This page is educational and non-prescriptive. Mazdutide is not approved by the US FDA; this page summarizes published trial evidence and does not recommend any use of it.
Evidence status
Mazdutide is unusual among the newer incretin agents in this catalog: it has completed phase 3 trials, and those trials are published in The New England Journal of Medicine and JAMA. This is clinical-stage evidence of the highest available tier—randomized, double-blind, placebo-controlled, with hundreds of participants and pre-specified coprimary endpoints.
The single most important qualifier is geographic. Every pivotal trial to date enrolled Chinese adults at Chinese sites, so the efficacy and safety estimates describe that population. Mazdutide has been reviewed for weight management in China; it holds no FDA approval, and regulatory status differs by jurisdiction.
The dual-agonist rationale
Mazdutide (also identified as IBI362 and LY3305677) is an oxyntomodulin analogue acting as a dual agonist at the GLP-1 receptor and the glucagon receptor. The GLP-1 arm drives the appetite suppression and glucose lowering familiar from semaglutide-class drugs. The glucagon arm is the differentiator: glucagon receptor agonism is hypothesized to raise energy expenditure and reduce hepatic fat, adding an output-side effect to an intake-side one.
Balancing the two is the central pharmacological problem, since glucagon agonism alone would raise blood glucose. The trials below are what determine whether the balance works in practice.
The phase 3 trials
| Trial | Design | n | Dose | Duration | Mean weight change |
|---|---|---|---|---|---|
| GLORY-1 | Phase 3, double-blind, placebo-controlled | 610 | 4 mg or 6 mg weekly | 48 weeks | −11.00% (4 mg), −14.01% (6 mg) vs +0.30% placebo |
| GLORY-2 | Phase 3, double-blind, placebo-controlled, 27 sites | 461 | 9 mg weekly | 60 weeks | −16.65% vs −1.50% placebo |
GLORY-1 (NEJM 2025; PMID 40421736) randomized adults aged 18–75 with a BMI of at least 28, or 24 to under 28 with a weight-related condition, 1:1:1 to 4 mg mazdutide, 6 mg, or placebo. Mean baseline weight was 87.2 kg and mean BMI 31.1. At week 32, weight change was −10.09% (4 mg), −12.55% (6 mg), and +0.45% (placebo), with at least 5% weight reduction in 73.9%, 82.0%, and 10.5% respectively (p<0.001 for all comparisons). At week 48 the figures reached −11.00%, −14.01%, and +0.30%.
GLORY-2 (JAMA 2026; PMID 42251595) tested a higher 9 mg dose across 27 hospitals from December 2023 to November 2025 in adults with a BMI of at least 30, randomized 2:1 to mazdutide (n=308) or placebo (n=154), for 60 weeks. Participants were 64.0% female, 16.1% with type 2 diabetes, mean age 33.9 years, mean weight 94.0 kg, mean BMI 34.3. At week 60, mean weight change was −16.65% versus −1.50% on placebo (between-group difference −15.15%, 95% CI −17.22 to −13.09, p<0.001), and 84.3% versus 33.1% achieved at least 5% reduction.
Both trials used treatment-policy estimands, meaning the results count participants regardless of early discontinuation or starting other anti-obesity therapy—a conservative analysis choice that makes the effect estimates harder to inflate.
Diabetes trials
Mazdutide has also been evaluated in type 2 diabetes, with phase 3 results published in Nature in 2026 comparing it against placebo (PMID 41407859) and against the GLP-1 receptor agonist dulaglutide (PMID 41407860). The active-comparator design in the second is the more informative one, since beating placebo and beating an established drug are different bars. Both were conducted in Chinese adults.
What the data does not cover
- Population. The pivotal trials enrolled Chinese adults exclusively. Body composition, baseline BMI distribution, and diabetes prevalence differ across populations, so effect sizes may not transfer directly.
- Duration. The longest published trial ran 60 weeks. Obesity pharmacotherapy is generally long-term, and weight regain after discontinuation is a well-documented feature of this drug class that these trials were not designed to characterize.
- Cardiovascular outcomes. No completed outcome trial establishes whether mazdutide reduces cardiovascular events, as has been shown for some GLP-1 agonists.
- Comparative positioning. No published head-to-head trial against semaglutide or tirzepatide, so cross-trial percentage comparisons—which differ in population, duration, and estimand—are unreliable.
Approval in one jurisdiction is not approval elsewhere, and the material sold as "mazdutide" outside a pharmacy supply chain is not the manufactured product these trials evaluated.