Mazdutide
The world's first approved dual GLP-1/glucagon receptor agonist, developed by Innovent Biologics (China). Approved in China for obesity and type 2 diabetes. Phase 3 trials showed up to 20.1% weight loss.
What is Mazdutide?
Mazdutide (IBI362/LY3305677, brand name Xinermei) is a synthetic oxyntomodulin analog with a C18 fatty acid side chain enabling once-weekly subcutaneous dosing. It is a dual agonist of both GLP-1 and glucagon receptors — the same mechanism as survodutide but developed independently by Innovent Biologics in China, with Eli Lilly holding rights outside China. In June 2025, it became the world's first approved dual GCG/GLP-1 receptor agonist when China's NMPA approved it for weight management, followed by type 2 diabetes approval in September 2025. Phase 3 trials showed up to 20.1% weight loss at 9 mg (GLORY-2) and the DREAMS-3 head-to-head trial against semaglutide is underway (only the protocol and baseline paper are currently published on PubMed; full outcomes data have been reported by the sponsor but not yet in a peer-reviewed results paper). It is not FDA or EMA approved and no US filing has been announced.
What Mazdutide Is Investigated For
Mazdutide is studied for obesity and type 2 diabetes as a once-weekly dual GLP-1/glucagon receptor agonist — a mechanistic inversion of tirzepatide's GLP-1/GIP dual agonism, built on oxyntomodulin biology with added glucagon-mediated energy expenditure and hepatic fat oxidation. The strongest evidence is the Phase 3 GLORY and DREAMS programs: GLORY-2 showed 20.1% weight loss at 9 mg over 60 weeks, GLORY-1 showed 14.0% at 6 mg over 48 weeks; the DREAMS-3 head-to-head trial against semaglutide has published only its protocol and baseline paper on PubMed — sponsor-reported outcomes favor mazdutide, but peer-reviewed results are pending. In June 2025, it became the world's first approved dual GCG/GLP-1 receptor agonist when China's NMPA approved it as Xinermei, with type 2 diabetes approval following in September 2025. The key caveats: mazdutide is not FDA or EMA approved and Eli Lilly (which holds ex-China rights) has not announced a US filing — likely due to tirzepatide portfolio overlap. No completed cardiovascular outcomes trial, no dedicated MASH/MASLD trial despite the glucagon-agonism rationale, pivotal trials enrolled exclusively Chinese participants, and grey-market 'mazdutide' sold outside China cannot be assumed to match the Innovent product on sequence, purity, or potency.
History & Discovery
Mazdutide was discovered and developed by Eli Lilly under the code LY3305677 as part of Lilly's broader exploration of oxyntomodulin-derived dual GLP-1/glucagon receptor agonists. In 2019, Lilly out-licensed Greater China rights (mainland China, Hong Kong, Macau, Taiwan) to Innovent Biologics, which advanced the molecule under the code IBI362 through a comprehensive Chinese clinical program. The GLORY (obesity) and DREAMS (type 2 diabetes) Phase 3 trial families were run in Chinese populations and read out across 2024 and 2025, with GLORY-2 reaching 20.1% mean weight loss at the 9 mg dose. China's NMPA approved mazdutide for chronic weight management in June 2025 — the first regulatory approval anywhere of a dual GLP-1/glucagon agonist — and added a type 2 diabetes indication in September 2025 under the brand name Xinermei. Lilly retains rights outside Greater China but has not announced a US or EU regulatory filing, in part because tirzepatide already occupies that space in the Lilly portfolio.
How It Works
Mazdutide activates two receptors: GLP-1 (which reduces appetite and improves blood sugar) and glucagon (which increases energy expenditure and promotes fat burning in the liver). The combination means you eat less AND burn more — a dual approach that neither receptor alone achieves as effectively.
Mazdutide is a synthetic analog of oxyntomodulin, a naturally occurring gut hormone that activates both GLP-1R and GCGR. A C18 fatty acid side chain extends the half-life to enable once-weekly dosing. GLP-1R activation in the hypothalamus suppresses appetite, in the pancreas enhances glucose-dependent insulin secretion, and in the GI tract slows gastric emptying. GCGR activation in hepatocytes increases fatty acid oxidation and energy expenditure while promoting glycogenolysis. Phase 3 results: GLORY-1 (610 patients, 48 weeks) showed 14.0% weight loss at 6 mg with 49.5% achieving at least 15%. GLORY-2 (462 patients, 60 weeks) showed 20.1% at 9 mg. DREAMS-1 (320 patients, 24 weeks) showed HbA1c reduction of 2.02% at 6 mg. DREAMS-3 (n≈349, 32-week head-to-head vs semaglutide) has published its protocol and baseline data on PubMed; peer-reviewed outcomes are not yet indexed.
Evidence Snapshot
Human Clinical Evidence
Strong. Multiple Phase 3 RCTs published in NEJM and Nature. GLORY-1 (n=610, obesity): 14.0% weight loss at 6 mg. GLORY-2 (n=462, obesity): 20.1% at 9 mg. DREAMS-1 (n=320, T2D): HbA1c -2.02%. DREAMS-2 (n=731, T2D): superior to dulaglutide. DREAMS-3 (n=349, T2D): superior to semaglutide on combined endpoint. Approved by China's NMPA for both obesity and T2D.
Animal / Preclinical
Supportive. Oxyntomodulin biology and dual GCG/GLP-1 agonism well-established from preclinical pharmacology. Clinical data now the primary evidence base.
Mechanistic Rationale
Strong. Dual GCG/GLP-1 agonism is well-validated by both mazdutide and survodutide clinical programs. The addition of glucagon receptor activation to GLP-1 provides mechanistically distinct energy expenditure and hepatic fat oxidation benefits.
Research Gaps & Open Questions
What the current literature has not yet settled about Mazdutide:
- 01Cardiovascular outcomes — no completed CVOT has been published for mazdutide; whether it produces MACE reduction comparable to semaglutide (SELECT) and tirzepatide (SURPASS-CVOT) is not established.
- 02Long-term safety beyond Phase 3 trial durations — pancreatitis, gallbladder disease, diabetic retinopathy progression, and rare oncologic signals require multi-year exposure data.
- 03Generalizability beyond Chinese populations — pivotal Phase 3 trials enrolled exclusively Chinese participants, and the extent to which efficacy and safety findings translate to other populations has not been studied.
- 04Hepatic-specific outcomes — given the glucagon component's known effects on hepatic fat oxidation, dedicated MASH/MASLD trials would be informative but have not been published.
- 05Direct head-to-head comparison with tirzepatide and retatrutide.
- 06Body-composition effects (lean mass loss vs. fat-mass loss) at the 9 mg high dose are not yet published in detail.
Forms & Administration
Mazdutide is administered as a once-weekly subcutaneous injection. Approved doses in China: 3 mg, 4.5 mg, and 6 mg for obesity; up to 6 mg for T2D. Phase 3 trials tested up to 9 mg. Dose escalation over several weeks is standard to minimize GI side effects. Currently only available in China as Xinermei.
Dosing & Protocols
The ranges below reflect protocols commonly discussed in the literature and by clinicians — not a prescription. Actual dosing for any individual should be determined by a qualified healthcare provider who knows the patient.
Typical Range
Per the Chinese label for chronic weight management, mazdutide is dosed at 3 mg, 4.5 mg, or 6 mg once weekly subcutaneously after a stepwise titration. For type 2 diabetes, the approved range tops out at 6 mg weekly. Phase 3 GLORY-2 also tested a 9 mg maintenance dose for obesity, which produced the 20.1% mean weight loss figure but is not currently in the approved label.
Frequency
Once weekly subcutaneous injection on the same day each week, with or without regard to meals. The C18 fatty-acid acylation enables a half-life consistent with weekly dosing.
Timing Considerations
No specific timing requirements: can be administered at any time of day, with or without food, and is not tied to exercise timing. Consistency matters more than the specific clock — dose at roughly the same time each day (or same day each week, for weekly protocols) to keep exposure steady.
Cycle Length
Mazdutide is intended for chronic, indefinite use in both obesity and type 2 diabetes. It is not a cycled or short-course intervention. Discontinuation kinetics have not been characterized in the published Chinese trials, but based on the broader incretin class, substantial weight regain within 6–12 months of stopping should be expected.
Protocol Notes
Outside mainland China, mazdutide is not commercially available through any legitimate channel. Lilly has not announced a US or EU filing, and no FDA-approved generic, compounded, or imported version exists in the United States. Material sold under the mazdutide name on grey-market sites, including 'research-chemical' suppliers, is not the licensed Innovent product, has not been bioequivalence-tested, and may differ in sequence, salt form, purity, or potency. The Chinese-label dosing schedule is the only formally validated regimen.
Mazdutide is not approved by the FDA or EMA. The dosing described above reflects the Chinese label and trial protocols, not US prescribing guidance. Use outside an authorized clinical or licensed prescribing context is unsupervised and unregulated.
Timeline of Effects
Onset
Reduced appetite and early weight loss are typically reported within the first 2–4 weeks of dosing, consistent with the GLP-1 mechanism. Glycemic improvements in the DREAMS trials emerged within the first month and continued to deepen through the titration period.
Peak Effect
In GLORY-2 (9 mg, 60 weeks), mean weight loss reached approximately 20.1% by trial end, with the curve still trending downward at study completion — suggesting peak effect may extend beyond 60 weeks. In GLORY-1 (6 mg, 48 weeks), mean weight loss plateaued closer to 14%. HbA1c reductions in DREAMS-1 reached approximately -2.0 percentage points at 6 mg by month 6.
After Discontinuation
Discontinuation kinetics have not been formally reported in the published GLORY/DREAMS data. Based on the GLP-1/glucagon class and parallels to STEP-1 follow-up data for semaglutide, the working assumption is that two-thirds or more of lost weight is regained within 12 months of cessation, with HbA1c, blood pressure, and lipid markers also reverting toward baseline.
Common Questions
Who Mazdutide Is NOT For
- •Personal or family history of medullary thyroid carcinoma (MTC) — boxed warning class effect across GLP-1 receptor agonists based on rodent C-cell tumor findings.
- •Multiple Endocrine Neoplasia syndrome type 2 (MEN2) — same mechanistic concern as MTC.
- •Active pancreatitis or history of recurrent pancreatitis — rare class-level pancreatitis signals support precautionary avoidance.
- •Pregnancy — no human pregnancy safety data; the long half-life and developmental concerns of the incretin class make use during pregnancy or for at least two months before a planned pregnancy inadvisable.
- •Breastfeeding — no human lactation data.
- •Severe gastroparesis or other significant GI motility disorders — both GLP-1 and glucagon receptor agonism affect GI physiology.
- •Insulinoma or other conditions of inappropriate hyperinsulinemia — glucagon agonism can complicate already dysregulated counter-regulatory physiology.
Drug & Supplement Interactions
The two clinically important interaction domains parallel those of semaglutide and other GLP-1 agonists. First, hypoglycemia risk increases when mazdutide is combined with insulin or insulin secretagogues (sulfonylureas, meglitinides), and downward titration of those concomitant agents at mazdutide initiation and each escalation step is the standard mitigation. Second, the slowed gastric emptying induced by GLP-1 receptor activation alters the absorption rate and peak concentration of orally administered drugs, with particular attention warranted for narrow-therapeutic-index agents (warfarin, levothyroxine, oral contraceptives, antiepileptics). The added glucagon receptor agonism introduces an additional consideration: transient elevations in hepatic glucose output and lipolysis could theoretically interact with chronic medications affecting hepatic metabolism, though this has not been systematically characterized in the published trial data. Patients prescribed mazdutide in China should disclose all concurrent medications to their prescriber.
Safety Profile
Common Side Effects
Cautions
- • Approved only in China — not FDA or EMA approved
- • GI side effects are dose-dependent; slower titration improves tolerability
- • Glucagon receptor activation may raise hepatic glucose output transiently
- • Long-term safety data beyond clinical trial durations is limited
What We Don't Know
Cardiovascular outcomes data is not yet available. Whether the glucagon component confers additional liver or metabolic benefits beyond GLP-1 alone in long-term use is still being studied. Western market safety data and regulatory review have not occurred.
Legal Status
United States
Mazdutide is not FDA-approved and has no announced US regulatory filing. Lilly holds the ex-Greater China rights but has not signaled a Western development path, likely due to portfolio overlap with tirzepatide. It is not legally available through US compounding pharmacies, telehealth providers, or any other domestic channel. Personal importation from China is not legal under FDA rules and is enforced inconsistently.
International
Approved in mainland China by the NMPA for chronic weight management (June 2025) and type 2 diabetes (September 2025) as Xinermei. Not approved by the EMA, UK MHRA, Health Canada, Australia's TGA, or any other major regulator outside China. No public timeline exists for ex-China filings.
Sports & Competition
Not currently listed by name on the WADA Prohibited List. As an approved peptide hormone in at least one jurisdiction, mazdutide falls under WADA's S2 category (peptide hormones, growth factors, related substances and mimetics), which prohibits use in and out of competition for athletes subject to the WADA code. It also falls under S0 in jurisdictions where it is not yet approved.
Regulatory status changes over time. Verify current local rules with a qualified professional.
Myths & Misconceptions
Myth
Mazdutide is FDA-approved or available in the US.
Reality
It is approved only in mainland China. Lilly holds ex-China rights but has not filed in the US or EU, and there is no legal pathway for compounding pharmacies, telehealth platforms, or grey-market suppliers to provide mazdutide domestically.
Myth
Because it adds glucagon agonism to GLP-1, mazdutide raises blood sugar and is dangerous for diabetics.
Reality
The DREAMS Phase 3 program in type 2 diabetes patients showed substantial HbA1c reductions, including superiority over semaglutide on a combined glycemic-and-weight endpoint. The GLP-1 component dominates net glycemic effect; the glucagon component contributes hepatic fat oxidation and energy expenditure benefits without producing net hyperglycemia at therapeutic doses.
Myth
Mazdutide and survodutide are effectively the same drug.
Reality
Both are dual GLP-1/glucagon receptor agonists derived from oxyntomodulin biology, but they are distinct molecules with different sequences, receptor potencies, and developers (Innovent/Lilly vs. Boehringer Ingelheim). They have not been compared head-to-head, and their development trajectories differ — mazdutide is approved in China, survodutide is in global Phase 3.
Myth
Grey-market 'mazdutide' sold by research-chemical suppliers is the same as Xinermei, just cheaper.
Reality
Xinermei is the licensed Innovent product manufactured under regulated pharmaceutical conditions. Material sold under the mazdutide name outside China cannot be assumed to share sequence, salt form, purity, or potency with the approved drug, and is not authorized for human use anywhere.
Published Research
7 studiesMazdutide versus dulaglutide for type 2 diabetes in China: a randomized, double-blind, active-controlled Phase 3 trial (DREAMS-2).
Mazdutide for type 2 diabetes: a randomized, double-blind, placebo-controlled Phase 3 trial (DREAMS-1).
DREAMS-1 — the phase 3 T2D trial supporting mazdutide's September 2025 NMPA approval for type 2 diabetes, alongside the DREAMS-2 and DREAMS-3 active-comparator arms.
Mazdutide versus Semaglutide for the treatment of type 2 diabetes and obesity: Rationale, design and baseline data of DREAMS-3 phase 3 trial.
Mazdutide: First Approval.
Mazdutide, a dual glucagon-like peptide 1 and glucagon receptor agonist for the treatment of obesity in Chinese adults: a multicentre, randomised, double-blind, parallel-controlled, dose-finding, phase 3 trial (GLORY-1).
GLORY-1 — the pivotal phase 3 obesity trial that supported China's NMPA approval of mazdutide in June 2025, the first regulatory approval anywhere of a dual GLP-1/glucagon receptor agonist.
GLP-1/glucagon receptor dual agonists for obesity and type 2 diabetes: a systematic review and meta-analysis.
Safety, tolerability, and pharmacokinetics of mazdutide (IBI362), a dual GLP-1/glucagon receptor agonist: Phase 1b study.
Quick Facts
- Class
- Incretin Mimetic
- Tier
- B
- Evidence
- Moderate
- Safety
- Limited Data
- Updated
- Apr 2026
- Citations
- 7PubMed
Also known as
Tags
Peptide Families
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Evidence Score
Clinical Trials
View Clinical TrialsLinks to ClinicalTrials.gov for reference. Listing does not imply endorsement.