Lau DCW, Erichsen L, Francisco AM, et al. - Findings demonstrate good tolerability as well as effectiveness of cagrilintide (a long-acting amylin analogue) in significantly decreasing bodyweight in people with overweight and obesity. The development of molecules with novel mechanisms of action for weight management is backed.

• In this multicenter, randomized, double-blind, placebo-controlled and active-controlled, dose-finding phase 2 trial, adults aged at least 18 years without diabetes, with a body-mass index of at least 30 kg/m ² or at least 27 kg/m ² with hypertension or dyslipidemia were included.

• Participants were randomized (6:1) to subcutaneous self-injections of once-weekly cagrilintide (0·3, 0·6, 1·2, 2·4, or 4·5 mg) (n=706), once-daily liraglutide 3·0 mg (n=99), or volume-matched placebo (n=101) (for six placebo groups).

• All doses of cagrilintide provided greater mean percentage weight reductions from baseline to week 26 (0·3–4·5 mg, 6·0%–10·8% [6·4–11·5 kg]) vs placebo (3·0% [3·3 kg]; estimated treatment difference range 3·0%–7·8%; p<0·001), according to the trial product estimand (assuming all participants were adherent to treatment).

• Cagrilintide 4·5 mg offered greater weight reductions vs liraglutide 3·0 mg (10·8% [11·5 kg] vs 9·0% [9·6 kg]; estimated treatment difference 1·8%, p=0·03).

• Similar weight loss decreases were noted with the treatment policy estimand (irrespective of adherence to treatment).

• Gastrointestinal adverse events occurred in more participants taking cagrilintide 0·3–4·5 mg vs placebo (41%–63% vs 32%), primarily nausea (20%–47% vs 18%).