Mazdutide reduces body weight in adults with overweight or obesity: A high-dose Phase 1 trial.

This Phase 1 randomized, double-blind, placebo-controlled trial examined the safety and efficacy of mazdutide — a dual glucagon-like peptide-1 (GLP-1) and glucagon receptor agonist — at doses up to 16 mg in adults with overweight or obesity but without diabetes. Thirty-two participants received once-weekly subcutaneous injections of mazdutide (n=24, split across two dose-escalation cohorts) or placebo (n=8) for 20 weeks. The study found that both mazdutide cohorts experienced substantially greater mean percent reductions in body weight from baseline (approximately -20% and -21%, respectively) compared to the placebo group (approximately -0.1%), with statistically significant differences. The authors also reported improvements in metabolic markers and concluded that the 16 mg dose was well tolerated. Key limitations include the small sample size (particularly the placebo group of only 8 participants), the short 20-week duration, the Phase 1 design which is primarily safety-focused, and the absence of participants with diabetes, limiting generalizability. These findings suggest a dose-response relationship at higher doses than previously studied, but larger and longer trials are needed to confirm these results.

Why this grade: Although the study is a randomized, double-blind, placebo-controlled trial in humans, the very small sample size (n=32 total, n=8 placebo), short duration (20 weeks), and Phase 1 design limit the strength of evidence for efficacy conclusions.