COMMENTARY

Updates on Semaglutide for Weight Loss, From ENDO 2021

Anne L. Peters, MD

Disclosures

April 20, 2021

This transcript has been edited for clarity.

At the 2021 Endocrine Society meeting, an update to the STEP trials was presented. For those of you who don't remember what the STEP trials are, they are four different trials looking at the benefits of semaglutide for weight loss in people with and without diabetes. The trial included people who were 18 years or older with a BMI ≥ 30 kg/m2 in the absence of a weight-related preexisting condition, or BMI ≥ 27 kg/m2 if they did have a preexisting condition.

Breaking Down the Trials

STEP 1, which was recently published in The New England Journal of Medicine, looked at a dose of 2.4 mg semaglutide and lifestyle intervention in patients with obesity who didn't have diabetes. Many of my patients saw this study as a headline and many of them wanted to go on semaglutide immediately. They didn't realize that they'd already been on semaglutide, but just at the lower 1-mg dose that is currently FDA-approved for the treatment of type 2 diabetes.

STEP 2 is for [2.4 mg] semaglutide and lifestyle intervention in individuals with type 2 diabetes and obesity. STEP 3 is also 2.4 mg semaglutide in conjunction with intensive behavioral therapy in adults with obesity. And STEP 4 is looking at the value of continued semaglutide usage.

The published findings from STEP 1 show that 2.4 mg of semaglutide was associated with a weight loss of 14.9% from a baseline of 232 lb compared with 2.4% in the placebo group after 68 weeks. One of the impressive things about their data is that you really did see weight loss continue to persist at least through 1 year, and then it did not go back up. This was a gradual, slow weight loss over time.

Eighty-six percent of the participants in the semaglutide group reached a weight loss of 5% or more compared with 32% on placebo. In terms of absolute numbers, the absolute weight loss was 15.3 kg (which is almost 34 lb) in adults without diabetes compared with 2.6 kg in the placebo group.

In terms of side effects, as we know, the most common side effects of GLP-1 receptor agonists are gastrointestinal; 4.5% of the participants discontinued because of the gastrointestinal side effects compared with 0.8% in the placebo group.

Body Composition and Baseline Characteristics

An abstract presented at the Endocrine Society meeting looked at changes in body composition. They found a 3.5% reduction in total fat mass and a 2% reduction in visceral fat — which is great, because we obviously want people to lose visceral fat. But their total lean body mass decreased by 10%. That's a fairly large fall in lean body mass.

This finding was mitigated by the fact that the ratio of lean body mass to fat mass improved slightly. But it really brings home the point that we need patients to work on the physical activity portion of lifestyle change as they lose weight. I want to make sure that people are aware that just because they're taking a medication for weight loss, that doesn't mean they don't have to do other things, like exercise, in order to become healthier.

Another abstract looked at [patients'] baseline characteristics and tried to relate them to success at weight loss. Pretty consistently across all groups, there was a nice reduction in weight. The percentage of weight loss was greater in female participants, which makes me smile slightly because in many of our weight loss interventions, we've seen that they work better in men than in women; but in these trials, it was better in the women.

Those who had a lower body weight at baseline lost more weight than those who had a higher weight. So, everybody lost weight, but if you were a bit leaner — and remember, all of these individuals had obesity — you were more likely to lose a bit more weight and get closer to the target weight.

Those are the updates for the STEP studies. We're going to hear a lot more in the next year or so. Then, obviously, there needs to be FDA approval of semaglutide for weight loss and, finally, reimbursement, so we can provide it to our patients. Thank you.

Anne L. Peters, MD, is a professor of medicine at the University of Southern California (USC) Keck School of Medicine and director of the USC clinical diabetes programs. She has published more than 200 articles, reviews, and abstracts, and three books, on diabetes, and has been an investigator for more than 40 research studies. She has spoken internationally at over 400 programs and serves on many committees of several professional organizations.

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