Mazdutide
InvestigationalA dual GLP-1 and glucagon receptor agonist developed by Innovent/Eli Lilly. NMPA approved in China (2025) for obesity. The GLORY-1 trial showed 14.0% weight loss at 48 weeks with the 6mg dose. The DREAMS-3 head-to-head trial vs semaglutide for combined diabetes + obesity outcomes is ongoing, with results not yet published.
IBI362 · LY3305677 · Xinermei
14 human studies
- Preclinical
- 7%
- Clinical
- 93%
Based on 15 cited sources
Historical editorial rating. No completed numerical assessment is established by this record. These scores are not formal GRADE assessments, measured treatment effects, or safety ratings.
- Recorded primary indication:
- Obesity / chronic weight management
- Compound / formulation, population, comparator, outcome and timepoint for the numeric assessment:
- Not recorded in this score record
Community usage signal; not evidence of efficacy or safety. Provenance is not established by this score.
based on clinical studies · high confidence
Clinical-study effect summary; outcomes depend on population and endpoint. This score is not a probability of benefit or a safety rating.
Research Depth 90: highest tier is meta-analysis of multiple independent double-blind placebo-controlled Phase 3 RCTs (1A 35) — GLORY-1 N=610 (40421736), plus a Phase 2 program (37943529 N=249; 38092790 N=248); best studies are low-RoB large RCTs with supporting reviews (1B 22), total human N well over 1,000 (1C 14), direct obese/T2D population + SC route + weight and HbA1c outcomes (1D 14), and a modest preclinical base (1E 5). Mechanism 80: named GLP-1R + GCGR targets with binding and functional agonist confirmation (2A 30), receptor-pathway-to-effect largely mapped (2B 24), multi-dose human + in-vivo dose-response (2C 16), confirmed in vivo (40479843 db/db mice) and in humans (2D 10). Plausibility 88: full mechanism->surrogate (weight/HbA1c)->clinical-outcome chain proven in RCTs (3A 34), fully coherent with incretin/glucagon biology (3B 24), multiple same-class agonists reproduce the effect (3C 18), tightly scoped metabolic claims (3D 12). Global Coverage 54: replicated across many Chinese hospital groups but primary trials are almost entirely China/Innovent-led, limiting independent cross-country replication (4A 16, 4B 10); 20+ diverse studies (4C 18); single-regulator NMPA approval (4D 10). Community Experience 16: dossier records negligible documented real-world use; newly approved 2025 so short track record and no consistent user-report corpus (5A 4, 5B 6, 5C 0, 5D 6 for documented trial-level GI tolerability, not a safety claim). Effectiveness basis clinical (high): GLORY-1 6mg -14.0% body weight vs ~0% placebo at 48 weeks, far exceeding the ~5% obesity MCID with hard patient-relevant weight and cardiometabolic outcomes; superior to dulaglutide on HbA1c/weight, though head-to-head vs semaglutide (DREAMS-3, 41260459) is pending and indirect comparisons place it below retatrutide.
Mazdutide is a dual GLP-1 and glucagon receptor agonist with robust Phase 3 clinical trial data. Its mechanisms are well-characterized in human studies.
How It Works (Simplified)
GLP-1 receptor activation in the brain increases satiety signals, reducing hunger and food intake similar to semaglutide.
Glucagon receptor activation directly stimulates hepatic fatty acid oxidation, burning fat stored in the liver.
Glucose-dependent insulin secretion improves blood sugar control without causing hypoglycemia when blood sugar is normal.
Glucagon increases metabolic rate and calorie burning, contributing to weight loss beyond appetite reduction alone.
Key Research: Ji L et al. (NEJM 2025) demonstrated 14.0% weight loss at 48 weeks with the 6mg dose, alongside beneficial effects on all prespecified cardiometabolic measures, in the GLORY-1 trial. PMID:40421736
Important Limitations
- Currently only approved in China (NMPA); not yet FDA approved
- Long-term safety data beyond 48 weeks is limited
- Head-to-head data vs tirzepatide not yet available
- Optimal patient selection criteria still being refined
- GI tolerability requires careful dose titration
Initial dose titration period. Nausea and GI effects most common during this phase. Early appetite suppression and reduced food intake typically begin within days of first dose.
PMID:40421736Continued dose escalation to target dose. Steady weight loss averaging 1-2% body weight per month. Blood glucose improvements measurable. GI side effects typically diminish.
PMID:40421736Maintenance dosing established. Weight loss continues at consistent rate. HbA1c improvements reach clinically significant levels and cardiometabolic measures continue to improve.
PMID:40421736Peak efficacy period. GLORY-1 showed 14.0% total body weight loss at 48 weeks with the 6mg dose. Sustained glycemic control and improvements across cardiometabolic measures.
PMID:40421736Research-based observations
This timeline reflects observations from published clinical and preclinical studies. Individual responses may vary significantly. This is not a guarantee of effects or a dosing schedule. Consult qualified healthcare providers for personalized guidance.
BPC-157
CautionBoth affect GI function. Mazdutide slows gastric emptying while BPC-157 is gastroprotective. Monitor GI symptoms if combined; interaction data unavailable.
Semaglutide
AvoidBoth are GLP-1 receptor agonists. Combining would duplicate mechanisms and increase risk of severe GI adverse effects and hypoglycemia. No clinical rationale for combination.
Tirzepatide
AvoidBoth target GLP-1 receptors with overlapping mechanisms. Combining incretin therapies is contraindicated due to additive effects and safety concerns.
Survodutide
AvoidBoth are dual GLP-1/glucagon receptor agonists with identical mechanisms. Combination would be redundant and potentially dangerous.
Research Note: Interaction data is based on published literature, mechanistic understanding, and theoretical considerations. Most peptide combinations lack direct clinical study. This information is for educational purposes only and does not constitute medical advice. Always consult qualified healthcare providers.
Key Studies Cited
Full reference list available on request. All citations link to PubMed for verification.
This dossier synthesizes available evidence from peer-reviewed literature, regulatory documents, and clinical trial registries. Evidence strength ratings follow a modified GRADE approach.
For complete methodology details, see our Methodology page.
Important Disclaimer
This dossier is for educational purposes only and does not constitute medical advice. Always consult a qualified healthcare provider before making health decisions.
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Compared With
11 comparisonsConditions Studied
3 entries- Mazdutide for Obesity Mazdutide has robust Phase 3 evidence for obesity treatment. The GLORY-1 trial (N=610) demonstrated 14.0% weight loss at 48 weeks…
- Mazdutide for Type 2 Diabetes A phase 2 trial showed clinically meaningful glycemic control, with HbA1c reduced 1.41-1.67% vs placebo in Chinese patients with t…
- Mazdutide for Non-Alcoholic Fatty Liver Disease Mazdutide's glucagon receptor activation is proposed to reduce hepatic fat via increased fatty acid oxidation. GLORY-1 reported be…