With millions of people now using GLP-1 drugs such as Wegovy and Zepbound, scientists are racing to find ways to help people retain their weight loss after they stop taking the medication

By Jackie Flynn Mogensen edited by Claire Cameron

An estimated one in eight American adults are taking GLP-1 (glucagonlike peptide 1) drugs including Wegovy and Zepbound to treat conditions such as diabetes or to lose weight. Some experts believe that some people will need to take these medications for life to retain their results. But research suggests most of these individuals will quit the drugs—and when people do so, most of their weight tends to come back. The same is true for those who lose weight by dieting—after the diet ends, they typically regain the weight.

Now a pair of independent clinical trials point to two possible methods for preventing weight regain: taking a daily oral GLP-1 drug called orforglipron or taking a supplement that contains a pasteurized strain of Akkermansia muciniphila bacteria. Both studies were published on Tuesday in the journal Nature Medicine.

In the orforglipron study, which was funded by the drug’s maker, Eli Lily, researchers conducted a controlled trial that followed more than 370 people who had been injecting either semaglutide (which is sold under brand names such as Ozempic and Wegovy) or tirzepatide (sold as Mounjaro and Zepbound). After 72 weeks on one of these drugs, the participants switched to a daily orforglipron pill or a placebo.

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After around a year, the participants who had gone on orforglipron tended to maintain more of their weight loss—about 79 percent of what they had lost on semaglutide and 75 percent of what they’d lost on tirzepatide—than the placebo group. People who had been assigned the placebo, meanwhile, maintained about 38 percent of the weight they’d lost on semaglutide and about 49 percent of what they'd lost on tirzepatide.

The findings suggest that it is “feasible” to switch from a once-weekly injection to a once-daily GLP-1 tablet “with fairly good preservation of initial weight loss,” says Daniel Drucker, a university professor of medicine at the University of Toronto, who has previously consulted for Eli Lilly but was not involved in the trial. “These findings offer more options for some people who might prefer a once-daily tablet versus a once-weekly injection,” he says.

Drucker notes, however, that orforglipron (which is sold under the brand name Foundayo) was only recently approved by the U.S. Food and Drug Administration in April and that there is “much less” safety data for orforglipron than there is for injectable forms of semaglutide and tirzepatide.

In the second clinical trial, researchers tracked 84 adults who lost weight on an eight-week-long, low-calorie regimen and were then randomly assigned to take an A. muciniphila supplement or a placebo while eating a regular balanced diet.

After about six months, the researchers found that the group taking the A. muciniphila supplement regained less weight on average and ended the study with a total weight loss of about three kilograms more than those not taking the supplement. (The study was funded by the Akkermansia Company, which manufacturers an A. muciniphila supplement.)

The results are “interesting,” but “the effect size is quite modest,” so it’s unclear how much the treatment would translate to real-world use, Drucker says.

There is some precedent for using A. muciniphila for weight-loss maintenance, says Ellen Blaak, the second study’s senior author and a professor of human biology at Maastricht University in the Netherlands. (Blaak is a scientific adviser for the Akkermansia Company and is an inventor on a patent application related to the study.) The bacteria had been shown to aid in weight loss in animal studies and one small human trial. Until now, it hadn’t been tested for weight-loss maintenance in a longer-term randomized clinical trial.

Weight regain after dieting or even after using GLP-1s is the “most important problem” in obesity management, Blaak says—and the results indicate that A. muciniphila could be a “tool” to help combat that, she argues. “Most individuals succeed in losing weight at certain moments in their life.... This would be helpful to keep that weight off,” Blaak says.

In the future, Blaak says, her research team hopes to follow patients for longer than six months and to investigate whether naturally occurring levels of A. muciniphila in a person’s gut may play a role in their weight loss, as well as to research other potential microbial treatments. “There are many possibilities,” she says.