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Adding a GLP-1 receptor agonist to intensive behavioral therapy (IBT) helped bolster weight loss, the found.

Among 611 adults with overweight or obesity, those who added 2.4 mg of once-weekly subcutaneous semaglutide to IBT lost significantly more weight than those on behavioral therapy alone, reported Thomas Wadden, PhD, of the University of Pennsylvania in Philadelphia.

After 68 weeks, those on semaglutide plus IBT lost an average of 16% of baseline body weight, while those on placebo plus IBT only lost about 5.7% (estimated treatment difference [ETD] -10.3, 95% CI -12.0 to -8.6, P<0.0001), Wadden explained during a presentation at the Obesity Society's virtual ObesityWeek Interactive.

Also meeting the trial's co-primary endpoint, those on semaglutide plus IBT achieved significantly greater benchmarks of baseline body weight lost versus IBT alone:

• Achieved 5% or more of weight lost: 87% vs 48% on IBT alone
• 10% or more of weight lost: 75% vs 27%
• 15% or more of weight lost: 56% vs 13%
• 20% or more of weight lost: 36% vs 4%

"With greater weight loss, you expect greater reductions in CVD risk factors, and that's exactly what was observed," Wadden said.

Specifically, those on semaglutide plus IBT saw a 14.6-cm reduction in waist circumference compared with a 6.3-cm reduction with IBT alone (ETD -8.3 cm, 95% CI -10.1 to -6.6, P<0.0001).

Even though all participants were euglycemic at baseline, those on semaglutide still had a significant drop in HbA1c levels -- dropping 0.51% versus a drop of 0.27% in the comparator arm (ETD -0.24%, 95% CI -0.29% to -0.19%, P<0.0001).

Participants on semaglutide also saw a significantly greater reduction in blood pressure, achieving a 5.6 mm Hg drop in systolic blood pressure and a 3 mm Hg drop in diastolic blood pressure. However, there was an increase in pulse among those on semaglutide, particularly during the first 16 weeks of treatment, but this slowly decreased over the course of the trial. At the end of week 68, this difference was no longer significant, with an increase of 3.1 beats/min for those on semaglutide versus an increase of 2.1 beats/min for IBT alone.

Measuring inflammation, C-reactive protein levels also significantly improved among those on semaglutide, with an estimated drop of 60% compared with a drop of 23% for those on IBT alone (4.46 mg/dL mean at baseline; estimated relative difference -48%, 95% CI -55% to -39%, P<0.0001).

This isn't the first agent in this class to show this weight loss effect, as a previous trial also led by Wadden found 3.0 mg of liraglutide added to IBT also yielded significantly greater weight loss than IBT alone.

Among the 611 adults included in the study, average body weight was 234 lb (106 kg), with a BMI of 38, and most were women. For inclusion, participants had to have a BMI of 27 or higher, with at least one comorbidity, or obesity with a BMI of 30 or greater. All participants were free of diabetes at baseline, with an HbA1c under 6.5%.

With a 2:1 randomization, the 407 participants who received semaglutide started on a 16-week dose escalation phase leading to a 52-week maintenance phase of weekly 2.4-mg semaglutide injections. Wadden pointed out that this 2.4-mg dose used in the study is a higher dose of semaglutide than the 1.0-mg dose already approved for type 2 diabetes.

All participants also underwent 30 15-minute IBT sessions delivered by a registered dietitian aimed at bolstering exercise and reducing calorie intake. This included an initial 8-week low-calorie meal replacement diet to jump-start weight loss, which was comprised of 1,000-1,200 calories per day of liquid meals, meal bars, and portion-controlled conventional foods. Thereafter, a hypocaloric diet was followed for the remainder of the trial, with a daily threshold of less than 1,200 or 1,800 calories for those with a baseline weight under 200 lbs or 300 lbs, respectively.

Everyone was also guided to achieve 100 minutes per week of moderate-intensity exercise, which increased by 15 minutes every 4 weeks.

As expected, this higher dose of semaglutide also came with a greater incidence of gastrointestinal adverse events, mainly comprised of nausea, vomiting, diarrhea, and constipation (83% vs 63% for IBT alone). There was also a higher rate of serious adverse events among the semaglutide group (9% vs 3%), which was mainly due to complications with gallbladder function -- the development of gallstones or requiring a cholecystectomy.

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