A new class of weight loss drugs just took a big step toward approval for use. In a phase 3 clinical trial, the drug 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 a new generation of weight loss drugs called GLP-3 agonists. While GLP-1 (glucagon-like peptide 1) agonist drugs such as semaglutide target a single hormone receptor that regulates hunger, GLP-3 targets multiple receptors, including GLP-1, the glucose-dependent insulinotropic polypeptide (GIP), and the glucagon receptor.
During the 40-week study, participants saw a 1.7 to 2 percent reduction 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 during the study period, according to Eli Lilly.
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“Overall, this is incredibly exciting,” says Rozalina McCoy, associate professor and endocrinologist at the University of Maryland. 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 effect” over a placebo for blood sugar and weight loss compared to earlier studies of tirzepatide (which targets two receptors) and semaglutide. The results have not yet been published in full and have not yet been peer-reviewed.
“The retatrutide data is very solid,” says Daniel Drucker, an associate professor of medicine at the University of Toronto, adding that the study shows “excellent” weight loss and A1C results. And the safety profile and discontinuation rate are “consistent” with other “established members of the expanded class of GLP-1 drugs,” he says, “which is reassuring.”
The most common side effects among the experimental group were nausea, diarrhea and vomiting. A small number of participants, between 2.3 and 4.5 percent, reported dysesthesia, a painful or burning sensation — a result that McCoy says researchers need to study further to better understand.
Not all people who may be eligible for retatrutide will need to lose weight at such a rapid rate — an average of nearly 37 pounds over 40 weeks — and such a rapid drop in A1C is also something that should be “monitored” for additional side effects, she says.
Ultimately, McCoy hopes that retatrutide will soon add to “a growing toolkit” for tackling type 2 diabetes and obesity.
“We are entering a new era that we have been waiting for – now the most important part is making sure that patients can access and use these medicines safely, fairly and sustainably,” she says.
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