Mazdutide

This randomized, double-blind, placebo-controlled phase 2 trial enrolled 248 Chinese adults with overweight (BMI ≥24 kg/m² with hyperphagia or at least one obesity-related comorbidity) or obesity (BMI ≥28 kg/m²) across 20 hospitals. Participants were randomized to once-weekly subcutaneous mazdutide 3 mg, 4.5 mg, 6 mg, or matching placebo for 24 weeks. Mean percentage change in body weight from baseline at week 24 was -6.7%, -10.4%, and -11.3% for the 3 mg, 4.5 mg, and 6 mg arms respectively, versus +1.0% for placebo. Secondary endpoints — including the proportion of participants achieving ≥5%, ≥10%, and ≥15% weight reduction, and improvements in waist circumference, blood pressure, lipid profile, and liver enzymes — favored mazdutide across the dose range. The adverse-event profile was predominantly gastrointestinal and dose-dependent, consistent with the incretin and glucagon agonist class.

Researchers ran a 24-week study in roughly 250 Chinese adults with overweight or obesity, comparing three doses of weekly mazdutide injections (3 mg, 4.5 mg, 6 mg) to placebo. Average weight loss climbed with dose — about 7%, 10%, and 11% at the three dose levels — while placebo participants gained a small amount of weight on average. Most side effects were stomach-related (nausea, decreased appetite, diarrhea), as is typical for this class of molecule.

This multiple-ascending-dose phase 1b trial evaluated higher dose levels of mazdutide (9 mg and 10 mg once weekly) over 16 weeks in Chinese adults with overweight or obesity. Participants in the active arms demonstrated dose-dependent reductions in body weight, waist circumference, fasting plasma glucose, and serum lipids relative to placebo, with the higher dose cohorts achieving mean placebo-adjusted weight reductions exceeding those reported at the 6 mg dose ceiling tested in the earlier phase 1b dose range. Pharmacokinetic data supported once-weekly dosing. Gastrointestinal events were the most common adverse events and were generally mild to moderate, with no new safety signals identified compared with lower doses. The authors concluded the data supported continued investigation of higher mazdutide doses in adults with obesity.

A smaller, earlier-stage study tested higher mazdutide doses (9 mg and 10 mg weekly) in Chinese adults with overweight or obesity over 16 weeks. The higher doses produced larger reductions in body weight and improvements in blood-sugar and lipid markers than the lower doses tested earlier. Side effects were mostly mild stomach symptoms, similar in nature to those seen at lower doses. The findings supported moving forward with higher-dose studies.