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June 2026 NEW GLP-1 DRUG PROMOTES WEIGHT LOSS IN OBESITYFeaturing: Robert Kushner, MD, ‘82 GME
A new strategy for delivering GLP-1 drugs to patients with obesity or who were overweight resulted in up to a 12 percent reduction in body weight after 36 weeks, according to a randomized phase II clinical trial published in Nature Medicine. Robert Kushner, MD, ‘82 GME, professor emeritus of Medicine in the Division of Endocrinology, Metabolism and Molecular Medicine, was a co-author of the study. Unlike currently available GLP-1 drugs (glucagon-like peptide 1) including semaglutide, sold as Ozempic and Wegovy, aleniglipron is a small-molecule drug that is taken orally and is currently in development for the treatment of obesity. All GLP-1 drugs mimic the effects of the naturally occurring GLP-1 hormone, stimulating insulin secretion, suppressing appetite and increasing satiety to promote weight loss. Despite their effectiveness, currently available peptide-based GLP-1 drugs are not widely accessible; those medications must be injected, which limits patient access due to how the medication is administered, as well as present challenges with storing the medication (refrigeration) and scalability issues due to manufacturing and cost. In contrast, small-molecule GLP-1 drugs can be taken orally and manufactured on a larger scale, addressing gaps in both accessibility and treatment outcomes, Kushner said. “The difference with aleniglipron is it’s a small molecule, which means it’s chemically made and could be taken with or without food. Most medications we take, whether it’s aspirin or blood pressure medicine, are small molecules. They’re chemicals that you make structurally, and because of that you can potentially combine them with other medications,” Kushner said. In the current placebo-controlled, double-blind clinical trial, the investigators evaluated the safety of aleniglipron in 230 adults (average age of 50 years) with obesity or overweight at 38 U.S. medical centers. Participants were randomized to three dose-level cohorts: 45, 90 or 120 milligrams. Participants were instructed to take once-daily aleniglipron orally and then increase their dose every four weeks with aleniglipron or placebo for a total of 36 weeks. At week 36, body-weight change from baseline was −9.0 percent in the 45 milligrams group, -10.7 percent in the 90 milligrams group and –12.1 percent in the 120 milligrams group compared to -0.5 percent for the placebo group. Gastrointestinal side effects were mild to moderate across all patient groups and decreased in frequency over time. Across all groups, 10.4 percent of patients discontinued treatment and no events of drug-induced liver injury were reported. The findings support the development of alenglipron for the treatment of obesity and further testing of the medication’s efficacy in an upcoming phase III trial, Kushner said. “We didn’t find any concerns; no new safety signals. We found a dose that seems to be effective, and the dose escalation will be slowed down further as we go into phase III trial to increase tolerability,” Kushner said. This work was supported by Structure Therapeutics. This article was originally published in the Feinberg School of Medicine News Center on June 24, 2026. |
Robert Kushner, MD, ‘82 GME, professor emeritus of Medicine in the Division of Endocrinology, Metabolism and Molecular Medicine, was a co-author of the study.
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