Structure Therapeutics publishes aleniglipron phase 2b obesity data in Nature Medicine

On June 5, 2026, Structure Therapeutics said results from its Phase 2b ACCESS trial of aleniglipron, an experimental once-daily oral GLP-1 receptor agonist, were published in Nature Medicine, describing weight loss that continued past 36 weeks and an overall discontinuation rate of 10.4% ^[1].

Aleniglipron is an oral small-molecule GLP-1 receptor agonist in development for obesity. It is not approved for sale. The paper, titled "Oral small molecule GLP-1 receptor agonist aleniglipron in people with overweight or obesity: a randomized, double-blind, placebo-controlled phase 2b trial," appeared alongside an oral presentation at the American Diabetes Association's 86th Scientific Sessions by Julio Rosenstock, MD, chair of the aleniglipron program steering committee and a clinical professor of medicine at the University of Texas Southwestern Medical Center ^[1].

At Week 36, each of the three maintenance doses tested in the core study reached statistical significance on the primary endpoint and on all key secondary endpoints, the company said. The June 5 announcement does not restate the Week 36 weight-loss percentages, describing them as previously reported. It does say other cardiovascular risk measures improved with aleniglipron, including systolic and diastolic blood pressure, hsCRP, waist circumference and HbA1c ^[1].

In a predefined interim analysis of the open-label extension safety study, participants continued to lose weight after a median of 20 additional weeks of follow-up, with no apparent weight-loss plateau. Weight loss reached 13.3%, 16.2% and 15.3% among participants who came from the 45 mg, 90 mg and 120 mg arms of the double-blind period, respectively ^[1].

Adverse events looked like those seen with other GLP-1 medicines. Gastrointestinal events were generally mild to moderate and became less frequent over time, and most discontinuations occurred during the initial dose titrations. The company reported no clear dose-response relationship for the most common GI events across treatment arms, and said discontinuations due to any treatment-related adverse event were limited ^[1]. It also reported that when participants interrupted or reduced dosing and later restarted or moved to a higher dose, vomiting rarely recurred — a pattern the company says may help patients stay on treatment longer ^[1].

"Interestingly, participants continued to lose weight after a median follow up of 20 weeks in the open label extension phase of the study after finalizing the 36 weeks in the double-blind treatment period, with no apparent weight loss plateau," Rosenstock said in the release, calling that "an important distinction for a once-daily oral, non-peptide GLP-1 receptor agonist to potentially become an additional treatment option for patients" ^[1].

Why it matters for patients

Aleniglipron is still experimental, and the announcement gives no timeline for regulatory approval or a filing. If it eventually reaches the market, it would be taken as a once-daily pill rather than an injection ^[1].

How long people stay on an obesity drug shapes how much benefit they can get, and GI side effects are the leading reason patients stop GLP-1 treatment in general. The 10.4% overall discontinuation rate reported here comes from a company-sponsored trial, and the release does not compare it with approved products. The release also does not say how the trial's participants compared with the broader US patient population, or whether the open-label extension results — where participants know they are receiving the drug — will hold up in a larger, blinded Phase 3 study. That has not been established.

What happens next

Structure Therapeutics says its Phase 3 program for aleniglipron remains on track to begin in the third quarter of 2026, using a 2.5 mg starting dose and evaluating multiple doses based on the Phase 2b data and an end-of-Phase 2 meeting with the FDA, according to chief medical officer Blai Coll, MD, PhD ^[1].

At the same ADA meeting, the company plans additional presentations on its obesity pipeline: a late-breaking poster on a lower starting dose and GI tolerability, and a late-breaking poster on aleniglipron combined with a small-molecule amylin receptor agonist, ACCG-2671, both on June 7 from 12:30 to 1:30 p.m. CT. A June 8 poster covering the Phase 2 ACCESS II trial, which tested aleniglipron at doses up to 240 mg, runs at the same time ^[1].