Weight gain after stopping GLP-1 drugs (by Patricia Toro, MD MPH)

November 21, 2023

This post guest-authored by my colleague Patricia Toro, MD MPH

Source: Rubino, et al JAMA March, 2021 LINK

The GLP-1 drug class has been shown to be effective at supporting weight loss, from an average of 15% for Wegovy (semaglutide) to 21% for the newly- approved Zepbound (tirzepatide). This amount of weight loss is similar to bariatric surgery outcomes. The FDA approvals of these GLP-1 medications do not suggest any end date for either medication. A key question that still has no answer is: Can individuals stop taking a GLP-1 medication and maintain their weight loss?

When individuals lose weight, particularly the large amounts of weight seen with GLP-1s, their bodies try to “defend” their original weight. Humans have a complex set of hormones that regulate weight. The balance of those hormones increase hunger and decrease metabolism when weight goes down dramatically. Better nutritional and exercise habits can certainly support weight loss, but current data suggests that weight loss is not sustained once the drugs are stopped, even with nutritional support.

A 2021 study published in JAMA evaluated 803 individuals on semaglutide with monthly nutritional support. The group lost, on average, 10.6% of their body weight at 20 weeks. They then switched a third of the group to receive a placebo for the next 48 weeks, while the rest continued semaglutide. Throughout the entire 68-week trial, both groups received lifestyle support, including diet counseling, exercise support, and in-person or virtual counseling visits at least monthly. The placebo group regained almost half of the lost weight, while the treatment group lost an average of 17.4% of their initial weight by the completion of the trial.

Implications for employers:

• This study shows that those who discontinue GLP-1s regain a substantial portion of the weight they had lost even with ongoing nutritional counseling .

• Vendors that claim that they can successfully “wean” patients from GLP-1s should be prepared to share published data on these outcomes, as current data does not support this claim.

• There is little evidence to guide time or dollar limits on GLP-1s, and we don’t know if long-term use of GLP-1s would allow successful stopping in the future.

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Next post will be on Monday, November 27. Hope you and yours have a wonderful Thanksgiving!