Mazdutide
Also known as: IBI362, LY3305677, Xinermei
6 notable studies · 7 references
TLDR
Mazdutide is a once-weekly GLP-1/glucagon dual-receptor agonist with substantial Phase 2 and Phase 3 evidence for weight reduction and glycemic control and is approved in China for weight management and type 2 diabetes, while development and regulatory evaluation outside China continue. PubMed
Research Supports
- Studied for dose-dependent weight reduction in adults with overweight or obesity
- Studied for glycemic control (HbA1c reduction) in type 2 diabetes
- Investigated for combined GLP-1/glucagon receptor effects on hepatic and energy metabolism
- Examined for cardiometabolic risk-factor changes alongside weight loss
- Investigated in metabolic dysfunction-associated fatty liver disease and obstructive sleep apnea
Observations Reported in Research
- 2023 Phase 2 (n=248): 24-week weight change −6.7% to −11.3% across doses vs. +1.0% with placebo
- 2026 Phase 2 (n=80): 9 mg produced −12.78% weight change vs. +1.80% with placebo at 24 weeks
- DREAMS-1 Phase 3 (n=320): HbA1c −1.57% to −2.15% and weight −5.61% to −7.81% vs. placebo at 24 weeks
- Common adverse events across trials included diarrhea, nausea, and vomiting, mostly mild-to-moderate
- A 2026 systematic review found mazdutide among the dual agonists producing the largest weight effects in its class
These are brief summaries of what the referenced research examined or reported — not conclusions about safety or effectiveness, and not medical advice. See Notable Studies and Sources & References below for the full context and citations.
At a Glance
Classification: Long-acting peptide dual agonist of the glucagon-like peptide-1 receptor (GLP-1R) and glucagon receptor (GCGR)
Mazdutide is a once-weekly peptide that simultaneously activates GLP-1 and glucagon receptors. That makes it mechanistically different from semaglutide, tirzepatide, and retatrutide: Semaglutide → GLP-1 Tirzepatide → GLP-1 + GIP Mazdutide → GLP-1 + glucagon Retatrutide → GLP-1 + GIP + glucagon The idea behind mazdutide is particularly interesting because GLP-1 and glucagon can contribute complementary metabolic effects. GLP-1 signaling can decrease food intake and improve glucose regulation, while glucagon-receptor signaling can influence hepatic metabolism and energy expenditure. Mazdutide now has substantial Phase 2 and Phase 3 human evidence. In June 2025, China approved mazdutide for long-term weight management in qualifying adults with obesity or overweight. In September 2025, China approved it for glycemic control in adults with type 2 diabetes. PubMed Development continues internationally, including a recently published 48-week U.S. Phase 2 obesity trial. PubMed
What Is Mazdutide?
Mazdutide is a synthetic long-acting peptide engineered to activate two metabolically important receptors: GLP-1R — glucagon-like peptide-1 receptor and GCGR — glucagon receptor It originated from the same broader research program that produced oxyntomodulin-inspired dual agonists. Natural oxyntomodulin is an intestinal peptide capable of activating both GLP-1 and glucagon receptors, but its short biological half-life makes it unsuitable as a once-weekly medication. Mazdutide was engineered to reproduce this dual-receptor concept while providing substantially prolonged exposure. The resulting pharmacology attempts to combine reduced energy intake and improved glycemic regulation from GLP-1 signaling with metabolic effects associated with glucagon-receptor activation.
What Are Researchers Studying?
Obesity and body-weight regulation
Weight management has been one of mazdutide's principal development programs. A 2023 Phase 2 trial randomized 248 Chinese adults with overweight or obesity to weekly mazdutide or placebo. After 24 weeks, average body-weight changes were: 3 mg: −6.7% 4.5 mg: −10.4% 6 mg: −11.3% Placebo: +1.0% The results demonstrated a clear dose-response relationship. PubMed A subsequent higher-dose study found an average 12.78% reduction with 9 mg at 24 weeks, versus a 1.80% increase with placebo. PubMed
Type 2 diabetes
Mazdutide has substantial human evidence for glycemic regulation. A Phase 2 study in adults with type 2 diabetes found average HbA1c reductions of approximately 1.41–1.67 percentage points after 20 weeks across mazdutide doses up to 6 mg. Weight reduction reached approximately 7.1% at the highest studied dose. PubMed Phase 3 evidence subsequently strengthened these findings. In DREAMS-1, 320 adults with inadequately controlled type 2 diabetes received mazdutide or placebo. At 24 weeks: Mazdutide 4 mg: HbA1c −1.57%; weight −5.61% Mazdutide 6 mg: HbA1c −2.15%; weight −7.81% Placebo: HbA1c −0.14%; weight −1.26%. PubMed These and other data supported mazdutide's 2025 Chinese approval for glycemic control.
Glucagon-receptor signaling and energy expenditure
The glucagon component is what makes mazdutide particularly interesting scientifically. GLP-1 receptor activation primarily contributes to reduced food intake and improved glucose regulation. Glucagon-receptor activation can influence: • Hepatic metabolism • Lipid metabolism • Substrate utilization • Energy expenditure • Amino-acid metabolism The research hypothesis is that appropriately balanced glucagon signaling may add metabolic effects beyond those produced by GLP-1 signaling alone. The challenge is that glucagon can also increase hepatic glucose production. Successful dual agonism therefore requires a pharmacological balance in which GLP-1-mediated metabolic effects counter undesirable hyperglycemic effects while preserving potentially useful glucagon biology.
Cardiometabolic risk factors
Clinical trials have reported improvements in several cardiometabolic measurements alongside weight reduction. These include changes in: • Waist circumference • Blood pressure • Triglycerides • Cholesterol-related measurements • Glucose regulation • Insulin resistance markers A 2026 systematic review of GLP-1/glucagon dual agonists found improvements across body weight, HbA1c, waist circumference, systolic blood pressure and triglycerides, with mazdutide and survodutide producing some of the largest weight effects in the class. PubMed These changes should not yet be interpreted as proof that mazdutide prevents cardiovascular events.
Metabolic dysfunction-associated fatty liver disease
Glucagon signaling makes liver metabolism a particularly important area of mazdutide research. Clinical development has expanded into metabolic liver disease, including studies involving metabolic dysfunction-associated fatty liver disease and MASH. China's approved obesity indication also recognizes fatty liver disease among relevant weight-related comorbidities. Innovent Bio Whether mazdutide ultimately produces clinically meaningful improvements in fibrosis or long-term liver outcomes remains an active research question.
Obstructive sleep apnea
Mazdutide is being investigated in obesity-associated obstructive sleep apnea. This follows a broader trend in obesity-drug development in which researchers increasingly evaluate whether substantial weight reduction improves specific obesity-related diseases rather than simply measuring body weight. Clinical development in this area is ongoing. PubMed
Adolescent obesity
Mazdutide development has expanded into younger populations. In 2026, Innovent reported Phase 1b research evaluating mazdutide in Chinese adolescents with obesity. These studies represent early pediatric development and should not be generalized from the established adult indications in China. Innovent Bio
How Does It Work?
Mazdutide simultaneously activates: GLP-1R GLP-1 receptor signaling can: • Reduce appetite and energy intake • Increase glucose-dependent insulin secretion • Suppress inappropriate glucagon secretion in hyperglycemic states • Influence gastrointestinal physiology • Improve glycemic control GCGR Glucagon receptor signaling primarily affects the liver and systemic energy metabolism. It can: • Increase hepatic glucose production • Increase lipid oxidation • Affect amino-acid metabolism • Increase energy expenditure under some conditions That combination initially sounds counterintuitive. Why activate glucagon when treating diabetes? Because glucagon has potentially useful metabolic effects beyond raising glucose. The goal of a balanced dual agonist is to combine those effects with sufficiently strong GLP-1 activity to maintain or improve glucose control. Human trials show that this is pharmacologically possible: despite activating GCGR, mazdutide substantially reduced HbA1c in people with type 2 diabetes. PubMed
What Does the Research Show?
Human research
Mazdutide has progressed far beyond proof-of-concept research. Its evidence base now includes: • Phase 1 studies • Multiple Phase 2 trials • Phase 3 obesity trials • Phase 3 diabetes trials • Active-comparator trials • Higher-dose studies • U.S. clinical development • Regulatory approval in China A 2026 meta-analysis identified nine randomized trials involving 2,292 participants with obesity/overweight and/or type 2 diabetes. PubMed Importantly, the evidence is no longer exclusively Chinese. A U.S.-based multicenter randomized Phase 2 trial published in 2026 evaluated weekly mazdutide at doses up to 16 mg for 48 weeks in adults with obesity or overweight without diabetes. PubMed That study is particularly important for Aminodex because it begins answering whether the efficacy and tolerability observed in Chinese trials generalize to a U.S. population.
Animal research
Preclinical development examined the combined effects of GLP-1 and glucagon receptor activation on: • Food intake • Body weight • Energy expenditure • Glucose regulation • Hepatic metabolism • Lipid metabolism These experiments helped establish the rationale for balanced dual agonism. Preclinical work was also important for determining receptor potency and avoiding excessive glucagon activity capable of overwhelming the glucose-lowering effects of GLP-1 signaling. Human clinical evidence has now become substantially more important than the original animal evidence for evaluating mazdutide's efficacy.
In-vitro research
Cellular receptor assays established that mazdutide activates both human GLP-1R and GCGR. These experiments are important because dual agonist is a pharmacological description, not simply a marketing category. Receptor studies allow investigators to determine: • Relative receptor potency • Signaling efficacy • Duration of receptor activation • Receptor selectivity • How structural modifications change the GLP-1/glucagon balance The exact balance between these two receptors may ultimately help explain differences among mazdutide, survodutide, cotadutide and other dual agonists.
Notable Studies
A Phase 2 Randomised Controlled Trial of Mazdutide in Chinese Overweight Adults or Adults With Obesity
humanResearchers randomized 248 Chinese adults with overweight or obesity to weekly mazdutide 3 mg, 4.5 mg, 6 mg or placebo. At 24 weeks, average weight changes were: 3 mg: −6.7% 4.5 mg: −10.4% 6 mg: −11.3% Placebo: +1.0% Common adverse events included diarrhea, nausea and upper-respiratory-tract infection. The study established substantial dose-dependent weight reduction with mazdutide. PubMed
Limitations: The trial lasted 24 weeks and involved a Chinese population. It could not establish long-term cardiovascular outcomes, mortality effects or multi-year durability.
View publication →Efficacy and Safety of Mazdutide in Chinese Patients With Type 2 Diabetes: A Randomized, Double-Blind, Placebo-Controlled Phase 2 Trial
humanAdults with inadequately controlled type 2 diabetes received mazdutide 3, 4.5 or 6 mg, dulaglutide 1.5 mg, or placebo. At week 20, average HbA1c reductions ranged from 1.41 to 1.67 percentage points with mazdutide. Average weight reduction was dose-dependent and reached approximately 7.1%, compared with 2.7% with dulaglutide and 1.4% with placebo. PubMed
Limitations: Treatment lasted only 20 weeks. The trial was not powered for cardiovascular or long-term safety outcomes.
View publication →Mazdutide Versus Placebo in Chinese Adults With Type 2 Diabetes
humanResearchers randomized 320 adults with type 2 diabetes to mazdutide 4 mg, mazdutide 6 mg or placebo. At 24 weeks, average HbA1c changes were: 4 mg: −1.57% 6 mg: −2.15% Placebo: −0.14% Average weight changes were: 4 mg: −5.61% 6 mg: −7.81% Placebo: −1.26%. The study provided Phase 3 evidence that dual GLP-1/glucagon receptor activation can improve glycemic control despite the glucose-raising physiology ordinarily associated with glucagon. PubMed
Limitations: Participants were Chinese adults and the placebo-controlled primary period lasted 24 weeks. Long-term cardiovascular outcomes were not established.
View publication →Mazdutide Versus Dulaglutide in Chinese Adults With Type 2 Diabetes
humanDREAMS-2 directly compared mazdutide with the established GLP-1 receptor agonist dulaglutide in adults with type 2 diabetes. The trial evaluated glycemic control, body weight and metabolic outcomes and expanded the evidence base beyond placebo-controlled testing. PubMed
Limitations: The trial population was Chinese, and comparison with dulaglutide does not establish superiority to newer agents such as tirzepatide or semaglutide at obesity-treatment doses.
View publication →Mazdutide 9 mg in Chinese Adults With a Body Mass Index ≥30 kg/m² but Without Diabetes: A Phase 2 Randomized Controlled Trial
humanEighty adults with obesity without diabetes received mazdutide 9 mg or placebo for 24 weeks. Average weight change was: Mazdutide: −12.78% Placebo: +1.80% The treatment difference was −14.58 percentage points. Nausea occurred in 50.0%, diarrhea in 38.3%, and vomiting in 36.7% of mazdutide-treated participants; most gastrointestinal events were mild-to-moderate. PubMed
Limitations: Only 80 participants were randomized, and treatment lasted 24 weeks. The trial does not establish multi-year efficacy or safety.
View publication →Efficacy and Safety of Mazdutide in Adults With Obesity or Overweight: A US-Based, Multicentre, Phase 2, Randomised, Placebo-Controlled Clinical Trial
humanResearchers evaluated once-weekly mazdutide across doses up to 16 mg for 48 weeks at 24 U.S. centers in adults with obesity or overweight without type 2 diabetes. This represents an important expansion of the mazdutide evidence base beyond China and evaluates substantially higher doses than the currently approved Chinese obesity regimens. PubMed
Limitations: This remains Phase 2 research and does not itself establish U.S. regulatory approval, long-term cardiovascular benefit or multi-year safety.
View publication →What We Still Don't Know
Important unanswered questions include: • Long-term cardiovascular outcomes • Effects on cardiovascular mortality • Multi-year durability of weight reduction • Weight regain following discontinuation • Long-term consequences of chronic glucagon-receptor stimulation • Effects on lean mass and body composition • Long-term hepatic outcomes • Whether glucagon activation provides clinically meaningful advantages over GLP-1-only treatment • How mazdutide compares with tirzepatide • How it compares with retatrutide • How it compares with other GLP-1/glucagon agonists such as survodutide • Whether higher-dose mazdutide changes its benefit-risk profile • Whether efficacy differs meaningfully among populations • Its eventual U.S. regulatory status A head-to-head Phase 3 program is also comparing mazdutide with semaglutide in Chinese adults with type 2 diabetes and obesity, making direct-comparator evidence especially important to watch. PubMed
Related Compounds
Recent publications
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Sources & References
- Ji L, et al. A Phase 2 Randomised Controlled Trial of Mazdutide in Chinese Overweight Adults or Adults With Obesity. Nature Communications. 2023;14:8289.
- Efficacy and Safety of Mazdutide in Chinese Patients With Type 2 Diabetes: A Randomized, Double-Blind, Placebo-Controlled Phase 2 Trial. Diabetes Care. 2023.
- Guo L, Zhang B, Xue X, et al.; DREAMS-2 Investigators. Mazdutide Versus Dulaglutide in Chinese Adults With Type 2 Diabetes. Nature. 2026;652:181–188.
- DREAMS-1 Investigators. Mazdutide Versus Placebo in Chinese Adults With Type 2 Diabetes. Nature. 2025/2026.
- Ji L, Jiang H, Cheng Z, et al. Mazdutide 9 mg in Chinese Adults With a Body Mass Index ≥30 kg/m² but Without Diabetes: A Phase 2 Randomized Controlled Trial. Med. 2026;7:101063.
- Hsia SH, et al. Efficacy and Safety of Mazdutide in Adults With Obesity or Overweight: A US-Based, Multicentre, Phase 2, Randomised, Placebo-Controlled Clinical Trial. Lancet Diabetes & Endocrinology. 2026.
- Syed YY. Mazdutide: First Approval. Drugs. 2025.
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