Structure Therapeutics publishes aleniglipron Phase 2b data in Nature Medicine

Structure Therapeutics has published full results from its Phase 2b ACCESS trial of aleniglipron, an experimental once-daily oral GLP-1 receptor agonist for obesity, in the journal Nature Medicine ^[1]. The paper appeared alongside a presentation at the American Diabetes Association's 86th Scientific Sessions, given by lead investigator Dr. Julio Rosenstock of UT Southwestern Medical Center ^[1].

The headline safety number is a 10.4% overall discontinuation rate across the trial, which the company describes as favorable for a GLP-1 medicine ^[1]. Gastrointestinal side effects were generally mild to moderate and became less frequent over time, and most people who stopped taking the drug did so during the early dose-increase period rather than later ^[1]. Notably, the company reports that when participants had their dose paused or lowered because of side effects and then restarted or increased it again, vomiting rarely came back ^[1].

At the 36-week mark, all three maintenance doses tested in the core study — 45 mg, 90 mg and 120 mg — met the trial's main weight-loss goal and all secondary goals with statistical significance ^[1]. People also saw improvements in systolic and diastolic blood pressure, a marker of inflammation called hsCRP, waist size, and blood sugar (HbA1c) ^[1]. In an open-label extension that followed patients for a median of 20 more weeks after the 36-week mark, weight loss continued without an apparent plateau, reaching 13.3% for the 45 mg group, 16.2% for the 90 mg group, and 15.3% for the 120 mg group ^[1].

Based on this data and an end-of-Phase 2 meeting with the FDA, Structure says its Phase 3 program will start participants on a lower 2.5 mg dose and test multiple dose levels, with the trial expected to begin in the third quarter of 2026 ^[1].

Why it matters for patients

Aleniglipron is a pill, not an injection, which could matter for people who prefer not to inject themselves or who have trouble accessing injectable GLP-1 drugs like Ozempic, Wegovy, or Zepbound. The reported 10.4% discontinuation rate is one data point suggesting people may be able to stay on this drug for longer stretches, though it comes from a mid-stage trial, not the larger Phase 3 studies that will more directly compare it to real-world use ^[1].

The finding that weight loss kept going past 36 weeks, without leveling off through the extension period, is also notable because plateauing weight loss is a common pattern with existing GLP-1 medicines. Whether that pattern holds up in a larger, longer Phase 3 trial is not yet known.

The detail about vomiting rarely recurring after a dose pause or restart could be relevant for people who need to interrupt treatment for any reason, since it suggests the tolerability problem may not simply return each time the dose changes. Still, this comes from one trial's data and has not been confirmed in later-stage research.

What happens next

Structure Therapeutics said it plans to start its Phase 3 program for aleniglipron in the third quarter of 2026, using a 2.5 mg starting dose and testing multiple dose levels ^[1]. The company also has additional data on its obesity pipeline, including a separate poster on a lower starting dose for tolerability and posters on combining aleniglipron with an experimental amylin drug, scheduled for presentation at the ADA meeting on June 7 and June 8, 2026 ^[1]. Results from the full Phase 3 program, which will determine whether these Phase 2b findings hold up in a larger population, are not yet available.