Lau DCW, Erichsen L, Satylganova A, et al. - Findings demonstrate good tolerability of cagrilintide (a long-acting amylin analogue) as well as significant decreases in bodyweight after its administration in individuals with overweight and obesity. The development of molecules with novel mechanisms of action for weight management is supported by the observations.

• In this multicenter, randomized, double-blind, placebo-controlled and active-controlled, dose-finding phase 2 trial, a total of 706 adults aged at least 18 years without diabetes, with a BMI of at least 30 kg/m ² or at least 27 kg/m ² with hypertension or dyslipidemia were randomized to cagrilintide 0·3–4·5 mg (100–102 per dose group), 99 to liraglutide 3·0 mg, and 101 to placebo.

• Greater mean percentage weight reductions, from baseline to week 26, were achieved with all doses of cagrilintide (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).

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

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

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