Phase 1 trial of once-weekly eloralintide shows weight reduction in obesity over 12 weeks

This Phase 1, randomised, placebo-controlled trial evaluated the safety, tolerability, pharmacokinetics, and pharmacodynamics of once-weekly subcutaneous eloralintide (LY3841136), a selective amylin receptor agonist, in 100 participants with obesity or overweight. The study was conducted at three centres in the United States. Participants had a mean age of 44 years, 29% were female, and the mean body mass index was 32.6 kg/m². The intervention involved five multiple ascending dose cohorts of eloralintide without dose escalation, compared against placebo, over a 12-week follow-up period.

The main finding was a dose-proportional pharmacokinetic profile. For body weight, the least squares mean percent reduction across the dose groups ranged from 2.6% to 11.3% at 12 weeks. No p-values, confidence intervals, or absolute numbers for weight loss were reported. The most common treatment-emergent adverse events with eloralintide were decreased appetite (19% of participants), headache (12%), fatigue (11%), and COVID-19 (11%). Gastrointestinal events included diarrhoea (10%), nausea (8%), and vomiting (4%). Most adverse events were mild in severity. One serious adverse event occurred in the 6 mg cohort and was deemed unrelated to the study drug. Discontinuation rates were not reported.

Key limitations stem from the study's early-phase nature. This was a proof-of-concept study with a small sample size of 100 participants and a short 12-week duration. The absence of reported p-values or confidence intervals for the weight loss results limits statistical interpretation. The practice relevance is not established, as this Phase 1 trial primarily assesses safety and pharmacokinetics. Efficacy and long-term safety require confirmation in larger, Phase 2/3 trials.