peptidechats
Research information only. Not medical advice. 18+ only. Not FDA-approved for human therapeutic use.

Mazdutide

Also known as: IBI362, LY3305677, LY3305677, Xinermei

Dual glucagon receptor (GCGR) / glucagon-like peptide-1 receptor (GLP-1R) agonist; incretin-based peptide therapeutic

Ask about Mazdutide in chat →

What it is

Mazdutide is a once-weekly dual agonist that simultaneously activates the glucagon receptor (GCGR) and the glucagon-like peptide-1 receptor (GLP-1R) (PMID 41028652; PMID 36247927). GLP-1R agonism stimulates insulin secretion and reduces blood glucose, while GCGR agonism is believed to enhance energy expenditure, stimulate lipolysis and mitochondrial fat oxidation in the liver, reduce caloric intake, and increase energy expenditure — mechanisms primarily characterised in preclinical rodent models, with limited direct human mechanistic data (PMID 41478576; PMID 41025406). The concurrent GLP-1R activation counterbalances the hyperglycaemic effects of glucagon. Through this dual mechanism, mazdutide produces dose-dependent reductions in body weight, HbA1c, and multiple cardiometabolic risk factors (PMID 41028652; PMID 41407860; PMID 41407859). Preclinical evidence additionally indicates that GCGR activation in renal tubular cells exerts renoprotective effects via a GCGR–ATP6V1A–lysosome axis that preserves lysosomal acidification and autophagic flux. In a diabetic mouse model, mazdutide improved cognitive performance and neuroprotective molecular pathways compared with a GLP-1R monoagonist, attributed to dual GLP-1/GCGR activation.

Class: Dual glucagon receptor (GCGR) / glucagon-like peptide-1 receptor (GLP-1R) agonist; incretin-based peptide therapeutic

What it's studied for

  • Weight reduction in adults with overweight or obesity (without diabetes) Human RCT
    • Phase 3 RCT (n=610, China). At week 32, mean body-weight change: -10.09% (4 mg), -12.55% (6 mg) vs +0.45% (placebo). At week 48: -11.00% (4 mg) and -14.01% (6 mg) vs +0.30% (placebo). ≥5% weight loss at week 32: 73.9% (4 mg), 82.0% (6 mg) vs 10.5% (placebo). P<0.001 for all comparisons. PMID 40421736 Ji L et al. Once-Weekly Mazdutide in Chinese Adults with Obesity or Overweight. N Engl J Med (2025).
    • Phase 3 RCT (n=461, China, BMI ≥30, 16.1% with T2D). At week 60, mean body-weight change: -16.65% (mazdutide 9 mg) vs -1.50% (placebo); between-group difference -15.15% (P<0.001). 84.3% vs 33.1% achieved ≥5% weight loss. PMID 42251595 Gao L et al. Treatment With 9-mg Mazdutide for Weight Reduction in Chinese Adults With Obesity: The GLORY-2 Randomized Clinical Trial. JAMA (2026).
    • Phase 2 RCT (n=248, China). Mean body-weight change at week 24: -6.7% (3 mg), -10.4% (4.5 mg), -11.3% (6 mg) vs +1.0% (placebo); treatment difference vs placebo -7.7% to -12.3% (all P<0.0001). PMID 38092790 Ji L et al. A phase 2 randomised controlled trial of mazdutide in Chinese overweight adults or adults with obesity. Nat Commun (2023).
    • Phase 2 RCT (n=80, China, BMI ≥30, no diabetes). At week 24, mean body-weight change: -12.78% (mazdutide 9 mg) vs +1.80% (placebo); treatment difference -14.58% (P<0.0001). 81.7% of mazdutide recipients achieved ≥5% weight loss; 0% in placebo. PMID 41875890 Ji L et al. Mazdutide 9 mg in Chinese adults with a BMI ≥30 kg/m² but without diabetes: A phase 2 RCT. Med (2026).
    • Phase 1 RCT (n=32, non-Chinese adults without diabetes). At week 20, mean body-weight change: -20.0% (Cohort 1, target 16 mg) and -21.0% (Cohort 2, target 16 mg) vs -0.1% (placebo; P<0.001). ≥15% weight loss: 66.7% (Cohort 1), 75.0% (Cohort 2). PMID 40832785 Bhattachar SN et al. Mazdutide reduces body weight in adults with overweight or obesity: A high-dose Phase 1 trial. Diabetes Obes Metab (2025).
    • Phase 2 RCT (n=179, USA, no T2D). At week 32, LS mean body-weight change: -7.3% (3-6 mg), -15.6% (10 mg), -18.1% (16 mg) vs -0.9% (placebo); treatment differences -6.5% to -17.2% (P<0.0001 all comparisons). PMID 42628555 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 Endocrinol (2026).
    • Phase 1b RCT (n=24, China). Mean body-weight change at week 12: -11.7% (mazdutide 9 mg) vs -1.8% (placebo; ETD -9.8%; P=0.0002). At week 16 (10 mg cohort): -9.5% vs -3.3% (ETD -6.2%; P=0.024). PMID 36247927 Ji L et al. Safety and efficacy of mazdutide 9 mg and 10 mg in Chinese adults with overweight or obesity: A phase 1b trial. EClinicalMedicine (2022).
  • Glycaemic control in adults with type 2 diabetes (T2D) Human RCT
    • Phase 3 RCT (n=320, China). At week 24, HbA1c change: -1.57% (4 mg) and -2.15% (6 mg) vs -0.14% (placebo); treatment differences -1.43% and -2.01% (both P<0.0001). Weight loss: -5.61% (4 mg), -7.81% (6 mg) vs -1.26% (placebo; both P<0.0001). PMID 41407859 Zhu D et al. Mazdutide versus placebo in Chinese adults with type 2 diabetes. Nature (2026).
    • Phase 3 RCT (n=731, China). Mazdutide 4 mg and 6 mg non-inferior and superior to dulaglutide 1.5 mg for HbA1c reduction (LS mean treatment difference: -0.24% for 4 mg, P=0.0032; -0.30% for 6 mg, P=0.0003). Body-weight reduction superior to dulaglutide: LS mean treatment difference -3.78% (4 mg) and -5.76% (6 mg; both P PMID 41407860 Guo L et al. Mazdutide versus dulaglutide in Chinese adults with type 2 diabetes. Nature (2026).
    • Phase 2 RCT (n=250, China). HbA1c change at week 20: -1.41% to -1.67% with mazdutide (3 mg, 4.5 mg, 6 mg) vs +0.03% with placebo (all P<0.0001 vs placebo). Body-weight change: dose-dependent, up to -7.1% with mazdutide vs -1.4% with placebo. PMID 37943529 Zhang B et al. Efficacy and Safety of Mazdutide in Chinese Patients With Type 2 Diabetes: A Randomized, Double-Blind, Placebo-Controlled Phase 2 Trial. Diabetes Care (2024).
    • Phase 1b RCT (n=42, China). IBI362 (mazdutide) 3.0, 4.5, and 6.0 mg subcutaneously for 12 weeks reduced HbA1c, fasting plasma glucose, and post-meal glucose from baseline in all cohorts. Drug was well tolerated. PMID 35750681 Jiang H et al. A phase 1b RCT of IBI362 (LY3305677) in Chinese patients with type 2 diabetes. Nat Commun (2022).
  • Obesity management in adults with type 2 diabetes and obesity Human RCT
    • Phase 3 RCT design: mazdutide 6 mg vs semaglutide 1 mg once weekly for 32 weeks (+ 24-week extension) in Chinese adults with T2D and BMI ≥28 kg/m². Primary endpoint: proportion achieving HbA1c <7.0% and weight reduction ≥10% at week 32. Baseline data reported; results pending. PMID 41260459 Luo Y et al. Mazdutide versus Semaglutide for the treatment of type 2 diabetes and obesity: Rationale, design and baseline data of DREAMS-3 phase 3 trial. Contemp Clin Trials (2026).
    • Subgroup included 16.1% with T2D. Mean body-weight change -16.65% vs -1.50% for placebo at 60 weeks (P<0.001) across the full study population including those with T2D. PMID 42251595 Gao L et al. Treatment With 9-mg Mazdutide for Weight Reduction in Chinese Adults With Obesity: The GLORY-2 Randomized Clinical Trial. JAMA (2026).
  • Metabolic dysfunction-associated steatotic liver disease (MASLD) / fatty liver disease Animal studies only
    • In a high-fat diet mouse model and in vitro hepatocyte model, mazdutide (100, 200, 400 µg/kg subcutaneously for 4 weeks; 10, 20, 50 nM in vitro) reduced hepatic lipid accumulation, liver injury markers, and inflammation, and suppressed ER stress via PERK pathway modulation and NF-κB–mediated inflammatory responses. PMID 41901218 Gan L et al. Mazdutide Ameliorates Metabolic Dysfunction-Associated Steatotic Liver Disease by Modulating Endoplasmic Reticulum Stress, Improving Lipid Metabolism and Alleviating Inflammation. Pharmaceuticals (Basel) (2026).
    • In high-fat diet male C57BL/6 mice, subcutaneous mazdutide (every 3 days for 4 weeks) produced greater reduction in MRI-derived hepatic fat fraction (PDFF) than semaglutide after 4 weeks (median PDFF change -5.59% vs -3.30%; P=0.02). No significant difference in hepatic iron content (R2*) between groups. PMID 40828048 Xia H et al. Multiparametric MRI Evaluation of Liver Fat and Iron after GLP-1R/GCGR Dual-Agonist Treatment in a High-Fat Diet-induced Mouse Model. Radiology (2025).
  • Diabetic kidney disease / renoprotection Animal studies only
    • Tubular GCGR signalling exerts a renoprotective role in diabetic kidney disease (DKD) in mouse models and correlates with kidney function in human DKD samples. Clinical trials of dual GLP-1R/GCGR agonists including mazdutide were cited as providing kidney benefits in T2D/CKD patients, but the primary mechanistic eviden PMID 42555719 Qu H et al. Renoprotective effects of tubular glucagon receptor activation mediated by V-ATPase. Sci Adv (2026).
  • Diabetes-associated cognitive dysfunction Animal studies only
    • In male db/db mice (T2D model), mazdutide significantly improved cognitive performance and neuronal/brain tissue integrity vs dulaglutide, with multi-omics analysis identifying distinct pathways in neuroprotection, energy metabolism, and synaptic plasticity. All findings are applicable to male mice only. PMID 40479843 Dong W et al. Mazdutide, a dual agonist targeting GLP-1R and GCGR, mitigates diabetes-associated cognitive dysfunction: mechanistic insights from multi-omics analysis. EBioMedicine (2025).
  • Hyperuricemia reduction Mixed
    • Meta-analysis of 9 RCTs found mazdutide improved uric acid levels in adults with overweight/obesity and/or T2D, among other metabolic outcomes. PMID 42410325 Kamrul-Hasan ABM et al. Efficacy and Safety of Mazdutide in Predominantly Chinese Adults With Obesity and/or T2D: A Systematic Review and Meta-Analysis. Diabetes Obes Metab (2026).
    • Single case report: 15-year-old male with obesity, T2DM, and hyperuricemia. After 36 weeks of dose-escalated mazdutide (2→4→6 mg subcutaneously once weekly), serum uric acid dropped by 37.00%. PMID 41030857 Cheng W et al. Case Report: Efficacy and safety of dose-escalated Mazdutide in an adolescent with obesity, type 2 diabetes, and hyperuricemia. Front Endocrinol (2025).
  • Cardiometabolic risk factor reduction (blood pressure, lipids, waist circumference) Human RCT
    • Meta-analysis of 5 RCTs (non-diabetic patients): mazdutide significantly reduced systolic blood pressure (MD -7.68 mmHg), total cholesterol (MD -0.57 mmol/L), and LDL (MD -0.37 mmol/L) vs placebo. PMID 41804840 Azam MH et al. Efficacy and Safety of Mazdutide in Managing Overweight and Obesity Among Non-Diabetic Adults: A Meta-Analysis of RCTs. Diabetes Obes Metab (2026).
    • Meta-analysis of 7 RCTs: mazdutide reduced systolic BP (MD -7.57 mmHg), diastolic BP (MD -2.98 mmHg), total cholesterol (MD -16.82%), triglycerides (MD -43.29%), LDL (MD -17.07%) vs placebo. PMID 38440786 Nalisa DL et al. Efficacy and safety of Mazdutide on weight loss among diabetic and non-diabetic patients: a systematic review and meta-analysis of RCTs. Front Endocrinol (2024).

Community-reported dosing

RouteDoseFrequency / DurationPopulation / contextSource tier
Subcutaneous injection3.0 mg, 4.5 mg, or 6.0 mg once weekly12 weekshumanResearch PMID 35750681
Subcutaneous injection9 mg once weekly (escalating: 3 mg weeks 1–4; 6 mg weeks 5–8; 9 mg weeks 9–12); 10 mg once weekly (escalating: 2.5 mg weeks 1–4; 5 mg weeks 5–8; 7.5 mg weeks 9–12; 10 mg weeks 13–16)12 weeks (9 mg cohort); 16 weeks (10 mg cohort)humanResearch PMID 36247927
Subcutaneous injection3 mg, 4.5 mg, or 6 mg once weekly20 weekshumanResearch PMID 37943529
Subcutaneous injection3 mg, 4.5 mg, or 6 mg once weekly24 weekshumanResearch PMID 38092790
Subcutaneous injection4 mg or 6 mg once weekly24 weeks (primary endpoint) followed by 24-week extended treatmenthumanResearch PMID 41407859
Subcutaneous injection4 mg or 6 mg once weekly28 weekshumanResearch PMID 41407860
Subcutaneous injection4 mg or 6 mg once weekly48 weeks (primary endpoint at week 32)humanResearch PMID 40421736
Subcutaneous injection9 mg once weekly24 weekshumanResearch PMID 41875890
Subcutaneous injection9 mg once weekly60 weekshumanResearch PMID 42251595
Subcutaneous injectionUp to 16 mg once weekly (two escalation regimens to 16 mg target dose)20 weekshumanResearch PMID 40832785
Subcutaneous injection3–6 mg (maintained 3 mg to week 32 then escalated to 6 mg), 10 mg, or 16 mg once weekly48 weekshumanResearch PMID 42628555
Subcutaneous injectionDose-escalation: 2 mg → 4 mg → 6 mg once weekly (in combination with metformin and insulin)36 weekshumanResearch PMID 41030857
Subcutaneous injection100, 200, or 400 µg/kg4 weeks (after 12-week high-fat diet induction)animalResearch PMID 41901218
In vitro (cell culture)10, 20, or 50 nMCo-treatment period (in vitro)in_vitroResearch PMID 41901218
Subcutaneous injectionNot explicitly stated (administered every 3 days for 4 weeks)4 weeksanimalResearch PMID 40828048

Tier key: Research = PMID-cited study · [C] = scraped community source · [S] = model-synthesized from aggregate community reports (softer evidence). How we source.

References

  1. [1] PMID 40421736 — Phase 3 RCT (n=610, China). At week 32, mean body-weight change: -10.09% (4 mg), -12.55% (6 mg) vs +0.45% (placebo). At week 48: -11.00% (4 mg) and -14.01% (6 m
  2. [2] PMID 42251595 — Phase 3 RCT (n=461, China, BMI ≥30, 16.1% with T2D). At week 60, mean body-weight change: -16.65% (mazdutide 9 mg) vs -1.50% (placebo); between-group difference
  3. [3] PMID 38092790 — Phase 2 RCT (n=248, China). Mean body-weight change at week 24: -6.7% (3 mg), -10.4% (4.5 mg), -11.3% (6 mg) vs +1.0% (placebo); treatment difference vs placebo
  4. [4] PMID 41875890 — Phase 2 RCT (n=80, China, BMI ≥30, no diabetes). At week 24, mean body-weight change: -12.78% (mazdutide 9 mg) vs +1.80% (placebo); treatment difference -14.58%
  5. [5] PMID 40832785 — Phase 1 RCT (n=32, non-Chinese adults without diabetes). At week 20, mean body-weight change: -20.0% (Cohort 1, target 16 mg) and -21.0% (Cohort 2, target 16 mg
  6. [6] PMID 42628555 — Phase 2 RCT (n=179, USA, no T2D). At week 32, LS mean body-weight change: -7.3% (3-6 mg), -15.6% (10 mg), -18.1% (16 mg) vs -0.9% (placebo); treatment differenc
  7. [7] PMID 36247927 — Phase 1b RCT (n=24, China). Mean body-weight change at week 12: -11.7% (mazdutide 9 mg) vs -1.8% (placebo; ETD -9.8%; P=0.0002). At week 16 (10 mg cohort): -9.5
  8. [8] PMID 41407859 — Phase 3 RCT (n=320, China). At week 24, HbA1c change: -1.57% (4 mg) and -2.15% (6 mg) vs -0.14% (placebo); treatment differences -1.43% and -2.01% (both P<0.000
  9. [9] PMID 41407860 — Phase 3 RCT (n=731, China). Mazdutide 4 mg and 6 mg non-inferior and superior to dulaglutide 1.5 mg for HbA1c reduction (LS mean treatment difference: -0.24% fo
  10. [10] PMID 37943529 — Phase 2 RCT (n=250, China). HbA1c change at week 20: -1.41% to -1.67% with mazdutide (3 mg, 4.5 mg, 6 mg) vs +0.03% with placebo (all P<0.0001 vs placebo). Body
  11. [11] PMID 35750681 — Phase 1b RCT (n=42, China). IBI362 (mazdutide) 3.0, 4.5, and 6.0 mg subcutaneously for 12 weeks reduced HbA1c, fasting plasma glucose, and post-meal glucose fro
  12. [12] PMID 41260459 — Phase 3 RCT design: mazdutide 6 mg vs semaglutide 1 mg once weekly for 32 weeks (+ 24-week extension) in Chinese adults with T2D and BMI ≥28 kg/m². Primary endp
  13. [13] PMID 41901218 — In a high-fat diet mouse model and in vitro hepatocyte model, mazdutide (100, 200, 400 µg/kg subcutaneously for 4 weeks; 10, 20, 50 nM in vitro) reduced hepatic
  14. [14] PMID 40828048 — In high-fat diet male C57BL/6 mice, subcutaneous mazdutide (every 3 days for 4 weeks) produced greater reduction in MRI-derived hepatic fat fraction (PDFF) than
  15. [15] PMID 42555719 — Tubular GCGR signalling exerts a renoprotective role in diabetic kidney disease (DKD) in mouse models and correlates with kidney function in human DKD samples.
  16. [16] PMID 40479843 — In male db/db mice (T2D model), mazdutide significantly improved cognitive performance and neuronal/brain tissue integrity vs dulaglutide, with multi-omics anal
  17. [17] PMID 42410325 — Meta-analysis of 9 RCTs found mazdutide improved uric acid levels in adults with overweight/obesity and/or T2D, among other metabolic outcomes.
  18. [18] PMID 41030857 — Single case report: 15-year-old male with obesity, T2DM, and hyperuricemia. After 36 weeks of dose-escalated mazdutide (2→4→6 mg subcutaneously once weekly), se
  19. [19] PMID 41804840 — Meta-analysis of 5 RCTs (non-diabetic patients): mazdutide significantly reduced systolic blood pressure (MD -7.68 mmHg), total cholesterol (MD -0.57 mmol/L), a
  20. [20] PMID 38440786 — Meta-analysis of 7 RCTs: mazdutide reduced systolic BP (MD -7.57 mmHg), diastolic BP (MD -2.98 mmHg), total cholesterol (MD -16.82%), triglycerides (MD -43.29%)
  21. [21] PMID 41028652 — in-prose reference
  22. [22] PMID 41478576 — in-prose reference
  23. [23] PMID 41025406 — in-prose reference
  24. [24] PMID 42535526 — in-prose reference
  25. [25] PMID 41710707 — in-prose reference
Dial in your dose in chat →

Related peptides

Melanotan ISynthetic melanocortin peptide analogue (α-MSH analogue); melanocortin receptor agonistMaridebart CafraglutideAntibody-peptide conjugate; bispecific molecule combining a fully human monoclonal anti-hu…Melanotan IISynthetic cyclic heptapeptide; non-selective melanocortin receptor agonist; alpha-melanocy…