Oral GLP-1 pill aleniglipron reaches up to 11.3% placebo-adjusted weight loss in a phase 2b trial

In the 230-person ACCESS dose-finding study, the investigational once-daily pill — not approved or available for prescription — met its primary endpoint at all three doses, with weight loss not yet plateaued at 36 weeks; the trial excluded people with diabetes and enrolled overweight participants only with a weight-related comorbidity.

The race to deliver a GLP-1 obesity drug as a pill rather than a syringe gained a credible new entrant this week. In the phase 2b ACCESS trial, the oral small-molecule GLP-1 receptor agonist aleniglipron (GSBR-1290) met its primary endpoint, producing placebo-adjusted weight loss of up to 11.3% at 36 weeks, according to results published in Nature Medicine on 5 June 2026. Aleniglipron is investigational: it is not approved by any regulator and is not available for prescription.

A note on who was studied. Per the trial registry, ACCESS excluded anyone with a previous documented diagnosis of diabetes mellitus and enrolled overweight participants (BMI ≥27) only if they had at least one weight-related comorbidity. The results therefore should not be assumed to generalize to people with diabetes, or to overweight people without a weight-related comorbidity.

ACCESS randomized 230 adults with obesity or overweight — mean body-mass index 39.5 kg/m², 54% female — to once-daily aleniglipron, escalated every four weeks to 45, 90 or 120 mg, or to placebo, in a double-blind design. Per ClinicalTrials.gov, the study (NCT06693843), sponsored by Gasherbrum Bio, a subsidiary of Structure Therapeutics, ran across 39 US sites and is now active but not recruiting, with an open-label extension underway.

The primary endpoint was percent change in body weight from baseline to week 36. At that point, the placebo-adjusted least-squares mean body-weight change was −8.2% (95% CI −11.1 to −5.3) for 45 mg, −9.8% (−12.5 to −7.2) for 90 mg and −11.3% (−13.9 to −8.6) for 120 mg, all significant at P < 0.0001 versus placebo. The authors reported no apparent weight-loss plateau by the end of the 36-week double-blind period — an interim observation from a dose-finding trial, not a durability finding — and continued weight loss at an interim analysis of the open-label extension (median treatment duration 20 weeks).

“Clinically relevant weight reductions of up to 11.3% with a tolerability profile consistent with the GLP-1RA class support further development.”

How it compares

On safety, the authors reported that gastrointestinal events among aleniglipron-treated participants were generally mild to moderate and decreased over time, with little to no recurrence of vomiting after dose reintroduction following permitted interruptions. Treatment-related discontinuations reached 10.4% across the aleniglipron arms, and the authors recorded no events of drug-induced liver injury in aleniglipron-treated participants — a point of interest given liver-signal concerns that have dogged some oral small-molecule candidates in this class.

Two caveats temper the readout. This is a 36-week, dose-finding phase 2b trial, not a confirmatory phase 3, and the headline figures are placebo-adjusted, not absolute. The deeper responder-rate breakdowns and head-to-head positioning against injectable semaglutide or tirzepatide, and against oral rivals such as orforglipron, await larger and longer trials. For now, ACCESS establishes that a small-molecule pill can reach double-digit weight loss over 36 weeks without an early plateau in this dose-finding population.

Trials Today

Phase 3 EPIK-O (alpelisib + olaparib vs chemotherapy, platinum-resistant ovarian cancer) — Terminated; results posted. Primary PFS negative — median 3.6 vs 3.9 mo, HR 1.142 (95% CI 0.882-1.478). n=358.

Phase 3 LIBREXIA-ACS (milvexian, oral Factor XIa inhibitor, post-ACS) — Status updated to Completed (primary completion 2026-02-06); n=14,194. No efficacy/safety results posted yet — readout pending.

Phase 3 VALOR (VLA15 6-valent OspA Lyme disease vaccine, Pfizer/Valneva) — Status updated to Completed (primary completion 2026-01-07); n=12,546, age 5+. No efficacy results posted yet.

At the Agencies

Salanersen (Biogen) — FDA Breakthrough Therapy Designation, spinal muscular atrophy — Granted June 4, 2026. Once-yearly intrathecal antisense oligonucleotide. Designation only — not a filing acceptance or approval.

Etcamah (camizestrant, AstraZeneca) — CHMP positive opinion, ESR1-mutant HR+/HER2- breast cancer — Among 8 new-medicine positive opinions at the May 18-21, 2026 CHMP meeting; one refusal (Deqtynet). CHMP recommendation, not final EC approval.