Enebo LB, Berthelsen KK, Kankam M, et al. - Because cagrilintide, a long-acting amylin analogue, and semaglutide 2·4 mg, a glucagon-like peptide-1 analogue, are both being studied as weight-management options, researchers conducted this randomised, placebo-controlled, multiple-ascending dose, phase 1b trial to determine the safety, tolerability, pharmacokinetics, and pharmacodynamics of this drug combination. Individuals between the ages of 18 and 55 with a BMI of 27·0−39·9 kg/m ² and who were otherwise healthy were selected from a single centre in the USA. The trial involved six sequential overlapping cohorts, and in each cohort eligible candidates were randomly assigned (3:1) to once-weekly subcutaneous cagrilintide (0·16, 0·30, 0·60, 1·2, 2·4, or 4·5 mg) or matched placebo, in combination with once-weekly subcutaneous semaglutide 2·4 mg, without lifestyle interventions. Between July 25, 2018, and December 17, 2019, 285 people were screened and 96 were randomly assigned to cagrilintide (0·16–2·4 mg group n = 12; 4·5 mg group n = 11) or placebo (n = 24), in combination with semaglutide 2·4 mg, of whom 95 were exposed to treatment (one patient in 0·60 mg cagrilintide group was not exposed) and involved in the safety and full analysis datasets. The combination of cagrilintide and semaglutide 2·4 mg was well tolerated and had an acceptable safety profile. Future larger and longer trials are required to fully evaluate the effectiveness and safety of this treatment combination.