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

Structure Therapeutics reported on December 8, 2025 that aleniglipron, its once-daily oral GLP-1 pill, helped adults with obesity or excess weight lose weight in two mid-stage trials. In the main 36-week Phase 2b ACCESS study, the 120 mg dose produced 11.3% placebo-adjusted weight loss, and in the exploratory ACCESS II study the 240 mg dose reached 15.3% placebo-adjusted ^[1].

Aleniglipron is an investigational, orally available, once-daily, non-peptide small-molecule GLP-1 receptor agonist, the San Francisco-based company said ^[1]. It is not approved for patients, and the company said the results support moving it into a Phase 3 development program in mid-2026 ^[1].

The Phase 2b ACCESS results

ACCESS enrolled 230 adults with a body mass index of 30 or higher, or 27 or higher with at least one weight-related condition. Participants were assigned 3:1 to drug or placebo, started at 5 mg and followed a four-week titration to target doses of 45 mg, 90 mg or 120 mg once daily ^[1].

Average body weight change at 36 weeks was -9.0% at 45 mg, -10.7% at 90 mg and -12.1% at 120 mg, compared with -0.8% for placebo. The placebo-adjusted figures were -8.2%, -9.8% and -11.3%, all with p values below 0.0001 ^[1].

At the 120 mg dose, 86% of participants lost at least 5% of their body weight and 70% lost at least 10%. The study also reported drops in systolic blood pressure of 6.4 to 7.5 mmHg and HbA1c reductions of 0.28% to 0.37% ^[1].

Gastrointestinal side effects were the most common, with nausea and vomiting the two most frequent during the titration phase, and events generally appeared early in treatment. Between 7.7% and 13.3% of participants on active drug stopped treatment because of side effects, a mean of 10.4% across all active arms ^[1].

Higher doses in ACCESS II

ACCESS II enrolled 85 adults and tested 120 mg, 180 mg and 240 mg after the same four-week titration from 5 mg. The 44-week study is still running, and the 36-week figures come from a prespecified analysis ^[1].

At 36 weeks, average weight change was -13.1% at 120 mg, -13.3% at 180 mg and -14.2% at 240 mg, against +1.0% for placebo. Placebo-adjusted results were -14.1%, -14.4% and -15.3%, all with p values below 0.0001 ^[1]. Side effects were described as consistent with the GLP-1 drug class, with GI events most common and generally early ^[1].

The company also reported that no side-effect-related discontinuations were observed when participants started at a lower 2.5 mg dose in an open-label extension study and a body composition study ^[1].

"For the higher doses, the observed weight loss data at 36 weeks with no weight loss plateau is potentially best-in-class for oral small molecule GLP1s," said Raymond Stevens, Ph.D., the company's chief executive ^[1]. Julio Rosenstock, MD, chair of the ACCESS program steering committee, said the results are "very encouraging," and that the 15.3% figure "hopefully will be confirmed in larger, longer-term studies" ^[1].

Why it matters for patients

Every GLP-1 medication currently used for weight loss was given as an injection at the time of these results. Aleniglipron is designed as a once-daily pill, and that format is the main practical question here: whether a tablet can deliver weight loss in the same range as shots.

The company and outside groups argue an oral option could widen access. Joe Nadglowski, president and CEO of the Obesity Action Coalition, said "far too many individuals still face barriers to accessing effective, long-term treatment options" and that a once-daily oral therapy "has the potential to expand treatment options" ^[1]. Rosenstock said oral drugs of this type "have the potential to transform obesity treatment and broaden access" ^[1].

Several limits are worth keeping in mind. These are mid-stage results in 230 people (ACCESS) and 85 people (ACCESS II), not the larger, longer trials regulators usually require before approval. ACCESS II is ongoing and its 36-week numbers are a prespecified interim look ^[1]. Both studies compared the drug with placebo only; no head-to-head comparison with an approved weight-loss medicine has been reported. The 10.4% average discontinuation rate for side effects in ACCESS is also part of the picture, since stopping treatment limits how much weight a person can lose.

What happens next

Structure Therapeutics said it plans to advance aleniglipron into a Phase 3 clinical development program in mid-2026 ^[1]. ACCESS II continues toward its 44-week endpoint, and a 40-week body composition study using a 2.5 mg starting dose is ongoing ^[1].

No filing date with the Food and Drug Administration, no price and no launch timeline have been disclosed ^[1]. Aleniglipron remains investigational, so it is not available by prescription.