Summary: In adults aged 18 to 55 years with overweight or obesity, this phase 1b/2a, placebo-controlled trial (n=125; amycretin n=101, placebo n=24) was designed primarily to assess the safety and tolerability of once-weekly subcutaneous amycretin, a unimolecular GLP-1 and amylin receptor agonist. Treatment-emergent adverse events were mostly mild-to-moderate gastrointestinal events. Bodyweight change, a secondary endpoint, favoured amycretin across doses, reaching a mean of minus 24.3 percent versus minus 1.1 percent for placebo at the 60 mg maintenance dose by week 36 (p<0.0001).
PICO Summary
| Element | Detail |
|---|---|
| Population | 125 adults aged 18 to 55 years with overweight or obesity (BMI 27.0 to 39.9 kg/m2); randomised, double-blind, single-centre study (San Antonio, USA). |
| Intervention | Once-weekly subcutaneous amycretin (GLP-1 and amylin receptor agonist), dose-escalated to maintenance doses of 1.25, 5, 20, or 60 mg over 20 to 36 weeks (n=101). |
| Comparison | Matching subcutaneous placebo over the same treatment durations (n=24). |
| Outcome | Primary endpoint was treatment-emergent adverse events; most were mild-to-moderate gastrointestinal events. Mean bodyweight change (secondary endpoint) versus placebo: 60 mg minus 24.3 percent vs minus 1.1 percent (week 36); 20 mg minus 22.0 percent vs plus 1.9 percent (week 36); 5 mg minus 16.2 percent vs plus 2.3 percent (week 28); 1.25 mg minus 9.7 percent vs plus 2.0 percent (week 20). Between-group differences were significant (Parts A to D p<0.0001; Part E p=0.0003). Withdrawals were frequent, mostly for reasons unrelated to adverse events. No 95 percent confidence intervals, absolute risk reduction, or number needed to treat were reported for the weight outcome. |
Amycretin for weight loss
Phase 1b/2a RCT · overweight/obesity · 36 weeks
At the 60 mg dose, amycretin cut mean bodyweight by 24.3 percent versus 1.1 percent for placebo by week 36. Weight was a secondary, exploratory endpoint in a small single-centre safety trial, so the effect needs phase 3 confirmation.
Expert Commentary
This is an early-phase study, and its purpose was to establish safety, tolerability, and pharmacokinetics rather than to prove efficacy. On that primary question the verdict is reassuring: the tolerability profile of once-weekly subcutaneous amycretin was consistent with what is expected of GLP-1 and amylin agonists, with gastrointestinal events predominating and most being mild to moderate. The headline weight-loss figures are striking, with mean reductions reaching roughly a quarter of bodyweight at the highest dose, but they are secondary, exploratory findings and should be read with caution. The most important limitation is the design itself: a small, single-centre study with only 24 placebo participants, substantial dropout, dose arms of differing length, and no confidence intervals reported for the weight effect, all of which inflate uncertainty around such large point estimates. The trial was funded by the manufacturer, and these magnitudes are implausibly strong for definitive interpretation at this stage. Can I use this with my patients? Not yet; amycretin is investigational and unavailable for clinical use, and these data cannot guide prescribing. The appropriate next step is adequately powered, multicentre phase 3 trials with durability and cardiometabolic outcomes before any conclusion about real-world benefit is warranted.
References
Dahl K, Toubro S, Dey S, Duque do Vale R, Flint A, Gasiorek A, et al. Amycretin, a novel, unimolecular GLP-1 and amylin receptor agonist administered subcutaneously: results from a phase 1b/2a randomised controlled study. Lancet. 2025;406(10499):149-162. doi:10.1016/S0140-6736(25)01185-7