese University of Hong Kong research grant.

The cumulative prevalence of HPV infection increased from 12% at baseline to 25% after 3 years. DR. TAM

NEW ORLEANS — Patients with type 2 diabetes who were treated with once-daily liraglutide experienced significantly greater improvements in glycemic control, compared with patients who were treated with twice-daily exenatide, results from an open-label, multicenter trial showed.

The findings of the Effect of Liraglutide or Exenatide Added to an Ongoing Treatment on Blood Glucose Control in Subjects With Type 2 Diabetes (LEAD-6) were reported at the annual scientific sessions of the American Diabetes Association by Dr. John B. Buse, chief of the division of endocrinology at the University of North Carolina, Chapel Hill. They were simultaneously published online (Lancet 2009 [doi:10.1016/S0140-6736(09)60659-0]).

Liraglutide is an investigational human glucagon-like peptide-1 (GLP-1) analogue, developed by Novo Nordisk Inc., that is undergoing Food and Drug Administration review for approval. Its proposed indication is as an adjunct to diet and exercise and for use in combination therapy with oral antidiabetic agents to improve glycemic control in patients with type 2 diabetes.

Exenatide (Byetta, Amylin Pharmaceuticals Inc.) is an exendin-based GLP-1 receptor agonist approved for use by people with type 2 diabetes who are unsuccessful in controlling their blood sugar levels. Both agents are delivered via subcutaneous injection.

Between August 2007 and April 2008, 464 patients aged 18-80 years with type 2 diabetes were randomized to receive liraglutide 1.8 mg once daily or exenatide 10 mcg twice daily at 132 office-based sites in 15 countries. Patients were eligible for the trial if their hemoblobin A1c levels were 7%-11%, if their body mass index was 45 kg/m2 or less, and if they were on maximally tolerated doses of metformin, sulfonylurea, or both.

The primary end point of LEAD-6 was the difference in HbA1c values between the two treatment groups from baseline to week 26.

At baseline, the mean age of the patients was 56 years, 92% were white, mean BMI was 33 kg/m2, and their mean HbA1c level was 8.2%. Of the 464 patients, 231 received exenatide and 233 received liraglutide.

At 26 weeks, the mean reduction in HbA1c was 1.12% among patients in the liraglutide group, compared with 0.79% among patients in the exenatide group, a statistically significant difference. In addition, significantly more patients in the liraglutide group achieved HbA1c levels of less than 7%, compared with their counterparts in the exenatide group (54% vs. 43%, respectively).

The researchers also found that patients in the liraglutide group achieved significantly greater drops in levels of fasting plasma glucose, compared with those in the exenatide group (1.61 mmol/L vs. 0.60 mmol/L). However, exenatide reduced plasma glucose levels more than did liraglutide after breakfast and dinner meals, which suggests that liraglutide exerts more of its effects in the premeal or fasting period.

Weight reductions in both groups were similar, at about 3 kg.

Both drugs were well tolerated, but patients in the liraglutide group experienced less persistent nausea and less frequent rates of hypoglycemia, compared with those in the exenatide group.

In a commentary accompanying the study, Dr. Christophe E.M. DeBlock and Dr. Luc F. Van Gaal of Antwerp University Hospital, Belgium, expressed concerns about FDA reports of increased rates of pancreatitis associated with liraglutide treatment. “Whether the association is causal and whether it is a class effect of GLP-1 analogues is not clear,” they wrote (Lancet 2009 [DOI:10.1016/S0140-6736(09)60942-9.]) “We recommend not to give GLP-1 analogues to patients at risk for pancreatitis (e.g., with cholecystolithiasis, alcoholism, or hypertriglyceridemia).”

The commentators also pointed to an FDA briefing noting that the risk rate of frequency of papillary thyroid cancer in patients taking liraglutide is 1.6% per 1,000 patient-years of exposure, compared with 0.6% per 1,000 patient-years of exposure in patients taking exenatide. They recommended that future long-term studies of the agents include careful monitoring of thyroid abnormalities.

At the meeting, Dr. Buse said that there were no signs of elevated calcitonin levels (a marker of medullary thyroid carcinoma) in the study participants. “The calcitonin levels were very low on average and indistinguishable between the two groups,” he said.

Dr. Buse disclosed that he has been an investigator, consultant, or speaker for several pharmaceutical companies, including Amylin and Novo Nordisk, the trial's sponsor. Dr. Van Gaal is an adviser to Novo Nordisk and Eli Lilly. Dr. DeBlock declared that he had no conflicts of interest.

Mean reduction in HbA1c was 1.12% in the liraglutide group, compared with 0.79% in the exenatide group. DR. BUSE

NEW ORLEANS — Patients with type 2 diabetes who were treated with once-daily liraglutide experienced significantly greater improvements in glycemic control, compared with patients who were treated with twice-daily exenatide, results from an open-label, multicenter trial showed.

The findings of the Effect of Liraglutide or Exenatide Added to an Ongoing Treatment on Blood Glucose Control in Subjects With Type 2 Diabetes (LEAD-6) were reported at the annual scientific sessions of the American Diabetes Association by Dr. John B. Buse, chief of the division of endocrinology at the University of North Carolina, Chapel Hill. They were simultaneously published online (Lancet 2009 [doi:10.1016/S0140-6736(09)60659-0]).

Liraglutide is an investigational human glucagon-like peptide-1 (GLP-1) analogue, developed by Novo Nordisk Inc., that is undergoing Food and Drug Administration review for approval. Its proposed indication is as an adjunct to diet and exercise and for use in combination therapy with oral antidiabetic agents to improve glycemic control in patients with type 2 diabetes.

Exenatide (Byetta, Amylin Pharmaceuticals Inc.) is an exendin-based GLP-1 receptor agonist approved for use by people with type 2 diabetes who are unsuccessful in controlling their blood sugar levels. Both agents are delivered via subcutaneous injection.

Between August 2007 and April 2008, 464 patients aged 18-80 years with type 2 diabetes were randomized to receive liraglutide 1.8 mg once daily or exenatide 10 mcg twice daily at 132 office-based sites in 15 countries. Patients were eligible for the trial if their hemoblobin A1c levels were 7%-11%, if their body mass index was 45 kg/m2 or less, and if they were on maximally tolerated doses of metformin, sulfonylurea, or both.

The primary end point of LEAD-6 was the difference in HbA1c values between the two treatment groups from baseline to week 26.

At baseline, the mean age of the patients was 56 years, 92% were white, mean BMI was 33 kg/m2, and their mean HbA1c level was 8.2%. Of the 464 patients, 231 received exenatide and 233 received liraglutide.

At 26 weeks, the mean reduction in HbA1c was 1.12% among patients in the liraglutide group, compared with 0.79% among patients in the exenatide group, a statistically significant difference. In addition, significantly more patients in the liraglutide group achieved HbA1c levels of less than 7%, compared with their counterparts in the exenatide group (54% vs. 43%, respectively).

The researchers also found that patients in the liraglutide group achieved significantly greater drops in levels of fasting plasma glucose, compared with those in the exenatide group (1.61 mmol/L vs. 0.60 mmol/L). However, exenatide reduced plasma glucose levels more than did liraglutide after breakfast and dinner meals, which suggests that liraglutide exerts more of its effects in the premeal or fasting period.

Weight reductions in both groups were similar, at about 3 kg.

Both drugs were well tolerated, but patients in the liraglutide group experienced less persistent nausea and less frequent rates of hypoglycemia, compared with those in the exenatide group.

In a commentary accompanying the study, Dr. Christophe E.M. DeBlock and Dr. Luc F. Van Gaal of Antwerp University Hospital, Belgium, expressed concerns about FDA reports of increased rates of pancreatitis associated with liraglutide treatment. “Whether the association is causal and whether it is a class effect of GLP-1 analogues is not clear,” they wrote (Lancet 2009 [DOI:10.1016/S0140-6736(09)60942-9.]) “We recommend not to give GLP-1 analogues to patients at risk for pancreatitis (e.g., with cholecystolithiasis, alcoholism, or hypertriglyceridemia).”

The commentators also pointed to an FDA briefing noting that the risk rate of frequency of papillary thyroid cancer in patients taking liraglutide is 1.6% per 1,000 patient-years of exposure, compared with 0.6% per 1,000 patient-years of exposure in patients taking exenatide. They recommended that future long-term studies of the agents include careful monitoring of thyroid abnormalities.

At the meeting, Dr. Buse said that there were no signs of elevated calcitonin levels (a marker of medullary thyroid carcinoma) in the study participants. “The calcitonin levels were very low on average and indistinguishable between the two groups,” he said.

Dr. Buse disclosed that he has been an investigator, consultant, or speaker for several pharmaceutical companies, including Amylin and Novo Nordisk, the trial's sponsor. Dr. Van Gaal is an adviser to Novo Nordisk and Eli Lilly. Dr. DeBlock declared that he had no conflicts of interest.

Mean reduction in HbA1c was 1.12% in the liraglutide group, compared with 0.79% in the exenatide group. DR. BUSE

NEW ORLEANS — Patients with type 2 diabetes who were treated with once-daily liraglutide experienced significantly greater improvements in glycemic control, compared with patients who were treated with twice-daily exenatide, results from an open-label, multicenter trial showed.

The findings of the Effect of Liraglutide or Exenatide Added to an Ongoing Treatment on Blood Glucose Control in Subjects With Type 2 Diabetes (LEAD-6) were reported at the annual scientific sessions of the American Diabetes Association by Dr. John B. Buse, chief of the division of endocrinology at the University of North Carolina, Chapel Hill. They were simultaneously published online (Lancet 2009 [doi:10.1016/S0140-6736(09)60659-0]).

Liraglutide is an investigational human glucagon-like peptide-1 (GLP-1) analogue, developed by Novo Nordisk Inc., that is undergoing Food and Drug Administration review for approval. Its proposed indication is as an adjunct to diet and exercise and for use in combination therapy with oral antidiabetic agents to improve glycemic control in patients with type 2 diabetes.

Exenatide (Byetta, Amylin Pharmaceuticals Inc.) is an exendin-based GLP-1 receptor agonist approved for use by people with type 2 diabetes who are unsuccessful in controlling their blood sugar levels. Both agents are delivered via subcutaneous injection.

Between August 2007 and April 2008, 464 patients aged 18-80 years with type 2 diabetes were randomized to receive liraglutide 1.8 mg once daily or exenatide 10 mcg twice daily at 132 office-based sites in 15 countries. Patients were eligible for the trial if their hemoblobin A1c levels were 7%-11%, if their body mass index was 45 kg/m2 or less, and if they were on maximally tolerated doses of metformin, sulfonylurea, or both.

The primary end point of LEAD-6 was the difference in HbA1c values between the two treatment groups from baseline to week 26.

At baseline, the mean age of the patients was 56 years, 92% were white, mean BMI was 33 kg/m2, and their mean HbA1c level was 8.2%. Of the 464 patients, 231 received exenatide and 233 received liraglutide.

At 26 weeks, the mean reduction in HbA1c was 1.12% among patients in the liraglutide group, compared with 0.79% among patients in the exenatide group, a statistically significant difference. In addition, significantly more patients in the liraglutide group achieved HbA1c levels of less than 7%, compared with their counterparts in the exenatide group (54% vs. 43%, respectively).

The researchers also found that patients in the liraglutide group achieved significantly greater drops in levels of fasting plasma glucose, compared with those in the exenatide group (1.61 mmol/L vs. 0.60 mmol/L). However, exenatide reduced plasma glucose levels more than did liraglutide after breakfast and dinner meals, which suggests that liraglutide exerts more of its effects in the premeal or fasting period.

Weight reductions in both groups were similar, at about 3 kg.

Both drugs were well tolerated, but patients in the liraglutide group experienced less persistent nausea and less frequent rates of hypoglycemia, compared with those in the exenatide group.

In a commentary accompanying the study, Dr. Christophe E.M. DeBlock and Dr. Luc F. Van Gaal of Antwerp University Hospital, Belgium, expressed concerns about FDA reports of increased rates of pancreatitis associated with liraglutide treatment. “Whether the association is causal and whether it is a class effect of GLP-1 analogues is not clear,” they wrote (Lancet 2009 [DOI:10.1016/S0140-6736(09)60942-9.]) “We recommend not to give GLP-1 analogues to patients at risk for pancreatitis (e.g., with cholecystolithiasis, alcoholism, or hypertriglyceridemia).”

The commentators also pointed to an FDA briefing noting that the risk rate of frequency of papillary thyroid cancer in patients taking liraglutide is 1.6% per 1,000 patient-years of exposure, compared with 0.6% per 1,000 patient-years of exposure in patients taking exenatide. They recommended that future long-term studies of the agents include careful monitoring of thyroid abnormalities.

At the meeting, Dr. Buse said that there were no signs of elevated calcitonin levels (a marker of medullary thyroid carcinoma) in the study participants. “The calcitonin levels were very low on average and indistinguishable between the two groups,” he said.

Dr. Buse disclosed that he has been an investigator, consultant, or speaker for several pharmaceutical companies, including Amylin and Novo Nordisk, the trial's sponsor. Dr. Van Gaal is an adviser to Novo Nordisk and Eli Lilly. Dr. DeBlock declared that he had no conflicts of interest.

Mean reduction in HbA1c was 1.12% in the liraglutide group, compared with 0.79% in the exenatide group. DR. BUSE

NEW ORLEANS — There were no differences in total mortality among patients with type 2 diabetes and stable coronary heart disease who underwent early coronary revascularization compared with those who underwent intensive medical therapy alone, results from a large 5-year trial showed.

However, those who underwent coronary artery bypass grafting (CABG) had significantly lower rates of major cardiovascular events compared with medical therapy alone, an association that was not seen among those who underwent percutaneous coronary intervention (PCI).

In addition, the Bypass Angioplasty Revascularization Investigation in Type 2 Diabetes (BARI 2D), which also studied two glucose-lowering strategies, found no difference in outcome whether the patients received insulin-providing or insulin-sensitizing therapy.

The trial results were presented by Dr. Trevor J. Orchard at the annual scientific sessions of the American Diabetes Association.

“I don't think our results will change [clinical] practice, except to reassure clinicians and patients alike that treatment with insulin sensitizers is a perfectly safe and reasonable approach,” Dr. Orchard, professor of epidemiology at the University of Pittsburgh Graduate School of Public Health, said during a press briefing about the study.

BARI 2D is the first randomized study conducted in patients with mild symptoms and stable ischemic heart disease to show a benefit of CABG in reducing major cardiovascular events, “which were primarily nonfatal myocardial infarction,” said cardiologist Robert L. Frye, chair of the trial and professor of cardiovascular medicine at the Mayo Clinic in Rochester, Minn.

During January 2001-March 2005, researchers in six countries enrolled 2,368 patients with type 2 diabetes and stable coronary artery disease who were candidates for elective PCI or CABG. Each patient was selected to either a CABG stratum group or to a PCI stratum group (N. Engl. J. Med. 2009;360:2503-15).

Of the 763 patients in the CABG stratum group, 385 were randomly assigned to medical therapy (194 to insulin provision and 191 to insulin sensitization) and 378 were randomly assigned to revascularization with CABG, with 190 and 188 assigned to receive insulin provision and sensitization, respectively.

Of the 1,605 patients in the PCI stratum group, 807 were randomly assigned to medical therapy (399 to insulin provision and 408 to insulin sensitization) and 798 were randomly assigned to revascularization with PCI, with 402 and 396 assigned to receive insulin provision and sensitization, respectively.

The study's primary end points were the rate of death and the rate of major cardiovascular events, defined as a composite of death, myocardial infarction, or stroke.

At the time of study entry, the mean age of patients was 64 years, 70% were male, and 66% were white. Mean HbA1c level was 7.7% and mean duration of diabetes was 10 years.

Dr. Orchard reported that at 5 years, there were no statistically significant differences in the rates of survival between the revascularization group and the medical therapy group (88.3% vs. 87.8%, respectively) nor between the insulin-sensitization group and the insulin-provision group (88.2% vs. 87.9%).

There also were no differences in the rates of freedom from major cardiovascular events between the revascularization group and the medical therapy group (77.2% vs. 75.9%, respectively) nor between the insulin-sensitization and insulin-provision groups (77.7% vs. 75.4%).

When the researchers analyzed data from the PCI stratum alone, they observed no statistically significant differences in the primary end points between the revascularization group and the medical therapy group.

However, when they analyzed data from the CABG stratum alone, the rate of major cardiovascular events was significantly lower in the revascularization group compared with the medical therapy group (22.4% vs. 30.5%, respectively). This benefit appeared to be greatest in those who underwent CABG and received insulin-sensitizing drugs.

The BARI 2D was supported by grants from the National Heart, Lung, and Blood Institute and the National Institute of Diabetes and Digestive and Kidney Diseases. Support was also provided by GlaxoSmithKline, Lantheus Medical Imaging, Astellas Pharma, Merck, Abbott Laboratories, Pfizer, MediSense, Bayer, Becton Dickinson, J.R. Carlson Labs, Centocor, Eli Lilly & Co., LipoScience, Novartis, and Novo Nordisk. Dr. Orchard has served on advisory boards and received consulting fees from several companies that make diabetes-related pharmaceuticals and products, and has an equity interest in Bristol-Myers-Squibb. Dr. Frye is on the advisory boards of Sanofi-Aventis and Schering-Plough.

Mortality was similar, but CABG had lower rates of major cardiovascular events than medical therapy. DR. ORCHARD

NEW ORLEANS — There were no differences in total mortality among patients with type 2 diabetes and stable coronary heart disease who underwent early coronary revascularization compared with those who underwent intensive medical therapy alone, results from a large 5-year trial showed.

However, those who underwent coronary artery bypass grafting (CABG) had significantly lower rates of major cardiovascular events compared with medical therapy alone, an association that was not seen among those who underwent percutaneous coronary intervention (PCI).

In addition, the Bypass Angioplasty Revascularization Investigation in Type 2 Diabetes (BARI 2D), which also studied two glucose-lowering strategies, found no difference in outcome whether the patients received insulin-providing or insulin-sensitizing therapy.

The trial results were presented by Dr. Trevor J. Orchard at the annual scientific sessions of the American Diabetes Association.

“I don't think our results will change [clinical] practice, except to reassure clinicians and patients alike that treatment with insulin sensitizers is a perfectly safe and reasonable approach,” Dr. Orchard, professor of epidemiology at the University of Pittsburgh Graduate School of Public Health, said during a press briefing about the study.

BARI 2D is the first randomized study conducted in patients with mild symptoms and stable ischemic heart disease to show a benefit of CABG in reducing major cardiovascular events, “which were primarily nonfatal myocardial infarction,” said cardiologist Robert L. Frye, chair of the trial and professor of cardiovascular medicine at the Mayo Clinic in Rochester, Minn.

During January 2001-March 2005, researchers in six countries enrolled 2,368 patients with type 2 diabetes and stable coronary artery disease who were candidates for elective PCI or CABG. Each patient was selected to either a CABG stratum group or to a PCI stratum group (N. Engl. J. Med. 2009;360:2503-15).

Of the 763 patients in the CABG stratum group, 385 were randomly assigned to medical therapy (194 to insulin provision and 191 to insulin sensitization) and 378 were randomly assigned to revascularization with CABG, with 190 and 188 assigned to receive insulin provision and sensitization, respectively.

Of the 1,605 patients in the PCI stratum group, 807 were randomly assigned to medical therapy (399 to insulin provision and 408 to insulin sensitization) and 798 were randomly assigned to revascularization with PCI, with 402 and 396 assigned to receive insulin provision and sensitization, respectively.

The study's primary end points were the rate of death and the rate of major cardiovascular events, defined as a composite of death, myocardial infarction, or stroke.

At the time of study entry, the mean age of patients was 64 years, 70% were male, and 66% were white. Mean HbA1c level was 7.7% and mean duration of diabetes was 10 years.

Dr. Orchard reported that at 5 years, there were no statistically significant differences in the rates of survival between the revascularization group and the medical therapy group (88.3% vs. 87.8%, respectively) nor between the insulin-sensitization group and the insulin-provision group (88.2% vs. 87.9%).

There also were no differences in the rates of freedom from major cardiovascular events between the revascularization group and the medical therapy group (77.2% vs. 75.9%, respectively) nor between the insulin-sensitization and insulin-provision groups (77.7% vs. 75.4%).

When the researchers analyzed data from the PCI stratum alone, they observed no statistically significant differences in the primary end points between the revascularization group and the medical therapy group.

However, when they analyzed data from the CABG stratum alone, the rate of major cardiovascular events was significantly lower in the revascularization group compared with the medical therapy group (22.4% vs. 30.5%, respectively). This benefit appeared to be greatest in those who underwent CABG and received insulin-sensitizing drugs.

The BARI 2D was supported by grants from the National Heart, Lung, and Blood Institute and the National Institute of Diabetes and Digestive and Kidney Diseases. Support was also provided by GlaxoSmithKline, Lantheus Medical Imaging, Astellas Pharma, Merck, Abbott Laboratories, Pfizer, MediSense, Bayer, Becton Dickinson, J.R. Carlson Labs, Centocor, Eli Lilly & Co., LipoScience, Novartis, and Novo Nordisk. Dr. Orchard has served on advisory boards and received consulting fees from several companies that make diabetes-related pharmaceuticals and products, and has an equity interest in Bristol-Myers-Squibb. Dr. Frye is on the advisory boards of Sanofi-Aventis and Schering-Plough.

Mortality was similar, but CABG had lower rates of major cardiovascular events than medical therapy. DR. ORCHARD

NEW ORLEANS — There were no differences in total mortality among patients with type 2 diabetes and stable coronary heart disease who underwent early coronary revascularization compared with those who underwent intensive medical therapy alone, results from a large 5-year trial showed.

However, those who underwent coronary artery bypass grafting (CABG) had significantly lower rates of major cardiovascular events compared with medical therapy alone, an association that was not seen among those who underwent percutaneous coronary intervention (PCI).

In addition, the Bypass Angioplasty Revascularization Investigation in Type 2 Diabetes (BARI 2D), which also studied two glucose-lowering strategies, found no difference in outcome whether the patients received insulin-providing or insulin-sensitizing therapy.

The trial results were presented by Dr. Trevor J. Orchard at the annual scientific sessions of the American Diabetes Association.

“I don't think our results will change [clinical] practice, except to reassure clinicians and patients alike that treatment with insulin sensitizers is a perfectly safe and reasonable approach,” Dr. Orchard, professor of epidemiology at the University of Pittsburgh Graduate School of Public Health, said during a press briefing about the study.

BARI 2D is the first randomized study conducted in patients with mild symptoms and stable ischemic heart disease to show a benefit of CABG in reducing major cardiovascular events, “which were primarily nonfatal myocardial infarction,” said cardiologist Robert L. Frye, chair of the trial and professor of cardiovascular medicine at the Mayo Clinic in Rochester, Minn.

During January 2001-March 2005, researchers in six countries enrolled 2,368 patients with type 2 diabetes and stable coronary artery disease who were candidates for elective PCI or CABG. Each patient was selected to either a CABG stratum group or to a PCI stratum group (N. Engl. J. Med. 2009;360:2503-15).

Of the 763 patients in the CABG stratum group, 385 were randomly assigned to medical therapy (194 to insulin provision and 191 to insulin sensitization) and 378 were randomly assigned to revascularization with CABG, with 190 and 188 assigned to receive insulin provision and sensitization, respectively.

Of the 1,605 patients in the PCI stratum group, 807 were randomly assigned to medical therapy (399 to insulin provision and 408 to insulin sensitization) and 798 were randomly assigned to revascularization with PCI, with 402 and 396 assigned to receive insulin provision and sensitization, respectively.

The study's primary end points were the rate of death and the rate of major cardiovascular events, defined as a composite of death, myocardial infarction, or stroke.

At the time of study entry, the mean age of patients was 64 years, 70% were male, and 66% were white. Mean HbA1c level was 7.7% and mean duration of diabetes was 10 years.

Dr. Orchard reported that at 5 years, there were no statistically significant differences in the rates of survival between the revascularization group and the medical therapy group (88.3% vs. 87.8%, respectively) nor between the insulin-sensitization group and the insulin-provision group (88.2% vs. 87.9%).

There also were no differences in the rates of freedom from major cardiovascular events between the revascularization group and the medical therapy group (77.2% vs. 75.9%, respectively) nor between the insulin-sensitization and insulin-provision groups (77.7% vs. 75.4%).

When the researchers analyzed data from the PCI stratum alone, they observed no statistically significant differences in the primary end points between the revascularization group and the medical therapy group.

However, when they analyzed data from the CABG stratum alone, the rate of major cardiovascular events was significantly lower in the revascularization group compared with the medical therapy group (22.4% vs. 30.5%, respectively). This benefit appeared to be greatest in those who underwent CABG and received insulin-sensitizing drugs.

The BARI 2D was supported by grants from the National Heart, Lung, and Blood Institute and the National Institute of Diabetes and Digestive and Kidney Diseases. Support was also provided by GlaxoSmithKline, Lantheus Medical Imaging, Astellas Pharma, Merck, Abbott Laboratories, Pfizer, MediSense, Bayer, Becton Dickinson, J.R. Carlson Labs, Centocor, Eli Lilly & Co., LipoScience, Novartis, and Novo Nordisk. Dr. Orchard has served on advisory boards and received consulting fees from several companies that make diabetes-related pharmaceuticals and products, and has an equity interest in Bristol-Myers-Squibb. Dr. Frye is on the advisory boards of Sanofi-Aventis and Schering-Plough.

Mortality was similar, but CABG had lower rates of major cardiovascular events than medical therapy. DR. ORCHARD

SAN DIEGO – The prevalence of headache disorders in patients referred to a sleep lab for sleep-disordered breathing was 70% and consisted primarily of morning headache, a study of more than 200 patients showed.

A relationship between headache disorders and sleep disorder has been described anecdotally in the medical literature for several decades, but this marks the largest-known prospective study to evaluate the association, Dr. Timothy M. Quast reported during a poster session at an international conference of the American Thoracic Society.

“There have been very few studies done on this topic,” said Dr. Quast of the Walter Reed Army Medical Center, Washington. “The ones that we did find were small, of 50-80 patients. We wanted to find out if there was something to this association, or if this is something anecdotal that's just been repeated for decades.”

He and his associates asked 219 consecutive patients undergoing an overnight polysomnography for diagnostic purposes to complete a brief questionnaire to evaluate whether or not headache disorders were present. Respondents who were affected by headache disorders were asked to complete a more detailed questionnaire to diagnose and characterize the condition.

After all patients underwent poly-somnography, the researchers conducted follow-up phone calls at 1- and 3-month intervals to evaluate compliance with their continuous positive airway pressure machine and the effect of CPAP on a comorbid headache disorder.

The mean age of the 219 patients was 44 years old, their mean body mass index was 30.4 kg/m

A total of 154 patients (70%) had a headache disorder present and 65 did not. Morning headache was most common type of headache disorder (55%), followed by tension type headache (49%), migraine headache (32%), and chronic daily headache (16%).

No polysomnography features were predictive of headache disorder, a finding that surprised Dr. Quast. “The patients who had headaches had better sleep indices,” he said. “They had less respiratory disturbances, woke up less frequently, and had fewer hypopneas or apneas. They didn't move as much in terms of periodic leg movement syndrome, and they actually had higher mean oxygen saturation levels. That's counterintuitive.”

The researchers also found that CPAP therapy appeared to improve headache symptoms among patients who were compliant with their CPAP machines. “This is another reason that patients need to be compliant with their CPAP, because their headache might actually go away,” he commented.

Patients with a headache disorder tended to be younger, compared with their counterparts who did not have a headache disorder. They also reported being were more depressed based on responses to the Patient Health Questionnaire-9 and more tired based on responses to the Epworth Sleepiness Scale. “There's something breaking out here, but we did not have the power to determine what makes these subpopulations different from one another,” Dr. Quast said.

He estimated that a study of at least 500 patients will be required to further elucidate the findings.

For now, he said, the clinical implications of the current findings are that if you have a patient that complains of waking up with a headache in the morning, “that's highly predictive of sleep disordered breathing, and that person should undergo a sleep study,” advised Dr. Quast, who had no conflicts to disclose.

To watch a video interview of Dr. Quast, go to www.youtube.com/ClinPsychNews

If a patient reports waking up with a headache, 'that's highly predictive of sleep disordered breathing.' DR. QUAST

SAN DIEGO – The prevalence of headache disorders in patients referred to a sleep lab for sleep-disordered breathing was 70% and consisted primarily of morning headache, a study of more than 200 patients showed.

A relationship between headache disorders and sleep disorder has been described anecdotally in the medical literature for several decades, but this marks the largest-known prospective study to evaluate the association, Dr. Timothy M. Quast reported during a poster session at an international conference of the American Thoracic Society.

“There have been very few studies done on this topic,” said Dr. Quast of the Walter Reed Army Medical Center, Washington. “The ones that we did find were small, of 50-80 patients. We wanted to find out if there was something to this association, or if this is something anecdotal that's just been repeated for decades.”

He and his associates asked 219 consecutive patients undergoing an overnight polysomnography for diagnostic purposes to complete a brief questionnaire to evaluate whether or not headache disorders were present. Respondents who were affected by headache disorders were asked to complete a more detailed questionnaire to diagnose and characterize the condition.

After all patients underwent poly-somnography, the researchers conducted follow-up phone calls at 1- and 3-month intervals to evaluate compliance with their continuous positive airway pressure machine and the effect of CPAP on a comorbid headache disorder.

The mean age of the 219 patients was 44 years old, their mean body mass index was 30.4 kg/m

A total of 154 patients (70%) had a headache disorder present and 65 did not. Morning headache was most common type of headache disorder (55%), followed by tension type headache (49%), migraine headache (32%), and chronic daily headache (16%).

No polysomnography features were predictive of headache disorder, a finding that surprised Dr. Quast. “The patients who had headaches had better sleep indices,” he said. “They had less respiratory disturbances, woke up less frequently, and had fewer hypopneas or apneas. They didn't move as much in terms of periodic leg movement syndrome, and they actually had higher mean oxygen saturation levels. That's counterintuitive.”

The researchers also found that CPAP therapy appeared to improve headache symptoms among patients who were compliant with their CPAP machines. “This is another reason that patients need to be compliant with their CPAP, because their headache might actually go away,” he commented.

Patients with a headache disorder tended to be younger, compared with their counterparts who did not have a headache disorder. They also reported being were more depressed based on responses to the Patient Health Questionnaire-9 and more tired based on responses to the Epworth Sleepiness Scale. “There's something breaking out here, but we did not have the power to determine what makes these subpopulations different from one another,” Dr. Quast said.

He estimated that a study of at least 500 patients will be required to further elucidate the findings.

For now, he said, the clinical implications of the current findings are that if you have a patient that complains of waking up with a headache in the morning, “that's highly predictive of sleep disordered breathing, and that person should undergo a sleep study,” advised Dr. Quast, who had no conflicts to disclose.

To watch a video interview of Dr. Quast, go to www.youtube.com/ClinPsychNews

If a patient reports waking up with a headache, 'that's highly predictive of sleep disordered breathing.' DR. QUAST

SAN DIEGO – The prevalence of headache disorders in patients referred to a sleep lab for sleep-disordered breathing was 70% and consisted primarily of morning headache, a study of more than 200 patients showed.

A relationship between headache disorders and sleep disorder has been described anecdotally in the medical literature for several decades, but this marks the largest-known prospective study to evaluate the association, Dr. Timothy M. Quast reported during a poster session at an international conference of the American Thoracic Society.

“There have been very few studies done on this topic,” said Dr. Quast of the Walter Reed Army Medical Center, Washington. “The ones that we did find were small, of 50-80 patients. We wanted to find out if there was something to this association, or if this is something anecdotal that's just been repeated for decades.”

He and his associates asked 219 consecutive patients undergoing an overnight polysomnography for diagnostic purposes to complete a brief questionnaire to evaluate whether or not headache disorders were present. Respondents who were affected by headache disorders were asked to complete a more detailed questionnaire to diagnose and characterize the condition.

After all patients underwent poly-somnography, the researchers conducted follow-up phone calls at 1- and 3-month intervals to evaluate compliance with their continuous positive airway pressure machine and the effect of CPAP on a comorbid headache disorder.

The mean age of the 219 patients was 44 years old, their mean body mass index was 30.4 kg/m

A total of 154 patients (70%) had a headache disorder present and 65 did not. Morning headache was most common type of headache disorder (55%), followed by tension type headache (49%), migraine headache (32%), and chronic daily headache (16%).

No polysomnography features were predictive of headache disorder, a finding that surprised Dr. Quast. “The patients who had headaches had better sleep indices,” he said. “They had less respiratory disturbances, woke up less frequently, and had fewer hypopneas or apneas. They didn't move as much in terms of periodic leg movement syndrome, and they actually had higher mean oxygen saturation levels. That's counterintuitive.”

The researchers also found that CPAP therapy appeared to improve headache symptoms among patients who were compliant with their CPAP machines. “This is another reason that patients need to be compliant with their CPAP, because their headache might actually go away,” he commented.

Patients with a headache disorder tended to be younger, compared with their counterparts who did not have a headache disorder. They also reported being were more depressed based on responses to the Patient Health Questionnaire-9 and more tired based on responses to the Epworth Sleepiness Scale. “There's something breaking out here, but we did not have the power to determine what makes these subpopulations different from one another,” Dr. Quast said.

He estimated that a study of at least 500 patients will be required to further elucidate the findings.

For now, he said, the clinical implications of the current findings are that if you have a patient that complains of waking up with a headache in the morning, “that's highly predictive of sleep disordered breathing, and that person should undergo a sleep study,” advised Dr. Quast, who had no conflicts to disclose.

To watch a video interview of Dr. Quast, go to www.youtube.com/ClinPsychNews

If a patient reports waking up with a headache, 'that's highly predictive of sleep disordered breathing.' DR. QUAST