Semaglutide As The Next Obesity Medication?

Semaglutide is an analog of the human hormone GLP-1, which is a hormone that our intestines release when we eat. This hormone tells our brains we feel full, can reduce food cravings, and helps the pancreas to control blood sugar by increasing insulin release and suppressing a hormone called glucagon.

We know semaglutide well as the diabetes medication Ozempic, which has been available in Canada since early 2018 for the treatment of type 2 diabetes at a dose of 1 mg weekly. In addition to improving blood sugars in people with type 2 diabetes, it also causes weight loss.

Semaglutide has now been studied comprehensively as an obesity treatment at a higher dose of 2.4mg weekly, for people with or without type 2 diabetes. In 2018, we published the phase 2 study results. The STEP program is the name of the much larger phase 3 clinical trial program that has studied semaglutide as an obesity treatment. In the last month, press releases have been issued on the four STEP trials, and the results are impressive:

STEP 1: After 68 weeks, people with obesity (or overweight with related health issues) treated with semaglutide 2.4mg weekly achieved 14.9% weight loss, vs 2.4% weight loss with placebo. Those who took the medication as intended (ie they were able to titrate it up on the typical schedule and stayed on it for the whole trial) lost 16.9% weight.

STEP 2: (Disclaimer: I am an investigator in this study) In people with type 2 diabetes and either obesity or overweight, people in the semaglutide 2.4mg weekly group lost 9.6% weight, vs 7.0% weight with semaglutide 1mg (Ozempic), vs 3.4% weight on placebo, after 68 weeks. Those who took semaglutide 2.4mg weekly as intended lost 10.6% weight. (Note that the weight loss in people with diabetes in this trial is less than the weight loss seen in STEP 1 above, which was in people without diabetes. This is typical, in that people with type 2 diabetes have a more difficult time losing weight than people without diabetes).

STEP 3: In addition to intensive behavioral therapy, people with obesity (or overweight with related health issues) on semaglutide 2.4mg weekly achieved 16.0% weight loss vs 5.7% weight loss with placebo at 68 weeks. Those who took semaglutide 2.4mg weekly as intended lost 17.6% weight.

STEP 4: In this study, people with obesity (or overweight with related health issues) were all given semaglutide 2.4mg for 20 weeks. Those who reached the full dose of 2.4mg were then randomized to continued treatment vs placebo for another 48 weeks. Those who continued semaglutide lost a total of 17.4% weight. Those who were randomized to placebo regained most of the weight they had lost when originally on semaglutide.

In all of the STEP studies, semaglutide 2.4mg appeared to have a safe and well-tolerated profile, with the most common issue being gastrointestinal upset, mostly mild to moderate in severity (this is a known side effect of the GLP1 medication class).

So, it seems that the future is very bright for semaglutide as an obesity treatment. The degree of weight loss seen in the STEP trials markedly exceeds the weight loss seen with any other currently available obesity medication. None of these studies have been peer-reviewed or published yet, but we can look forward to these papers in the coming months. Once these papers are published, regulatory agencies around the world (including FDA and Health Canada) will review for potential approval for use.

Disclaimer: I am an investigator in the STEP 2 study. All studies are conducted by Novo Nordisk, the makers of semaglutide. I receive honoraria as a continuing medical education speaker and consultant from Novo Nordisk.

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