A new class of weight-loss drug just took a major step toward approval for use. In a phase 3 clinical trial, the medication retatrutide helped control blood sugar levels in participants with type 2 diabetes and led to an average of up to 36.6 pounds of weight loss, according to drugmaker Eli Lilly.
Retatrutide is among an emerging generation of weight loss drugs called GLP-3 agonists. While GLP-1 (glucagonlike peptide 1) agonist drugs such as semaglutide target a single hormone receptor that regulates hunger, GLP-3s target multiple receptors, including GLP-1, the glucose-dependent insulinotropic polypeptide (GIP) and the glucagon receptor.
Over the 40-week trial, participants saw a 1.7 to 2 percent decrease in A1C—a measure of average blood sugar levels—while on retatrutide. And those who took the highest trial dose of 12 milligrams lost an average of 36.6 pounds over the study period, according to Eli Lilly.
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“Overall, this is incredibly exciting,” says Rozalina McCoy, an associate professor and endocrinologist at the University of Maryland, who was not involved in the trial. Retatrutide is the first “triple agonist” drug to be tested in this way, and it was unclear whether it would be any more effective than currently approved drugs.
While the data are still preliminary, McCoy says, they indicate that retatrutide has “greater efficacy” over a placebo for blood sugar and weight loss compared with previous trials of tirzepatide (which targets two receptors) and semaglutide. The results have yet to be published in full and have not yet been peer-reviewed, however.
“The retatrutide data are very solid,” says Daniel Drucker, a university professor of medicine at the University of Toronto, adding that the trial shows “excellent” weight-loss and A1C results. And the safety profile and discontinuation rates are “consistent” with other “established members of the broadening class of GLP-1 medicines, which is reassuring,” says Drucker, who has previously consulted for Eli Lilly but was also not involved in the trial.
The most common side effects among the trial group were nausea, diarrhea and vomiting. A small number of participants, between 2.3 and 4.5 percent, reported dysesthesia, a painful or burninglike sensation—a result that McCoy says researchers will need to study further to better understand.
Not every person who might be eligible for retatrutide will need to lose weight at such a fast rate—an average of nearly 37 pounds over 40 weeks—and such a rapid drop in A1C is also something that ought to be “watched” for additional side-effects, she says.
Ultimately, McCoy hopes retatrutide will soon add to “a growing tool kit” to tackle type 2 diabetes and obesity.
“We are in a new era that we have been waiting for—now the most important part is making sure that patients can access and use these medications safely, equitably and sustainably,” she says.