Structure Therapeutics reports up to 15.3% weight loss for oral aleniglipron

Structure Therapeutics said on December 8, 2025 that its experimental once-daily pill aleniglipron produced placebo-adjusted mean weight loss of 11.3% (27.3 lbs) at the 120 mg dose after 36 weeks in a Phase 2b trial, and up to 15.3% (35.5 lbs) at a higher 240 mg dose in a separate exploratory study ^[1]. The company said the results support starting a Phase 3 program in mid-2026 ^[1].

Aleniglipron is an investigational oral, nonpeptide small molecule that activates the GLP-1 receptor ^[1]. That puts it in the same general category as other pills in development, rather than the injected peptide drugs semaglutide (Ozempic, Wegovy) or tirzepatide (Mounjaro, Zepbound). It is not approved by the FDA.

What the trials showed

The core Phase 2b ACCESS study enrolled 230 adults with obesity (BMI of 30 or higher) or overweight (BMI of 27 or higher) with at least one weight-related condition ^[1]. Participants were randomized 3:1 to drug or placebo, started at 5 mg, and titrated every four weeks to target doses of 45 mg, 90 mg or 120 mg once daily ^[1].

At 36 weeks, average weight change from baseline was −9.0% at 45 mg, −10.7% at 90 mg and −12.1% at 120 mg, compared with −0.8% on placebo ^[1]. Placebo-adjusted results were −8.2%, −9.8% and −11.3%, all with p<0.0001 ^[1]. In the 120 mg group, 86% of participants lost at least 5% of body weight and 70% lost at least 10% ^[1]. The company also reported drops in systolic blood pressure of 6.4 to 7.5 mmHg and in HbA1c of 0.28 to 0.37 percentage points ^[1].

The separate exploratory ACCESS II study enrolled 85 adults and tested target doses of 120 mg, 180 mg and 240 mg, again starting at 5 mg with four-week titration steps ^[1]. At 36 weeks, average weight change was −13.1%, −13.3% and −14.2%, while the placebo group gained 1.0% ^[1]. Because placebo participants gained weight, the placebo-adjusted figures were larger than the raw numbers: −14.1%, −14.4% and −15.3%, all p<0.0001 ^[1]. That 44-week study is still running; these are prespecified 36-week results ^[1].

Side effects and dropouts

Structure described a tolerability profile "consistent with the GLP-1 receptor agonist class" ^[1]. The most common side effects were gastrointestinal, with nausea and vomiting most frequent during titration, and adverse events generally showed up early in treatment ^[1].

In the core Phase 2b study, discontinuations because of adverse events ranged from 7.7% to 13.3% across doses, averaging 10.4% across all active arms ^[1]. The company also reported interim data from a body composition study of 71 adults that begins at a lower 2.5 mg starting dose and titrates monthly to 120 mg over 40 weeks; after a median follow-up of about 10 weeks, Structure said no adverse event-related discontinuations were seen with the 2.5 mg start, in that study and in an open-label extension ^[1]. The full interim data set was cut off in the available source text.

Why it matters for patients

A daily pill that does not require refrigeration or injection could, in principle, widen access. CEO Raymond Stevens said the higher-dose results showed "no weight loss plateau" at 36 weeks and called them "potentially best-in-class for oral small molecule GLP1s" ^[1]. Trial chair Julio Rosenstock, MD, was more measured, saying the up-to-15.3% result "hopefully will be confirmed in larger, longer-term studies" ^[1].

Those caveats matter. ACCESS II enrolled only 85 people, and the eye-catching 15.3% figure is placebo-adjusted, inflated in part because the placebo group gained weight ^[1]. Roughly one in ten participants in the core study stopped because of side effects ^[1]. And these are company-reported topline numbers, not peer-reviewed publications or FDA reviews.

The sources do not include head-to-head comparisons with semaglutide, tirzepatide, or orforglipron (Foundayo), and cross-trial comparisons are unreliable. Pricing, insurance coverage and long-term safety are not yet known.

What happens next

Structure said the data "comprehensively support and inform advancement to Phase 3 clinical development program in mid-2026" ^[1]. ACCESS II runs to 44 weeks and the body composition study to 40 weeks, so further readouts are expected ^[1]. A Phase 3 start in mid-2026 would still leave years of trials before any FDA filing.