Phase 2 trial reports dose-related weight loss with mazdutide in U.S. adults

A U.S. phase 2 trial found greater average weight loss with higher doses of mazdutide, an investigational medicine that activates GLP-1 and glucagon receptors. The randomized, double-blind trial enrolled 179 adults with obesity or overweight and at least one weight-related condition. None had type 2 diabetes.

The 48-week study ran at 24 U.S. centers. Weekly injections were assigned as placebo, a lower-dose mazdutide schedule that increased from 3 mg to 6 mg, a 10 mg dose, or a 16 mg dose. Researchers based the primary result on relative body-weight change through the first 32 weeks.

By that assessment, the adjusted mean reductions were 7.3% in the lower-dose group, 15.6% at 10 mg, and 18.1% at 16 mg. The corresponding placebo result was a 0.9% reduction. After subtracting the placebo change, the smallest treatment effect was 6.5 percentage points and the largest was 17.2. Each comparison met the trial's statistical threshold.

The paper reported further average weight reduction through week 48. Gastrointestinal problems were the most common adverse events and were generally described as mild or moderate. Discontinuation because of adverse events was most frequent in the 16 mg group, where it affected 20% of participants and was mainly related to gastrointestinal disorders.

Dose selection balances efficacy and discontinuation

The trial provides randomized U.S. evidence across several mazdutide doses. The results show an efficacy signal and a clear reason to study dose selection carefully. The highest dose produced the largest mean loss at week 32, but it also had the highest treatment-discontinuation rate.

The 3-to-6 mg group followed a different schedule from the fixed-dose groups. Participants stayed at 3 mg through week 32 and then increased to 6 mg, allowing investigators to explore the lower doses as possible maintenance options.

Phase 2 results do not rank approved treatments

This phase 2 study does not establish long-term effectiveness, long-term safety, or how mazdutide compares directly with approved obesity medicines. It was not designed as a head-to-head trial against semaglutide or tirzepatide.

The results are group averages from 179 participants and cannot predict an individual's response. People with type 2 diabetes were not included, and the 48-week study cannot answer questions about outcomes after years of treatment.

Mazdutide remains investigational in the United States. The trial was funded by Eli Lilly, and several authors reported employment and stock ownership in the company. Those disclosures do not invalidate the findings, but they belong in the evidence record when the study is interpreted.