Obesity Week 2014

BOSTON – Moderately obese patients who either don’t want or don’t qualify for bariatric surgery may be able to benefit from a reversible procedure using an investigational intragastric balloon.

In a randomized controlled trial, patients with a body mass index (BMI) from 30 to 40 kg/m² who were assigned to receive a dual intragastric balloon (ReShape Duo) plus a diet and exercise regimen lost 25% of their excess weight, compared with only 11% of patients assigned to undergo a sham procedure plus diet and exercise, reported Dr. Jaime Ponce, medical director for the Bariatric Surgery program at Hamilton Medical Center in Dalton, Ga., and Memorial Hospital in Chattanooga, Tenn.

Neil Osterweil/Frontline Medical News

“The ReShape procedure is a reversible intervention that can be used in patients with BMI from 30 to 40 who are not ready for surgery or did not qualify for surgery. It was effective, as it showed a 2.2 times greater weight loss, compared with the diet group,” he said at the meeting presented by the Obesity Society and the American Society for Metabolic and Bariatric Surgery.

At 48 weeks, patients sustained on average 65% of the weight loss they had achieved at week 24, he said.

Two-chamber device

The dual intragastric balloon consists of two silicone balloons connected by a flexible shaft to provide migration resistance. The deflated device is inserted over a guide wire into the stomach in a transoral endoscopic procedure. Once in place, the device is inflated with a saline and methylene blue solution by a powered pump, up to a total volume of 750 to 900 cc. The mean duration of the procedure is 8 minutes Dr. Ponce said.

Barring problems, the device is left in place for 6 months and is then emptied, captured with a standard endoscopic snare, and removed, a process that takes a mean of 14 minutes.

Dr. Ponce and colleagues enrolled obese adults with a BMD from 30 to 40 kg/m² and one or more obesity-related comorbidities to undergo either balloon insertion, diet and exercise (187 patients), or a sham procedure plus diet and exercise (139).

All patients had monthly counseling on diet and exercise as per obesity management guidelines from the National Heart, Lung and Blood Institute published in 2000.

The participants were blinded to treatment assignment for 24 weeks, at which time patients in the diet group could exit the study or, if they wished, receive the balloon and continue in the study for an additional 24 weeks. Patients who initially received the balloon remained in the study and continued diet and exercise during the same 24 weeks.

Balloons were successfully inserted in 99.6% of cases, and all inserted balloons were retrieved successfully. Three patients had serious adverse events related to retrieval: one case of pneumonia requiring hospitalization and antibiotics, one contained perforation of the cervical esophagus, also requiring hospitalization and antibiotics, and one proximal esophageal mucosal tear requiring hemostatic clips.

The trial met its primary endpoint of a greater than 7.5% difference between the balloon and control groups, with balloon receivers having a mean excess weight loss of 25.1%, compared with 11.3% for controls (P = .0041) in an intention to treat analysis, and 27.9% vs. 12.3%, respectively, in patients who completed the study (P = .0007).

At 48 weeks, patients initially assigned to receive the balloon had significant improvements in hemoglobin A_1c, cholesterol levels (HDL up, LDL down), systolic and diastolic blood pressures, and waist and hip circumference.

Among all implanted participants, 11.6% had mild to moderate nausea and vomiting on day 3, which gradually declined over the study. In addition, 34.1% had abdominal pain they rated as mild to moderate on a visual analog scale,

The safety analysis, including all 264 patients who received the balloon initially or at week 24, showed no deaths, balloon migration, obstructions, or required surgeries. Most adverse events were gastrointestinal in nature, mild to moderate, and resolved within the first 30 days.

Investigators saw gastric ulcers in 93 of the 264 patients who received the balloon. They determined the cause to be the distal tip of the device contacting the incisural wall, where more than 95% of the ulcers were observed. The manufacturer made minor changes to lower the profile of the tip and make it smoother and softer, resulting a “dramatically reduced ulcer rate and size,” Dr. Ponce said.

In all, 15% of the balloons were retrieved early, 6% after 2 months, associated with ulcers, and 9% within 2 months of insertions because of device intolerance. The authors found shorter patients had significantly fewer problems when the balloons were inflated with 750 cc rather than 900 cc.

The balloons spontaneously deflated in 6% of participants, signaled by the presence of blue-green urine in about two-thirds of these patients. All of the devices in these cases were successfully retrieved without problems, Dr. Ponce said.

Dr. Manoel P. Galvao Neto of the Gastro Obeso Center in São Paulo, Brazil, the invited discussant, commented that the study was well designed and carried out, with a clear methodology and frank assessment of adverse events, and it met all of its primary endpoints.

Excretable balloon

In a separate pilot study, eight patients who swallowed a limited-duration, self-emptying balloon (Elipse) that is excreted through the bowel lost an average of 12% of excess body weight, reported Dr. Evzen Machytka of the department of clinical studies at the University of Ostrava, Czech Republic.

For the trial, investigators used a custom device designed to self-deflate in 6 weeks. The device is packaged in a capsule and is attached to a thin capillary tube. The patient swallows the balloon without endoscopy or anesthesia. The capsule dissolves quickly, and when gastric positioning of the balloon is confirmed with x-rays, the balloon is then filled with 450 mL saline, in a process that takes approximately 15 minutes.

After a prespecified time (6 weeks, in the case of the trial, 3 months in the device intended for market) a self-releasing valve opens, the balloon empties and is then excreted normally, Dr. Machytka said.

In the pilot trial, all eight balloons were safely excreted. One had deflated early because of a manufacturing defect, and one asymptomatic patient withdrew from the study because she “no longer enjoyed eating.” In both cases, the balloons were punctured via endoscopy but not retrieved, and were excreted normally in the stool 4 days later.

The investigators hope to receive marketing approval for the device in 2015, Dr. Machytka said.

BOSTON – Moderately obese patients who either don’t want or don’t qualify for bariatric surgery may be able to benefit from a reversible procedure using an investigational intragastric balloon.

In a randomized controlled trial, patients with a body mass index (BMI) from 30 to 40 kg/m² who were assigned to receive a dual intragastric balloon (ReShape Duo) plus a diet and exercise regimen lost 25% of their excess weight, compared with only 11% of patients assigned to undergo a sham procedure plus diet and exercise, reported Dr. Jaime Ponce, medical director for the Bariatric Surgery program at Hamilton Medical Center in Dalton, Ga., and Memorial Hospital in Chattanooga, Tenn.

Neil Osterweil/Frontline Medical News

“The ReShape procedure is a reversible intervention that can be used in patients with BMI from 30 to 40 who are not ready for surgery or did not qualify for surgery. It was effective, as it showed a 2.2 times greater weight loss, compared with the diet group,” he said at the meeting presented by the Obesity Society and the American Society for Metabolic and Bariatric Surgery.

At 48 weeks, patients sustained on average 65% of the weight loss they had achieved at week 24, he said.

Two-chamber device

The dual intragastric balloon consists of two silicone balloons connected by a flexible shaft to provide migration resistance. The deflated device is inserted over a guide wire into the stomach in a transoral endoscopic procedure. Once in place, the device is inflated with a saline and methylene blue solution by a powered pump, up to a total volume of 750 to 900 cc. The mean duration of the procedure is 8 minutes Dr. Ponce said.

Barring problems, the device is left in place for 6 months and is then emptied, captured with a standard endoscopic snare, and removed, a process that takes a mean of 14 minutes.

Dr. Ponce and colleagues enrolled obese adults with a BMD from 30 to 40 kg/m² and one or more obesity-related comorbidities to undergo either balloon insertion, diet and exercise (187 patients), or a sham procedure plus diet and exercise (139).

All patients had monthly counseling on diet and exercise as per obesity management guidelines from the National Heart, Lung and Blood Institute published in 2000.

The participants were blinded to treatment assignment for 24 weeks, at which time patients in the diet group could exit the study or, if they wished, receive the balloon and continue in the study for an additional 24 weeks. Patients who initially received the balloon remained in the study and continued diet and exercise during the same 24 weeks.

Balloons were successfully inserted in 99.6% of cases, and all inserted balloons were retrieved successfully. Three patients had serious adverse events related to retrieval: one case of pneumonia requiring hospitalization and antibiotics, one contained perforation of the cervical esophagus, also requiring hospitalization and antibiotics, and one proximal esophageal mucosal tear requiring hemostatic clips.

The trial met its primary endpoint of a greater than 7.5% difference between the balloon and control groups, with balloon receivers having a mean excess weight loss of 25.1%, compared with 11.3% for controls (P = .0041) in an intention to treat analysis, and 27.9% vs. 12.3%, respectively, in patients who completed the study (P = .0007).

At 48 weeks, patients initially assigned to receive the balloon had significant improvements in hemoglobin A_1c, cholesterol levels (HDL up, LDL down), systolic and diastolic blood pressures, and waist and hip circumference.

Among all implanted participants, 11.6% had mild to moderate nausea and vomiting on day 3, which gradually declined over the study. In addition, 34.1% had abdominal pain they rated as mild to moderate on a visual analog scale,

The safety analysis, including all 264 patients who received the balloon initially or at week 24, showed no deaths, balloon migration, obstructions, or required surgeries. Most adverse events were gastrointestinal in nature, mild to moderate, and resolved within the first 30 days.

Investigators saw gastric ulcers in 93 of the 264 patients who received the balloon. They determined the cause to be the distal tip of the device contacting the incisural wall, where more than 95% of the ulcers were observed. The manufacturer made minor changes to lower the profile of the tip and make it smoother and softer, resulting a “dramatically reduced ulcer rate and size,” Dr. Ponce said.

In all, 15% of the balloons were retrieved early, 6% after 2 months, associated with ulcers, and 9% within 2 months of insertions because of device intolerance. The authors found shorter patients had significantly fewer problems when the balloons were inflated with 750 cc rather than 900 cc.

The balloons spontaneously deflated in 6% of participants, signaled by the presence of blue-green urine in about two-thirds of these patients. All of the devices in these cases were successfully retrieved without problems, Dr. Ponce said.

Dr. Manoel P. Galvao Neto of the Gastro Obeso Center in São Paulo, Brazil, the invited discussant, commented that the study was well designed and carried out, with a clear methodology and frank assessment of adverse events, and it met all of its primary endpoints.

Excretable balloon

In a separate pilot study, eight patients who swallowed a limited-duration, self-emptying balloon (Elipse) that is excreted through the bowel lost an average of 12% of excess body weight, reported Dr. Evzen Machytka of the department of clinical studies at the University of Ostrava, Czech Republic.

For the trial, investigators used a custom device designed to self-deflate in 6 weeks. The device is packaged in a capsule and is attached to a thin capillary tube. The patient swallows the balloon without endoscopy or anesthesia. The capsule dissolves quickly, and when gastric positioning of the balloon is confirmed with x-rays, the balloon is then filled with 450 mL saline, in a process that takes approximately 15 minutes.

After a prespecified time (6 weeks, in the case of the trial, 3 months in the device intended for market) a self-releasing valve opens, the balloon empties and is then excreted normally, Dr. Machytka said.

In the pilot trial, all eight balloons were safely excreted. One had deflated early because of a manufacturing defect, and one asymptomatic patient withdrew from the study because she “no longer enjoyed eating.” In both cases, the balloons were punctured via endoscopy but not retrieved, and were excreted normally in the stool 4 days later.

The investigators hope to receive marketing approval for the device in 2015, Dr. Machytka said.

BOSTON – Moderately obese patients who either don’t want or don’t qualify for bariatric surgery may be able to benefit from a reversible procedure using an investigational intragastric balloon.

In a randomized controlled trial, patients with a body mass index (BMI) from 30 to 40 kg/m² who were assigned to receive a dual intragastric balloon (ReShape Duo) plus a diet and exercise regimen lost 25% of their excess weight, compared with only 11% of patients assigned to undergo a sham procedure plus diet and exercise, reported Dr. Jaime Ponce, medical director for the Bariatric Surgery program at Hamilton Medical Center in Dalton, Ga., and Memorial Hospital in Chattanooga, Tenn.

Neil Osterweil/Frontline Medical News

“The ReShape procedure is a reversible intervention that can be used in patients with BMI from 30 to 40 who are not ready for surgery or did not qualify for surgery. It was effective, as it showed a 2.2 times greater weight loss, compared with the diet group,” he said at the meeting presented by the Obesity Society and the American Society for Metabolic and Bariatric Surgery.

At 48 weeks, patients sustained on average 65% of the weight loss they had achieved at week 24, he said.

Two-chamber device

The dual intragastric balloon consists of two silicone balloons connected by a flexible shaft to provide migration resistance. The deflated device is inserted over a guide wire into the stomach in a transoral endoscopic procedure. Once in place, the device is inflated with a saline and methylene blue solution by a powered pump, up to a total volume of 750 to 900 cc. The mean duration of the procedure is 8 minutes Dr. Ponce said.

Barring problems, the device is left in place for 6 months and is then emptied, captured with a standard endoscopic snare, and removed, a process that takes a mean of 14 minutes.

Dr. Ponce and colleagues enrolled obese adults with a BMD from 30 to 40 kg/m² and one or more obesity-related comorbidities to undergo either balloon insertion, diet and exercise (187 patients), or a sham procedure plus diet and exercise (139).

All patients had monthly counseling on diet and exercise as per obesity management guidelines from the National Heart, Lung and Blood Institute published in 2000.

The participants were blinded to treatment assignment for 24 weeks, at which time patients in the diet group could exit the study or, if they wished, receive the balloon and continue in the study for an additional 24 weeks. Patients who initially received the balloon remained in the study and continued diet and exercise during the same 24 weeks.

Balloons were successfully inserted in 99.6% of cases, and all inserted balloons were retrieved successfully. Three patients had serious adverse events related to retrieval: one case of pneumonia requiring hospitalization and antibiotics, one contained perforation of the cervical esophagus, also requiring hospitalization and antibiotics, and one proximal esophageal mucosal tear requiring hemostatic clips.

The trial met its primary endpoint of a greater than 7.5% difference between the balloon and control groups, with balloon receivers having a mean excess weight loss of 25.1%, compared with 11.3% for controls (P = .0041) in an intention to treat analysis, and 27.9% vs. 12.3%, respectively, in patients who completed the study (P = .0007).

At 48 weeks, patients initially assigned to receive the balloon had significant improvements in hemoglobin A_1c, cholesterol levels (HDL up, LDL down), systolic and diastolic blood pressures, and waist and hip circumference.

Among all implanted participants, 11.6% had mild to moderate nausea and vomiting on day 3, which gradually declined over the study. In addition, 34.1% had abdominal pain they rated as mild to moderate on a visual analog scale,

The safety analysis, including all 264 patients who received the balloon initially or at week 24, showed no deaths, balloon migration, obstructions, or required surgeries. Most adverse events were gastrointestinal in nature, mild to moderate, and resolved within the first 30 days.

Investigators saw gastric ulcers in 93 of the 264 patients who received the balloon. They determined the cause to be the distal tip of the device contacting the incisural wall, where more than 95% of the ulcers were observed. The manufacturer made minor changes to lower the profile of the tip and make it smoother and softer, resulting a “dramatically reduced ulcer rate and size,” Dr. Ponce said.

In all, 15% of the balloons were retrieved early, 6% after 2 months, associated with ulcers, and 9% within 2 months of insertions because of device intolerance. The authors found shorter patients had significantly fewer problems when the balloons were inflated with 750 cc rather than 900 cc.

The balloons spontaneously deflated in 6% of participants, signaled by the presence of blue-green urine in about two-thirds of these patients. All of the devices in these cases were successfully retrieved without problems, Dr. Ponce said.

Dr. Manoel P. Galvao Neto of the Gastro Obeso Center in São Paulo, Brazil, the invited discussant, commented that the study was well designed and carried out, with a clear methodology and frank assessment of adverse events, and it met all of its primary endpoints.

Excretable balloon

In a separate pilot study, eight patients who swallowed a limited-duration, self-emptying balloon (Elipse) that is excreted through the bowel lost an average of 12% of excess body weight, reported Dr. Evzen Machytka of the department of clinical studies at the University of Ostrava, Czech Republic.

For the trial, investigators used a custom device designed to self-deflate in 6 weeks. The device is packaged in a capsule and is attached to a thin capillary tube. The patient swallows the balloon without endoscopy or anesthesia. The capsule dissolves quickly, and when gastric positioning of the balloon is confirmed with x-rays, the balloon is then filled with 450 mL saline, in a process that takes approximately 15 minutes.

After a prespecified time (6 weeks, in the case of the trial, 3 months in the device intended for market) a self-releasing valve opens, the balloon empties and is then excreted normally, Dr. Machytka said.

In the pilot trial, all eight balloons were safely excreted. One had deflated early because of a manufacturing defect, and one asymptomatic patient withdrew from the study because she “no longer enjoyed eating.” In both cases, the balloons were punctured via endoscopy but not retrieved, and were excreted normally in the stool 4 days later.

The investigators hope to receive marketing approval for the device in 2015, Dr. Machytka said.

BOSTON – Further parsing of data from the SCALE clinical trials reinforces the finding that an investigational dose of liraglutide, combined with diet and exercise, is linked with more weight loss in obese diabetic and nondiabetic adults than diet and exercise alone, albeit with significant GI adverse effects.

Among patients who completed the 56-week SCALE Obesity and Prediabetes trial, obese and prediabetic adults treated with an investigational 3-mg injectable daily dose of liraglutide plus calorie restriction and exercise lost a mean of 9.2% of their body weight, compared with 3.5% for patients who injected themselves with placebo and also dieted and exercised.

“Liraglutide 3 mg, in obese patients with prediabetes and without prediabetes, gave significantly more weight loss than in the placebo group, and it was independent of whether or not patients had prediabetes, or their body mass index,” Dr. Frank Greenway of the Pennington Biomedical Research Center in Baton Rouge, La., said at Obesity Week 2014, presented by the Obesity Society and the American Society for Metabolic and Bariatric Surgery.

Patients with a baseline BMI of up to 29.9 kg/m² lost an average of 7.5% of body weight, those with a BMI of 30-34.9 lost 8.3%, those with a BMI of 35-39.9% dropped 9.3% on average, and those with BMIs of 40 or over shed 7.4%. In each category, the difference between the liraglutide and placebo groups was significant (P < .0001).

Liraglutide is a glucagon-like peptide-1 (GLP-1) analogue approved in the United States as a 1.2-mg and 1.8-mg daily subcutaneous injection as an adjunct to diet and exercise in patients with type 2 diabetes. It is not recommended as first-line therapy for patients with diabetes that is not adequately controlled with diet and exercise. On the basis of the results of the SCALE trials and others, advisers to the Food and Drug Administration in September recommended that the 3-mg dose be approved for weight management in adults. At press time, no decision on the application by the manufacturer, Novo Nordisk, had been made by the FDA.

The SCALE trial enrolled 3,731 patients and randomized them on a 2:1 basis to liraglutide (2,487) or placebo (1,244).

GI adverse events common

The most common adverse event with liraglutide over the course of the study was nausea, which occurred in 40% of patients who injected the drug, compared with 15% of patients who injected a placebo. Diarrhea occurred in 21% and 9%., respectively, and vomiting occurred in 16% and 4%.

Despite these adverse events, which tended to peak by the 6th to 8th week of the study, more patients in the placebo group dropped out of the study (28.1% vs. 35.6%), said Dr. Ken Fujioka of the department of nutrition and metabolic research at the Scripps Clinic in La Jolla, Calif.

“This is a high rate of nausea,” Dr. Fujioka said. He noted that the trial protocol required an upward dose titration that could not be reversed without causing the patient to exit the study, which could partially explain the high rate of gastrointestinal distress seen with the drug.

Dr. Fujioka reported health-related quality of life data from the trial, based on scores in the Short Form–36 (SF-36) and Impact of Weight on Quality of Life–Lite (IWQoL-Lite) questionnaires, which showed better, albeit modest, gains over baselines in patients on liraglutide compared with placebo.

Liraglutide in diabetes patients

Dr. Robert F. Kushner of Northwestern University, Chicago, reported results from a separate trial from the SCALE clinical trial series, SCALE-Diabetes, looking at health-related quality of life in 846 overweight or obese patients with type 2 diabetes treated with liraglutide at the investigational 3-mg dose, the approved 1.8-mg dose, or placebo. All patients also engaged in calorie restriction and exercise.

At week 56, the mean body weight percentage lost from baseline was 5.9% in the 3-mg group, 4.6% in the 1.8 mg group, and 2% in the placebo group.

Compared with placebo, there was a significantly better mean total improvement in the IWQoL-Lite score with the 3-mg dose but not with the 1.8-mg dose. Gastrointestinal adverse events also were common in this trial, with nausea occurring in 33% on the 3-mg dose, 31% on the 1.8-mg dose, and 14% of patients on placebo. Diarrhea occurred in 26%, 18%, and 13%, respectively, and constipation in 16%, 10%, and 6%.

“The nausea that is seen in this trial primarily occurs from the first 12-16 weeks and then settles down, and there is not that much difference thereafter,” Dr. Kushner said.

Too expensive?

An obesity researcher who was not involved in the study noted that liraglutide is not yet reimbursed for weight loss, and has an adverse event profile that may discourage some patients from remaining on the drug.

“I think that for those people who can tolerate the medication and who can afford it, it’s better than placebo. If you can have access to medication it’s great, but a lot of people are not able to stick to it for any duration of time, and that’s the downside of it. If you don’t stick to it, the weight comes back,” Dr. Ranjan Sudan, a surgeon at Duke University, Durham, N.C., and chair of the ASMBS Research Committee, said in an interview.

“If this medication, for instance, could show that down the road it prevented or prolonged the onset of diabetes, that would be a whole different thing, and there may be some justification for its use. But for the moment, being primarily for weight loss purposes and not to treat comorbidities makes it a little bit of a hard sell,” he said.

If approved, liraglutide 3 mg will be marketed as Saxenda. Liraglutide 1.8 mg was approved in 2010 and is marketed as Victoza.

The studies were supported by Novo Nordisk. Dr. Greenway and Dr. Kushner disclosed serving on the company’s advisory board. Dr. Fujioka disclosed receiving research support and consulting with the company.

BOSTON – Further parsing of data from the SCALE clinical trials reinforces the finding that an investigational dose of liraglutide, combined with diet and exercise, is linked with more weight loss in obese diabetic and nondiabetic adults than diet and exercise alone, albeit with significant GI adverse effects.

Among patients who completed the 56-week SCALE Obesity and Prediabetes trial, obese and prediabetic adults treated with an investigational 3-mg injectable daily dose of liraglutide plus calorie restriction and exercise lost a mean of 9.2% of their body weight, compared with 3.5% for patients who injected themselves with placebo and also dieted and exercised.

“Liraglutide 3 mg, in obese patients with prediabetes and without prediabetes, gave significantly more weight loss than in the placebo group, and it was independent of whether or not patients had prediabetes, or their body mass index,” Dr. Frank Greenway of the Pennington Biomedical Research Center in Baton Rouge, La., said at Obesity Week 2014, presented by the Obesity Society and the American Society for Metabolic and Bariatric Surgery.

Patients with a baseline BMI of up to 29.9 kg/m² lost an average of 7.5% of body weight, those with a BMI of 30-34.9 lost 8.3%, those with a BMI of 35-39.9% dropped 9.3% on average, and those with BMIs of 40 or over shed 7.4%. In each category, the difference between the liraglutide and placebo groups was significant (P < .0001).

Liraglutide is a glucagon-like peptide-1 (GLP-1) analogue approved in the United States as a 1.2-mg and 1.8-mg daily subcutaneous injection as an adjunct to diet and exercise in patients with type 2 diabetes. It is not recommended as first-line therapy for patients with diabetes that is not adequately controlled with diet and exercise. On the basis of the results of the SCALE trials and others, advisers to the Food and Drug Administration in September recommended that the 3-mg dose be approved for weight management in adults. At press time, no decision on the application by the manufacturer, Novo Nordisk, had been made by the FDA.

The SCALE trial enrolled 3,731 patients and randomized them on a 2:1 basis to liraglutide (2,487) or placebo (1,244).

GI adverse events common

The most common adverse event with liraglutide over the course of the study was nausea, which occurred in 40% of patients who injected the drug, compared with 15% of patients who injected a placebo. Diarrhea occurred in 21% and 9%., respectively, and vomiting occurred in 16% and 4%.

Despite these adverse events, which tended to peak by the 6th to 8th week of the study, more patients in the placebo group dropped out of the study (28.1% vs. 35.6%), said Dr. Ken Fujioka of the department of nutrition and metabolic research at the Scripps Clinic in La Jolla, Calif.

“This is a high rate of nausea,” Dr. Fujioka said. He noted that the trial protocol required an upward dose titration that could not be reversed without causing the patient to exit the study, which could partially explain the high rate of gastrointestinal distress seen with the drug.

Dr. Fujioka reported health-related quality of life data from the trial, based on scores in the Short Form–36 (SF-36) and Impact of Weight on Quality of Life–Lite (IWQoL-Lite) questionnaires, which showed better, albeit modest, gains over baselines in patients on liraglutide compared with placebo.

Liraglutide in diabetes patients

Dr. Robert F. Kushner of Northwestern University, Chicago, reported results from a separate trial from the SCALE clinical trial series, SCALE-Diabetes, looking at health-related quality of life in 846 overweight or obese patients with type 2 diabetes treated with liraglutide at the investigational 3-mg dose, the approved 1.8-mg dose, or placebo. All patients also engaged in calorie restriction and exercise.

At week 56, the mean body weight percentage lost from baseline was 5.9% in the 3-mg group, 4.6% in the 1.8 mg group, and 2% in the placebo group.

Compared with placebo, there was a significantly better mean total improvement in the IWQoL-Lite score with the 3-mg dose but not with the 1.8-mg dose. Gastrointestinal adverse events also were common in this trial, with nausea occurring in 33% on the 3-mg dose, 31% on the 1.8-mg dose, and 14% of patients on placebo. Diarrhea occurred in 26%, 18%, and 13%, respectively, and constipation in 16%, 10%, and 6%.

“The nausea that is seen in this trial primarily occurs from the first 12-16 weeks and then settles down, and there is not that much difference thereafter,” Dr. Kushner said.

Too expensive?

An obesity researcher who was not involved in the study noted that liraglutide is not yet reimbursed for weight loss, and has an adverse event profile that may discourage some patients from remaining on the drug.

“I think that for those people who can tolerate the medication and who can afford it, it’s better than placebo. If you can have access to medication it’s great, but a lot of people are not able to stick to it for any duration of time, and that’s the downside of it. If you don’t stick to it, the weight comes back,” Dr. Ranjan Sudan, a surgeon at Duke University, Durham, N.C., and chair of the ASMBS Research Committee, said in an interview.

“If this medication, for instance, could show that down the road it prevented or prolonged the onset of diabetes, that would be a whole different thing, and there may be some justification for its use. But for the moment, being primarily for weight loss purposes and not to treat comorbidities makes it a little bit of a hard sell,” he said.

If approved, liraglutide 3 mg will be marketed as Saxenda. Liraglutide 1.8 mg was approved in 2010 and is marketed as Victoza.

The studies were supported by Novo Nordisk. Dr. Greenway and Dr. Kushner disclosed serving on the company’s advisory board. Dr. Fujioka disclosed receiving research support and consulting with the company.

BOSTON – Further parsing of data from the SCALE clinical trials reinforces the finding that an investigational dose of liraglutide, combined with diet and exercise, is linked with more weight loss in obese diabetic and nondiabetic adults than diet and exercise alone, albeit with significant GI adverse effects.

Among patients who completed the 56-week SCALE Obesity and Prediabetes trial, obese and prediabetic adults treated with an investigational 3-mg injectable daily dose of liraglutide plus calorie restriction and exercise lost a mean of 9.2% of their body weight, compared with 3.5% for patients who injected themselves with placebo and also dieted and exercised.

“Liraglutide 3 mg, in obese patients with prediabetes and without prediabetes, gave significantly more weight loss than in the placebo group, and it was independent of whether or not patients had prediabetes, or their body mass index,” Dr. Frank Greenway of the Pennington Biomedical Research Center in Baton Rouge, La., said at Obesity Week 2014, presented by the Obesity Society and the American Society for Metabolic and Bariatric Surgery.

Patients with a baseline BMI of up to 29.9 kg/m² lost an average of 7.5% of body weight, those with a BMI of 30-34.9 lost 8.3%, those with a BMI of 35-39.9% dropped 9.3% on average, and those with BMIs of 40 or over shed 7.4%. In each category, the difference between the liraglutide and placebo groups was significant (P < .0001).

Liraglutide is a glucagon-like peptide-1 (GLP-1) analogue approved in the United States as a 1.2-mg and 1.8-mg daily subcutaneous injection as an adjunct to diet and exercise in patients with type 2 diabetes. It is not recommended as first-line therapy for patients with diabetes that is not adequately controlled with diet and exercise. On the basis of the results of the SCALE trials and others, advisers to the Food and Drug Administration in September recommended that the 3-mg dose be approved for weight management in adults. At press time, no decision on the application by the manufacturer, Novo Nordisk, had been made by the FDA.

The SCALE trial enrolled 3,731 patients and randomized them on a 2:1 basis to liraglutide (2,487) or placebo (1,244).

GI adverse events common

The most common adverse event with liraglutide over the course of the study was nausea, which occurred in 40% of patients who injected the drug, compared with 15% of patients who injected a placebo. Diarrhea occurred in 21% and 9%., respectively, and vomiting occurred in 16% and 4%.

Despite these adverse events, which tended to peak by the 6th to 8th week of the study, more patients in the placebo group dropped out of the study (28.1% vs. 35.6%), said Dr. Ken Fujioka of the department of nutrition and metabolic research at the Scripps Clinic in La Jolla, Calif.

“This is a high rate of nausea,” Dr. Fujioka said. He noted that the trial protocol required an upward dose titration that could not be reversed without causing the patient to exit the study, which could partially explain the high rate of gastrointestinal distress seen with the drug.

Dr. Fujioka reported health-related quality of life data from the trial, based on scores in the Short Form–36 (SF-36) and Impact of Weight on Quality of Life–Lite (IWQoL-Lite) questionnaires, which showed better, albeit modest, gains over baselines in patients on liraglutide compared with placebo.

Liraglutide in diabetes patients

Dr. Robert F. Kushner of Northwestern University, Chicago, reported results from a separate trial from the SCALE clinical trial series, SCALE-Diabetes, looking at health-related quality of life in 846 overweight or obese patients with type 2 diabetes treated with liraglutide at the investigational 3-mg dose, the approved 1.8-mg dose, or placebo. All patients also engaged in calorie restriction and exercise.

At week 56, the mean body weight percentage lost from baseline was 5.9% in the 3-mg group, 4.6% in the 1.8 mg group, and 2% in the placebo group.

Compared with placebo, there was a significantly better mean total improvement in the IWQoL-Lite score with the 3-mg dose but not with the 1.8-mg dose. Gastrointestinal adverse events also were common in this trial, with nausea occurring in 33% on the 3-mg dose, 31% on the 1.8-mg dose, and 14% of patients on placebo. Diarrhea occurred in 26%, 18%, and 13%, respectively, and constipation in 16%, 10%, and 6%.

“The nausea that is seen in this trial primarily occurs from the first 12-16 weeks and then settles down, and there is not that much difference thereafter,” Dr. Kushner said.

Too expensive?

An obesity researcher who was not involved in the study noted that liraglutide is not yet reimbursed for weight loss, and has an adverse event profile that may discourage some patients from remaining on the drug.

“I think that for those people who can tolerate the medication and who can afford it, it’s better than placebo. If you can have access to medication it’s great, but a lot of people are not able to stick to it for any duration of time, and that’s the downside of it. If you don’t stick to it, the weight comes back,” Dr. Ranjan Sudan, a surgeon at Duke University, Durham, N.C., and chair of the ASMBS Research Committee, said in an interview.

“If this medication, for instance, could show that down the road it prevented or prolonged the onset of diabetes, that would be a whole different thing, and there may be some justification for its use. But for the moment, being primarily for weight loss purposes and not to treat comorbidities makes it a little bit of a hard sell,” he said.

If approved, liraglutide 3 mg will be marketed as Saxenda. Liraglutide 1.8 mg was approved in 2010 and is marketed as Victoza.

The studies were supported by Novo Nordisk. Dr. Greenway and Dr. Kushner disclosed serving on the company’s advisory board. Dr. Fujioka disclosed receiving research support and consulting with the company.