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Mazdutide

Weight Loss

a.k.a. IBI362

GLP-1 / glucagon dual agonist

Mazdutide (also known as IBI362) is a once-weekly injectable peptide that simultaneously activates two hormone receptors in the body.

§Dosing at a glance

3 protocols · from the research
What it's forDoseHow oftenHowFor how long
Obesity / Overweight (without diabetes)4 mgOnce weekly—48 wks
Type 2 Diabetes4 mgOnce weeklyOralTaken by mouth.28 wks
Emerging / Investigational Indications4 mgOnce weeklySubcutaneousInjected just under the skin, into the fat layer.60 wks

Approximate values pulled from the research — double-check before dosing.

§01Summary

Mazdutide (also known as IBI362) is a once-weekly injectable peptide that simultaneously activates two hormone receptors in the body — the glucagon-like peptide-1 receptor (GLP-1R) and the glucagon receptor (GCGR). This dual action amplifies the metabolic benefits seen with GLP-1-only therapies: GLP-1 receptor activation suppresses appetite and improves blood sugar control, while glucagon receptor activation adds meaningful additional fat burning and energy expenditure. Together, these effects produce significant and sustained reductions in body weight and improvements in cardiometabolic health.

In large randomized controlled trials, mazdutide reduces body weight by approximately 11–14% over 48 weeks in adults with overweight or obesity1, and reduces HbA1c by up to 2.15% in people with type 2 diabetes while simultaneously producing 5–8% body weight loss over 24 weeks3. At higher investigational doses of 9 mg, weight reductions approaching 13% have been observed at 24 weeks10, and at 16 mg, early-phase data show approximately 20–21% weight loss at 20 weeks9. Mazdutide also improves a broad range of cardiometabolic markers including blood lipids, blood pressure, and fasting glucose1,3. Its gastrointestinal side effects are consistent with others in its class and are mostly mild to moderate1,2,3. Research is actively expanding into additional indications including fatty liver disease, heart failure, and adolescent obesity11,12,15,18.

This is the layperson summary. Mechanism, dosing, the evidence base, and the published literature are in the sections below — every claim links to its source.

§02In depth

Mazdutide (IBI362) is a synthetic peptide dual agonist engineered to simultaneously activate the glucagon-like peptide-1 receptor (GLP-1R) and the glucagon receptor (GCGR). It is structurally derived from the native glucagon peptide backbone, modified to confer balanced co-agonism at both receptor targets along with a fatty acid conjugation that enables extended half-life and supports once-weekly subcutaneous dosing — a pharmacokinetic profile analogous to other acylated GLP-1 receptor agonists such as semaglutide1,4.

GLP-1R activation mediates the well-characterized incretin effects: glucose-dependent stimulation of pancreatic insulin secretion, suppression of glucagon from alpha cells, delayed gastric emptying, and centrally mediated appetite suppression through hypothalamic and brainstem signaling pathways3,5. These mechanisms collectively reduce postprandial glucose excursions, lower fasting plasma glucose, reduce HbA1c, and decrease caloric intake2,3,5. GCGR co-agonism provides mechanistically distinct and additive metabolic benefits: glucagon receptor activation in the liver enhances hepatic fatty acid oxidation and increases energy expenditure through thermogenic effects, augmenting weight loss beyond what GLP-1R agonism alone achieves2,4,5. The differential weight loss magnitude between mazdutide and the pure GLP-1 agonist dulaglutide — approximately 5.76% additional weight reduction at the 6 mg dose2 — provides clinical evidence that GCGR co-agonism contributes substantively to the overall metabolic effect profile.

At the cellular level, both GLP-1R and GCGR are G protein-coupled receptors that primarily signal through the Gs/adenylyl cyclase/cAMP pathway, activating protein kinase A (PKA) and its downstream transcriptional and metabolic targets. In pancreatic beta cells, GLP-1R-mediated cAMP elevation potentiates glucose-stimulated insulin secretion in a glucose-dependent manner, which accounts for the low incremental hypoglycemia risk observed in clinical trials (approximately 10% with mazdutide versus 8% with placebo)5. GCGR-mediated signaling in brown and white adipose tissue and skeletal muscle may contribute to increased uncoupled thermogenesis and mitochondrial activity, further supporting the enhanced energy expenditure observed with dual agonism relative to GLP-1 monotherapy4,6.

Beyond glycemic and weight outcomes, mazdutide's dual receptor mechanism appears to produce broad cardiometabolic benefits, with improvements documented across lipid panels, blood pressure, and fasting metabolic biomarkers in multiple trials1,3,9. The therapeutic relevance of GCGR agonism in non-alcoholic/metabolic-associated fatty liver disease (MAFLD/MASH) — where glucagon signaling promotes hepatic lipid clearance and reduces steatosis — is an area of active clinical investigation, with Phase 2 and Phase 3 trials currently underway12,18. The dose-response relationship observed across the 3–16 mg range4,9,10 suggests that GCGR-mediated effects may scale with receptor occupancy, supporting ongoing exploration of higher-dose regimens.

§04Evidence & efficacy

Evidence base
97Studies
50Human
1Animal

Mazdutide demonstrates robust, replicated efficacy across two major therapeutic areas: obesity/overweight management and type 2 diabetes (T2D).

Weight Reduction (Obesity/Overweight):
In a Phase 3 randomized controlled trial in Chinese adults, mazdutide reduces body weight by 11.00% (4 mg) and 14.01% (6 mg) from baseline at 48 weeks, compared to approximately +0.30% with placebo (P<0.001)1. At week 32, 73.9% and 82.0% of participants in the 4 mg and 6 mg groups, respectively, achieved ≥5% weight reduction versus 10.5% with placebo1. At 48 weeks, ≥15% weight loss was achieved by 35.7% (4 mg) and 49.5% (6 mg) of participants versus 2.0% with placebo1. Phase 2 dose-finding data confirm a clear dose-response relationship, with reductions of 6.7% (3 mg), 10.4% (4.5 mg), and 11.3% (6 mg) at 24 weeks versus +1.0% with placebo4. At the investigational 9 mg dose, weight reduction reaches 12.78% at 24 weeks versus +1.80% with placebo10, and at 16 mg, approximately 20–21% weight loss appears achievable at 20 weeks9.

Glycemic Control and Weight in Type 2 Diabetes:
Mazdutide reduces HbA1c by 1.57% (4 mg) and 2.15% (6 mg) versus 0.14% with placebo at 24 weeks in T2D patients (both P<0.0001)3, with concurrent body weight reductions of 5.61% and 7.81% respectively3. In an active-controlled Phase 3 trial versus dulaglutide 1.5 mg, mazdutide demonstrates superiority on both HbA1c reduction (differences of −0.24% and −0.30% for 4 mg and 6 mg respectively) and body weight reduction (differences of −3.78% and −5.76%)2. Phase 2 data further confirm that mazdutide numerically outperforms dulaglutide on glycemic outcomes and produces substantially greater weight loss5.

Cardiometabolic Markers:
Mazdutide improves a broad range of prespecified cardiometabolic endpoints including lipids, blood pressure, and fasting glucose across multiple trials1,3. Network meta-analysis confirms that GLP-1/glucagon dual agonists as a class, including mazdutide, produce superior weight loss compared to GLP-1 mono-agonists, though agents such as retatrutide and tirzepatide ranked higher in the network for absolute weight reduction6.

Emerging Indications:
Efficacy in MAFLD/MASH12,18, HFpEF/HFmrEF15, hypertension17, adolescent obesity11, and as post-bariatric surgical adjunct therapy19 is being established through ongoing Phase 2 and Phase 3 trials.

§05Safety

Mazdutide's safety profile across completed trials is consistent with the broader GLP-1 receptor agonist drug class. The most frequently reported adverse events are gastrointestinal in nature, including diarrhea, nausea, vomiting, and decreased appetite1,2,3,4,5. These events are predominantly mild to moderate in severity and do not commonly lead to treatment discontinuation1.

In the 48-week Phase 3 obesity trial, discontinuation rates due to adverse events were notably low at 1.5% (4 mg), 0.5% (6 mg), and 1.0% (placebo)1, which compares favorably with other incretin-based therapies. In the 28-week Phase 3 diabetes trial versus dulaglutide, the incidence of gastrointestinal adverse events was higher with both mazdutide doses compared to dulaglutide 1.5 mg, though the overall safety profile was described as generally safe2. In phase 2 diabetes studies, diarrhea occurred in approximately 36% of mazdutide-treated patients, decreased appetite in 29%, nausea in 23%, and vomiting in 14%5. At the higher 9 mg dose, nausea was reported in 50%, diarrhea in 38.3%, and vomiting in 36.7% of participants, though events remained predominantly mild to moderate10.

Hypoglycemia risk appears low; in phase 2 diabetes trials, hypoglycemia occurred in approximately 10% of mazdutide-treated patients versus 8% with placebo, indicating minimal incremental hypoglycemia risk5. Across the meta-analytic evidence base for GLP-1/glucagon dual agonists, no significant increase in serious adverse events was observed (OR = 1.03; P = 0.91)7. No unexpected safety signals have been reported across completed trials3,4,5.

Safety in adolescents11, heart failure patients15, MASH18, and post-bariatric surgery populations19 is currently being investigated in registered trials with results pending.

§06History

Mazdutide (development code IBI362) was developed by Innovent Biologics (Suzhou) Co. Ltd., a Chinese biopharmaceutical company, as part of a broader research effort to advance incretin-based therapies with enhanced metabolic efficacy through receptor polyagonism. The compound belongs to the class of GLP-1/glucagon receptor dual agonists, a mechanistic approach that gained scientific traction in the 2010s following preclinical demonstrations that co-stimulation of both receptors could produce synergistic effects on weight loss and metabolic homeostasis beyond what GLP-1 monotherapy could achieve4,5.

Early-phase clinical investigation of mazdutide began in Chinese adults, with Phase 2 proof-of-concept trials in type 2 diabetes establishing glycemic efficacy and a favorable safety profile across doses ranging from 3 mg to 6 mg weekly5. Subsequent Phase 2 trials in overweight and obese adults without diabetes confirmed robust dose-dependent weight loss, with the 6 mg dose achieving approximately 11.3% body weight reduction at 24 weeks4, providing the pharmacological rationale for advancing to Phase 3. The pivotal 48-week Phase 3 obesity trial, published in the New England Journal of Medicine in 2025, confirmed 11–14% weight loss at the 4 mg and 6 mg doses1, representing a landmark publication for the compound. Parallel Phase 3 trials in type 2 diabetes were published in Nature in 2025, confirming superiority over both placebo3 and the established GLP-1 agonist dulaglutide2. Dose-expansion studies exploring 9 mg10 and 16 mg9 doses have been completed or reported, and mazdutide is now in active Phase 3 development for multiple additional indications including MAFLD12, MASH18, HFpEF15, hypertension17, adolescent obesity11, and as a post-bariatric surgery adjunct19.

§07References