What Can We Learn From GLP-1 Receptor Agonist Studies on Weight Loss?

Is weight loss with GLP-1 receptor agonists permanent? Can they be used in binge eating disorder or after bariatric surgery? In this commentary, I answer these and other questions from learners who participated in the webinar, “Ushering in a New Era of Sustainable Weight Loss With Incretin-Based Therapies.”

Is weight loss sustained after stopping treatment with a GLP-1 receptor agonist? Will rapid weight gain occur?
Unfortunately, the weight loss benefit of GLP-1 receptor agonists does go away when you stop the medication. Patients can regain some or all of the weight they lose.

The STEP 4 withdrawal trial compared the effect on body weight of continuing once-weekly treatment with subcutaneous semaglutide (2.4 mg) vs switching to placebo (both with lifestyle intervention) in adults with overweight or obesity.

After a 20-week run-in period with a mean weight loss of 10.6%, participants who were randomized to continue semaglutide for 48 more weeks continued to lose weight (-7.9%), whereas those randomized to switch to placebo gradually regained 6.9% of the weight between Week 20 and Week 68.

These results are similar to results from the follow-up phase of the SCALE Maintenance trial of liraglutide vs placebo (both with lifestyle intervention), where participants lost weight during the 56-week treatment phase but then regained some weight during the 12-week post-drug discontinuation follow-up.

What do these semaglutide and liraglutide trial results tell us? They tell us that obesity is a chronic disease. We should look at obesity treatment the same way we look at hypertension or hyperlipidemia treatment. If you stop taking antihypertensive medications, your blood pressure will go up again; if you stop taking a GLP-1 receptor agonist, your weight will go up again.

How long can we treat patients with liraglutide for weight loss?
Although the double-blind period of the SCALE Maintenance trial was 56 weeks, the longer 3-year evaluation in the SCALE Obesity and Prediabetes trial showed that liraglutide was more effective than placebo in reducing type 2 diabetes risk and body weight in individuals with obesity and prediabetes. However, only 50% of participants completed the study up to Week 160.

Whereas data demonstrating long-term (>3 years) benefits of sustained weight loss are scant, ongoing monitoring of weight loss responses and adverse events is necessary to determine the optimal treatment duration for individual patients.

Regardless of how long treatment lasts, weight loss pharmacotherapy should be considered as an adjunct therapy to lifestyle modification. Liraglutide is approved by the FDA for chronic weight management along with a reduced calorie diet and increased physical activity.

Can GLP-1 receptor agonistsbe used after bariatric surgery?
Several studies evaluating the effect of GLP-1 receptor agonists in weight management after bariatric/metabolic surgery have recently been published.

In a retrospective study, Wharton and colleagues found that in patients who experienced insufficient weight loss—or excessive weight regain—after metabolic surgery, treatment with 3.0 mg liraglutide led to significant weight loss from baseline regardless of bariatric surgery type. No placebo control was included in this study.

Separately, in a randomized, double-blind, placebo-controlled study in individuals with obesity, Thakur and colleagues found that increasing doses of liraglutide (0.6 mg to 3.0 mg daily) between 6 weeks and 6 months post-laparoscopic sleeve gastrectomy (LSG) significantly augmented weight loss from LSG.

And in the randomized, double-blind, placebo-controlled GRAVITAS trial in patients with persistent or recurrent type 2 diabetes after metabolic surgery, Miras and colleagues found that adjunctive liraglutide treatment was more effective than placebo in reducing A1C and body weight.

Overall, these findings support the adjunctive use of an approved GLP-1 receptor agonist after metabolic surgery in patients who do not reach their weight loss goals, patients who experience weight regain, or patients with persistent or recurrent type 2 diabetes.

Is liraglutide effective in patients with binge eating disorder?
Currently, there are very limited data on the use of GLP-1 receptor agonists in patients with binge eating disorder.

In a small (N = 44), randomized trial comparing liraglutide 1.8 mg/day plus diet and exercise for 12 weeks vs diet and exercise only, liraglutide was associated with reductions in body weight, blood pressure, fasting glucose, and scores on the binge eating scale.

Larger, longer, and more rigorously designed studies are needed to evaluate the effect of GLP-1 receptor agonists on binge eating disorder or other eating disorders.

Your Thoughts
What are your thoughts on the use of GLP-1 receptor agonists to maintain weight loss after bariatric surgery or in patients with binge eating disorder? Answer the polling question and share your thoughts in the comments box below.