Petrelintide, a long-acting amylin analogue, is in development for weight management. Early-phase randomized, double-blind, placebo-controlled trials published in Diabetes, Obesity and Metabolism evaluated the safety, tolerability, pharmacokinetics, and pharmacodynamics of petrelintide in single ascending dose (SAD) and multiple ascending dose (MAD) studies.

The SAD study examined subcutaneous doses ranging from 0.04 to 2.4 mg and one 0.35 mg intravenous dose. The MAD study included six once-weekly subcutaneous doses of 0.6 mg or 1.2 mg in part 1, followed by dose escalation every 2 weeks to target weekly doses of 2.4, 4.8, and 9.0 mg over 16 doses in part 2. Adults with overweight or obesity were enrolled in MAD part 2.

Across both trials, petrelintide was generally well tolerated, and no serious or severe treatment-emergent adverse events occurred. Gastrointestinal events were reported most often, although most were mild in intensity. One participant stopped treatment because of gastrointestinal adverse events. In MAD part 2, nausea was reported in 16.7% to 33.3% of participants receiving petrelintide compared with 16.7% with placebo. Diarrhea was uncommon, and vomiting was reported only in the participant who discontinued treatment.

Pharmacokinetic findings showed slow absorption, an approximate half-life of 10 days, and proportional exposure across dose levels at steady state. Body weight declined by as much as 8.6% after 16 weeks.

Petrelintide demonstrated favorable tolerability with meaningful weight reduction, supporting continued development as a weight-management therapy.