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Mazdutide (GLP-1 / glucagon receptor dual agonist)
An investigational once-weekly injectable GLP-1 and glucagon receptor dual agonist (an oxyntomodulin analogue, IBI362/LY3305677) developed mainly in China by Innovent and Eli Lilly for obesity and type 2 diabetes. Honest appraisal: real phase-2 and phase-3 randomized trials show clinically meaningful weight loss (~12-17% at higher doses) and HbA1c reduction, but the evidence is almost entirely single-region (Chinese) and recent. It was approved in China in 2025 — it is NOT FDA-approved and is not available or approved in the West. It is a prescription drug, not a dietary supplement.
Prescription medication — not a dietary supplement
Mazdutide is a prescription (or investigational) drug, not a supplement. It is included here for reference because people research and discuss it (often used off-label) — not as a recommendation. Take it only under a qualified clinician's supervision and only as prescribed; do not source it from grey-market vendors, where identity, purity, and dosing are unverified. The evidence below reflects its clinical trials.
What the evidence says
Most Mazdutide studies are mechanism or observational rather than RCTs that measure a clinical effect — keep findings provisional.
Most evidence is from high-quality meta-analyses and randomised trials published 2021–2026 with a typical study size of 349 participants.
Based on 17 studies · 3 meta-analyses · 11 RCTs · 3,997 total participants
Confidence
High confidenceBy outcome
Moderate score reflects methodologically sound phase-2/3 RCTs and meta-analyses showing large weight loss and HbA1c reductions, tempered by recent, almost entirely single-region (Chinese) data, no FDA approval, and no long-term outcomes.
17 rigorous studies
8 randomized trials · 8 meta-analyses · 6 systematic reviews
Our evidence rating for Mazdutide is accountable to this entire body of rigorous research indexed in PubMed — not a hand-picked subset.
PubMed · as of Jul 2026
19 trials ongoing or recruiting · 17 completed on ClinicalTrials.gov
1 of the completed trials have posted results
Registered trials show research momentum for Mazdutide, not proof of effect — a registration is a plan, and posted results are sponsor-reported, not peer-reviewed. They are never counted toward the evidence rating above.
Browse these trials on ClinicalTrials.govClinicalTrials.gov · as of Aug 2026
Mazdutide (development codes IBI362 / LY3305677; Chinese brand Xinermei) is a once-weekly subcutaneous peptide that activates two receptors at once: the glucagon-like peptide-1 (GLP-1) receptor and the glucagon (GCGR) receptor. It is an analogue of oxyntomodulin, a gut hormone that naturally engages both receptors.
GLP-1 agonism suppresses appetite and slows gastric emptying; adding glucagon agonism is intended to raise energy expenditure and reduce hepatic fat, on top of the GLP-1 weight-loss effect. It is co-developed by Innovent Biologics and Eli Lilly.
In June 2025 it received its first approval — in China — for long-term weight management in adults (BMI >=28, or >=24 with a weight-related comorbidity), and in September 2025 a second China approval for glycemic control in type 2 diabetes.
It is NOT approved by the FDA, EMA, or other Western regulators, and is investigational outside China.
The clinical evidence is genuine but geographically narrow: phase-1b multiple-ascending-dose trials (2021-2022) established tolerability and dose-dependent weight loss; phase-2 trials in Chinese adults with overweight/obesity showed ~6.7-11.3% weight loss at 24 weeks (3-6 mg) and ~12.8% at 9 mg, and a phase-2 T2D trial showed HbA1c reductions of ~1.4-1.7% with weight loss, superior to dulaglutide.
The pivotal phase-3 program (GLORY) reported ~11-14% weight loss at 48 weeks (4/6 mg, GLORY-1) and ~16.7% at 60 weeks (9 mg, GLORY-2) versus placebo, plus phase-3 T2D trials showing HbA1c reductions up to ~2.2% (monotherapy vs placebo) and superiority to dulaglutide.
Beneficial effects on blood pressure and lipids were consistently seen. The most frequent adverse effects are gastrointestinal (nausea, vomiting, diarrhea) — notably common at the 9 mg dose (vomiting ~53%, nausea ~47% in GLORY-2) — mostly mild-to-moderate and concentrated during dose escalation.
Because it also agonizes the glucagon receptor, class-level questions about heart rate and hepatic effects warrant monitoring, and long-term outcome data are not yet available.
This is a prescription drug under investigation in the West, not a supplement; anything sold as 'mazdutide' outside a legitimate Chinese prescription is grey-market material of unverified identity, purity, and dose.
Overall the evidence is moderate: methodologically sound phase-2/3 RCTs, but recent, mostly single-region, and not yet FDA-approved.
Mazdutide is a single oxyntomodulin-analogue peptide that activates both the GLP-1 receptor and the glucagon (GCGR) receptor — the basis for its 'dual agonist' classification, combining GLP-1-driven appetite suppression with glucagon-driven energy expenditure and hepatic effects.
Through GLP-1 agonism it suppresses appetite and slows gastric emptying, reducing food intake — the main driver of the weight loss seen across the GLORY phase-3 program.
Glucagon-receptor agonism is intended to increase energy expenditure and reduce liver fat, an effect proposed to add to GLP-1-driven weight loss — though the glucagon arm also raises class-level monitoring questions (heart rate, hepatic, glucose).
Enhances glucose-dependent insulin secretion via GLP-1 agonism, lowering HbA1c and fasting glucose in type 2 diabetes trials, with weight loss as a co-benefit.
How Mazdutide works — from molecular targets to health outcomes. Click an edge to see supporting research.This visualization is in beta — pathways are being refined and expanded.
Investigational and not approved — there is no legitimate, quality-assured supply outside a Chinese prescription. Do not use grey-market material.
Use with caution or avoid; monitor for pancreatitis symptoms.
Hypoglycemia risk — concomitant doses may need reduction under medical supervision.
Contraindicated — not studied in pregnancy and weight loss is not recommended during pregnancy.
Additive glucose-lowering raises hypoglycemia risk; concomitant doses may need reduction under medical supervision.
Delayed gastric emptying can alter the absorption of co-administered oral drugs; most relevant for narrow-therapeutic-index agents and oral contraceptives.
Tip: Slow dose escalation; smaller meals; usually eases after titration
Tip: Slower escalation; especially frequent at the 9 mg dose
Tip: Hydration; slower escalation
Tip: Expected effect; ensure adequate protein intake
Tip: Monitor; the glucagon arm warrants attention to heart rate — report palpitations
Tip: Stop and seek care for severe persistent abdominal pain; avoid with a pancreatitis history
Mazdutide has an evidence score of 5/10 — moderate evidence based on 16 indexed studies, including 2 meta-analyses. An investigational once-weekly injectable GLP-1 and glucagon receptor dual agonist (an oxyntomodulin analogue, IBI362/LY3305677) developed mainly in China by Innovent and Eli Lilly for obesity and type 2 diabetes. Honest appraisal: real phase-2 and phase-3 randomized trials show clinically meaningful weight loss (~12-17% at higher doses) and HbA1c reduction, but the evidence is almost entirely single-region (Chinese) and recent. It was approved in China in 2025 — it is NOT FDA-approved and is not available or approved in the West. It is a prescription drug, not a dietary supplement. Representative study: PMID 41804840.
The commonly studied dose of Mazdutide is Investigational / China-only dosing: once-weekly subcutaneous injection, dose-escalated over several weeks. Trial maintenance doses studied were 4 mg, 6 mg, and 9 mg once weekly (lower doses used during titration to limit GI effects). There is no FDA-approved regimen.. Individual needs vary — start at the lower end of the range and adjust based on how you respond.
Timing is flexible for Mazdutide — consistent daily use matters more than the time of day. Administered once weekly on the same day, with or without food.
Mazdutide should be used with caution — talk to a healthcare provider before taking it. The most commonly reported side effects are nausea, vomiting, diarrhea. Use caution if any of these apply to you: Pregnancy and breastfeeding; Personal or family history of medullary thyroid carcinoma or MEN2 (class-level precaution for GLP-1-based agents); History of pancreatitis (use with caution / avoid).
Semaglutide
Mostly mechanism / observationalAn FDA-approved GLP-1 receptor agonist (Ozempic/Rybelsus for type 2 diabetes, Wegovy for chronic weight management) with genuinely strong, large-RCT evidence for glycemic control and substantial weight loss, plus a cardiovascular-outcomes benefit. Honest appraisal: this is a real prescription medicine with real efficacy AND real risks — a boxed warning for thyroid C-cell tumors, pancreatitis and gallbladder risk, very common GI side effects, and growing concern about grey-market/compounded versions. It is included here for reference only, not as a supplement and not auto-recommended.
Tirzepatide
Mostly mechanism / observationalAn FDA-approved prescription medication (Mounjaro for type 2 diabetes, Zepbound for obesity and obstructive sleep apnea), not a dietary supplement. Honest appraisal: in head-to-head phase-3 trials it is the most effective approved weight-loss drug to date — up to ~21% body-weight loss over 72 weeks and superior to semaglutide — but it is a real medicine with real risks: a boxed warning for thyroid C-cell tumors, common GI side effects, and pancreatitis/gallbladder signals. Do not source or use it outside a prescription.
Liraglutide
Mostly mechanism / observationalAn FDA-approved, once-daily GLP-1 receptor agonist (Victoza for type 2 diabetes, Saxenda for chronic weight management). Honest appraisal: a real prescription medicine with genuinely strong large-RCT evidence for glycemic control and moderate weight loss, plus a cardiovascular-outcomes benefit (LEADER). It also carries real risks — a boxed warning for thyroid C-cell tumors, pancreatitis and gallbladder risk, very common GI side effects, and lean-mass loss with weight loss. Included here for reference only; it is NOT a supplement and is not auto-recommended.
Orforglipron
Mostly mechanism / observationalAn investigational ORAL, non-peptide small-molecule GLP-1 receptor agonist for obesity and type 2 diabetes — the headline is the convenience of a once-daily pill (no injection, no cold chain, no food/water restrictions) delivering GLP-1-class glycemic and weight benefit. Honest appraisal: the phase-2 data are strong and the first phase-3 read-outs (ATTAIN/ACHIEVE) are promising, but it is INVESTIGATIONAL and not yet approved as a general weight-loss medicine, has the full GLP-1-class side-effect burden (very common dose-dependent nausea/vomiting/diarrhea, higher discontinuation than injectables in some comparisons), and the expected thyroid C-cell class warning and long-term outcomes are unsettled. It is NOT a dietary supplement; listed here for reference only.
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Reviewed by Dr. Baher Al Hakim · Last reviewed June 2026 · evidence from 17 studies · how we score · editorial policy
This information is for educational purposes only. It is not a substitute for professional medical advice. Always consult a qualified healthcare provider before starting, stopping, or changing any supplement or medication.
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