Efficacy and safety of mazdutide in adults with obesity or overweight: a US-based, multicentre, phase 2, randomised, placebo-controlled clinical trial.

Once-weekly subcutaneous mazdutide in US adults with obesity or overweight produced least-squares bodyweight reductions at 32 weeks, reaching -18·1% with 16 mg versus -0·9% with placebo.

• Why it matters: Weight-loss drugs that target GLP-1 and GIP pathways have shown benefit, but differentiated options are needed to improve efficacy and understand dose-related safety in adults without type 2 diabetes.
• What they did: In a US multicentre phase 2 randomized, double-blind, placebo-controlled trial (24 centres), adults without type 2 diabetes received placebo or mazdutide 3–6 mg, 10 mg, or 16 mg once weekly for 48 weeks; the primary endpoint was bodyweight change at 32 weeks.
• The result: At 32 weeks, treatment differences versus placebo ranged from -6·5% to -17·2% (p<0·0001), with additional reductions at 48 weeks; gastrointestinal adverse events were most common, and discontinuation due to adverse events was highest with 16 mg (20%).

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