What does this research mean for the field?

Once-daily oral aleniglipron significantly reduces body weight by up to 11.3% over 36 weeks in adults with overweight or obesity, while maintaining a tolerability profile typical of the GLP-1 receptor agonist class. Novelty: ClaimNovelty.NOVEL_FINDING. Consensus alignment: ConsensusAlignment.SUPPORTS_CONSENSUS.

What question did this study set out to answer?

To evaluate the efficacy and safety of aleniglipron in promoting weight loss among adults with obesity.

June 7, 2026Open Access

Oral small molecule GLP-1 receptor agonist aleniglipron in people with overweight or obesity: a randomized, double-blind, placebo-controlled phase 2b trial

Key Points

To evaluate the efficacy and safety of aleniglipron in promoting weight loss among adults with obesity.
Randomized, double-blind, placebo-controlled phase 2b trial involving 230 adults with a mean BMI of 39.5 kg/m².
Participants received aleniglipron doses of 45, 90, or 120 mg daily, escalated every 4 weeks.
Primary endpoint assessed body-weight change at week 36.
Participants in the 120 mg aleniglipron arm experienced an 11.3% weight loss (95% CI -13.9 to -8.6%, P < 0.0001 versus placebo).
Mild to moderate gastrointestinal events decreased over time, with no recurrence of vomiting noted.
Treatment discontinuations were 10.4% across aleniglipron arms, with no reports of liver injury.

Abstract

Abstract Aleniglipron is an oral, small-molecule glucagon-like peptide-1 receptor agonist (GLP1-RA) in development for obesity treatment. The ACCESS phase 2b placebo-controlled, double-blind study randomized 230 adults (mean BMI 39.5 kg m −2 , 54% female) with obesity or overweight to examine the effects of once-daily aleniglipron escalated every 4 weeks to 45, 90 or 120 mg. At week 36, the trial met its primary endpoint with a placebo-adjusted LS mean (95% confidence interval) body-weight change from baseline of −8.2% (−11.1 to −5.3%), −9.8% (−12.5 to −7.2%) and −11.3% (−13.9 to −8.6%) for the aleniglipron 45-, 90- and 120-mg arms, respectively ( P < 0.0001, all doses versus placebo), with no apparent weight-loss plateau at the end of the double-blind period. Continued weight loss was observed at the interim analysis (median treatment duration of 20 weeks) of the ongoing open-label extension. Gastrointestinal events were generally mild to moderate and decreased in frequency over time, with little to no recurrence of vomiting after reintroduction following permitted dose interruptions. Treatment-related discontinuations were 10.4% across aleniglipron arms, with no events of drug-induced liver injury. Clinically relevant weight reductions of up to 11.3% with a tolerability profile consistent with the GLP-1RA class support further development of aleniglipron for obesity treatment. ClinicalTrials.gov registration: NCT06693843 .

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