Oral Weight Loss Pill Helps Patients Lose up to 12% of Body Weight

An oral GLP-1 drug showed promising weight loss results in a phase II trial.

A pill-based approach to GLP-1 treatment helped adults with obesity or overweight lose as much as 12 percent of their body weight over 36 weeks, according to a randomized phase II clinical trial published in Nature Medicine.

The study tested aleniglipron, an oral small molecule GLP-1 drug now being developed as a possible obesity treatment. Robert Kushner, MD, ‘82 GME, professor emeritus of Medicine in the Division of Endocrinology, Metabolism and Molecular Medicine at Northwestern University, was a co-author of the study.

Oral delivery could expand access

Current GLP-1 drugs (glucagon-like peptide 1), including semaglutide products sold as Ozempic and Wegovy, have changed obesity and diabetes care, but most are peptide-based medications that must be injected. That delivery method can make treatment harder for some patients, and it also creates practical barriers involving refrigeration, manufacturing, cost, and supply.

GLP-1 drugs work by copying the effects of the body’s natural GLP-1 hormone. They stimulate insulin secretion, reduce appetite, and increase feelings of fullness, which can support weight loss.

Aleniglipron is different because it is designed as an oral medication. As a small molecule drug, it may be easier to manufacture at larger scale and could help address access and treatment gaps, 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.

Trial tested three doses

In the placebo-controlled, double blind trial, investigators studied the safety of aleniglipron in 230 adults with obesity or overweight. Participants had an average age of 50 years and were enrolled at 38 U.S. medical centers.

The adults were randomly assigned to one of three dose groups: 45, 90, or 120 milligrams. They took aleniglipron or a placebo once a day by mouth, with dose increases every four weeks over a total treatment period of 36 weeks.

Weight loss increased with dose

By week 36, weight loss was greater in each aleniglipron group than in the placebo group. Body weight fell by 9.0 percent from baseline in the 45 milligram group, 10.7 percent in the 90 milligram group, and 12.1 percent in the 120 milligram group, compared with 0.5 percent in the placebo group.

Gastrointestinal side effects were generally mild to moderate across patient groups and became less frequent over time. Across all groups, 10.4 percent of patients stopped treatment. No cases of drug-induced liver injury were reported.

Larger testing comes next

The results support continued development of aleniglipron as a potential obesity treatment, Kushner said. The medication’s effectiveness will be studied further in an upcoming phase III trial.

“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.

Reference: “Oral small molecule GLP-1 receptor agonist aleniglipron in people with overweight or obesity: a randomized, double-blind, placebo-controlled phase 2b trial” by Julio Rosenstock, Ildiko Lingvay, Donna Ryan, Ania M. Jastreboff, Robert Kushner, Andres Acosta, Thomas C. Blevins, Melissa Choi, Faith L. Holmes, Timothy Smith, Lisa Connery, Yao Li, Mike Ke Liu, Aline Barth, Jamie Butcher, Antonio Civitarese, Huibin Yue, Blai Coll and on behalf of the ACCESS Trial Investigators, 5 June 2026, Nature Medicine.
DOI: 10.1038/s41591-026-04476-6

This work was supported by Structure Therapeutics.

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