Mazdutide
IBI362, LY3305677, OXM-3
Mazdutide is a once-weekly dual agonist at the GLP-1 and glucagon receptors, engineered from human oxyntomodulin. It was approved by China's National Medical Products Administration in 2025 for chronic weight management and for glycaemic control in type 2 diabetes, making it the first Chinese-developed GLP-1 and glucagon receptor dual agonist to complete phase 3 registration trials. It remains investigational elsewhere.
Mechanism
Mazdutide is derived from oxyntomodulin, a 37-residue peptide produced from the same proglucagon precursor as GLP-1 and glucagon, and which in its native form is itself a weak agonist at both the GLP-1 and glucagon receptors. Native oxyntomodulin is degraded within minutes by dipeptidyl peptidase-4 and cleared rapidly, so it is useless therapeutically. Mazdutide retains the dual-receptor character while adding residue substitutions for protease resistance and a fatty diacid side chain that binds circulating albumin reversibly, extending exposure to a weekly interval. Reported binding affinities at the two human receptors are of broadly similar order of magnitude, giving a genuinely balanced rather than heavily GLP-1-weighted profile.
The functional consequence is the same two-armed pharmacology as other glucagon-containing multi-agonists. GLP-1 receptor activation reduces appetite, slows gastric emptying and enhances glucose-dependent insulin secretion; glucagon receptor activation increases resting energy expenditure and hepatic fatty acid oxidation, reduces hepatic steatosis and mobilises lipid stores. Mazdutide's development programme has emphasised effects beyond weight, including reductions in liver fat, serum uric acid, blood pressure and lipids, several of which are plausibly attributable to the glucagon component rather than to weight loss alone, though that attribution has not been formally demonstrated.
What the research shows
The phase 1b and phase 2 work in Chinese adults established dose-dependent reductions in body weight and HbA1c and defined the 4 mg and 6 mg weekly doses taken into registration trials. The phase 1b study was small, at 43 patients over 12 weeks across nine centres, and included a dulaglutide reference arm. The phase 2 obesity trial randomised 248 participants across 20 Chinese hospitals over 24 weeks.
GLORY-1, the pivotal obesity trial, randomised 610 Chinese adults with a body mass index of at least 28, or 24 to 28 with an obesity-related comorbidity, to mazdutide 4 mg, 6 mg or placebo for 48 weeks. Mean percentage change in body weight was -11.00% (95% CI -12.27 to -9.73) at 4 mg and -14.01% (95% CI -15.36 to -12.66) at 6 mg, against +0.30% in the placebo group, which gained rather than lost weight. Weight loss of at least 15% was achieved by 35.7%, 49.5% and 2.0% respectively. Reductions were also seen in waist circumference, blood pressure, liver enzymes and serum uric acid. Baseline mean weight was 87.2 kg and mean BMI 31.1, materially lower than typical Western obesity trial populations.
The DREAMS phase 3 programme addressed type 2 diabetes. One trial compared mazdutide with placebo over 24 weeks in just over 300 Chinese adults and showed substantial HbA1c reduction; a companion trial compared mazdutide with dulaglutide and reported greater weight reduction with mazdutide alongside at least comparable glycaemic effect. Both were published together in Nature in 2026. The caveats are consistent across the programme. The evidence is almost entirely Chinese, in a population with substantially lower average body mass index than Western obesity cohorts, which limits direct extrapolation. Follow-up is short, at 24 to 48 weeks. No cardiovascular or hepatic histology outcome data have been reported, and no adequately powered head-to-head trial against semaglutide or tirzepatide has published.
Evidence assessment
High-quality evidence
Mazdutide holds regulator-approved labelling from China's National Medical Products Administration and is supported by replicated phase 3 randomised controlled trials in obesity (GLORY-1) and in type 2 diabetes (the DREAMS programme), published in the New England Journal of Medicine and Nature. All six cited studies were individually verified against PubMed. The important limitation is generalisability: the entire phase 3 evidence base was generated in Chinese populations, follow-up does not exceed 48 weeks, and no cardiovascular outcomes trial has reported.
Tiers are applied consistently across the library and re-checked when new trials read out. Read the grading method.
Key studies
A phase 1b randomised controlled trial of a glucagon-like peptide-1 and glucagon receptor dual agonist IBI362 (LY3305677) in Chinese patients with type 2 diabetes Preclinical only
Established dose-dependent reductions in glucose and body weight with an acceptable early tolerability profile, supporting once-weekly dosing.
A phase 2 randomised controlled trial of mazdutide in Chinese overweight adults or adults with obesity Preclinical only
Dose-dependent body weight reduction with accompanying improvements in waist circumference and cardiometabolic markers; gastrointestinal effects were the main tolerability issue.
Efficacy and Safety of Mazdutide in Chinese Patients With Type 2 Diabetes: A Randomized, Double-Blind, Placebo-Controlled Phase 2 Trial Preclinical only
Significant dose-dependent reductions in HbA1c and body weight versus placebo, defining the doses carried into phase 3.
Once-Weekly Mazdutide in Chinese Adults with Obesity or Overweight Preclinical only
Mean percentage change in body weight at 48 weeks was -11.00% (4 mg) and -14.01% (6 mg) against +0.30% on placebo. Weight loss of at least 15% was reached by 35.7%, 49.5% and 2.0% respectively (P<0.001). Improvements were also seen in waist circumference, blood pressure, liver enzymes and uric acid.
Mazdutide versus placebo in Chinese adults with type 2 diabetes Preclinical only
Mazdutide produced significant reductions in HbA1c and body weight relative to placebo over 24 weeks.
Mazdutide versus dulaglutide in Chinese adults with type 2 diabetes Preclinical only
Mazdutide produced greater body weight reduction than dulaglutide with at least comparable glycaemic control.
Safety
Gastrointestinal adverse effects are the most frequent and are dose-dependent, with nausea, diarrhoea, vomiting and decreased appetite concentrated during dose escalation; in GLORY-1 these were characterised as generally mild to moderate. Increases in resting heart rate have been reported, as with other GLP-1 and glucagon receptor agonists. The glucagon receptor arm creates theoretical concerns about hepatic glucose production and about protein catabolism during prolonged exposure, neither of which emerged as a clinical problem over the 24 to 48 week trial durations reported. Injection-site reactions and transient lipase elevations have been described. Because approved use is confined to China and the longest trials run to 48 weeks, there are no long-term safety data: nothing is established about cardiovascular outcomes, malignancy risk, pancreatitis at population scale, or use in pregnancy. Material obtained outside a regulated supply chain carries additional risks of unverified identity, purity and sterility.
Regulatory status
| Jurisdiction | Status |
|---|---|
| United Kingdom | Investigational. Mazdutide has no MHRA marketing authorisation and is not available on prescription or through the NHS. It is not licensed anywhere in Europe. Supply or sale as a medicine outside a clinical trial would breach the Human Medicines Regulations 2012. |
| United States | Investigational. Mazdutide has no FDA approval for any indication. Global development, including trials in non-Chinese populations, has been under way but no United States marketing application has been approved. It may lawfully be supplied in the United States only within an authorised clinical trial; material sold online is unapproved and unregulated. |
| WADA (sport) | Not prohibited. Mazdutide is not listed on the WADA Prohibited List, and dual GLP-1 and glucagon receptor agonists are not banned as a class. WADA's separate Monitoring Programme is revised annually and carries no sanctions; the list in force for the relevant year should be checked. |
Questions
No. As of August 2026 the only approvals are from China's National Medical Products Administration, granted in 2025 for chronic weight management and for glycaemic control in type 2 diabetes. It has no FDA or MHRA authorisation.
Different second receptor. Tirzepatide is a GLP-1 and GIP receptor dual agonist; mazdutide is a GLP-1 and glucagon receptor dual agonist derived from oxyntomodulin. GIP agonism is broadly anabolic and insulin-sensitising, while glucagon agonism increases energy expenditure and hepatic fat oxidation. No head-to-head trial has compared them.
Cautiously at best. The GLORY-1 population had a mean BMI of 31.1 and mean weight of 87.2 kg, well below typical Western obesity cohorts, and body composition, comorbidity patterns and dose-response can differ. Global trials in more diverse populations are needed before results can be assumed to transfer.
Oxyntomodulin is a naturally occurring gut hormone made from the same proglucagon precursor as GLP-1 and glucagon, and is itself a weak dual agonist at both receptors. Mazdutide is essentially an engineered, protease-resistant, albumin-binding version of that natural molecule.