Mazdutide

IBI362 · LY3305677 · Innovent / Eli Lilly · GLP-1/Glucagon Dual

"The first glucagon/GLP-1 dual agonist approved anywhere — an oxyntomodulin analogue cleared in China in 2025 for obesity and type 2 diabetes. Where pure GLP-1 drugs suppress appetite, mazdutide's glucagon arm also raises energy expenditure and clears liver fat. Still investigational in the UK."

Type

GLP-1 / glucagon dual agonist · OXM analogue

Origin

Innovent + Eli Lilly · GLORY / DREAMS programme

Status

UK: legal to buy or possess — no UK marketing authorisation (investigational here) · WADA: not specifically listed · China NMPA: approved 2025 for obesity & T2D · US FDA / MHRA: not approved

Phase 3 weight loss

~14.8% at 6 mg (GLORY-1) · up to ~20.1% at 9 mg (GLORY-2)

Protocol summary

Approved dose

4–6 mg weekly SubQ (9 mg studied)

Mechanism

GLP-1 / glucagon dual (OXM)

Status

China-approved · pre-approval in UK

Approved (China)

4 mg or 6 mg once-weekly SubQ, titrated up over several weeks

China NMPA label; no UK licence

Community-reported

Titration extrapolated from trial schedules; 9 mg used for higher baseline weight

Unlicensed in UK; purity/authenticity unverifiable

How we read the evidence

First-in-class GLP-1/glucagon dual agonist · approved in China (2025) on Phase 3 data · ~14.8% weight loss at 6 mg over 48 weeks (GLORY-1, NEJM) · up to ~20.1% at 9 mg (GLORY-2) · not yet approved in the UK/US

Animal & preclinical

Mazdutide (IBI362 / LY3305677 / OXM3) is a mammalian oxyntomodulin (OXM) analogue with a fatty-acid side chain for once-weekly dosing. Oxyntomodulin is a natural gut hormone released after eating that activates both the GLP-1 receptor and the glucagon receptor — so unlike engineered multi-agonists, mazdutide is modelled on an endogenous dual-acting peptide. Preclinically, the glucagon arm increases energy expenditure and drives hepatic fat oxidation, complementing GLP-1-mediated appetite suppression and glucose-dependent insulin secretion. Eli Lilly licensed the molecule to Innovent Biologics for development in China.

Community & clinical practice

Mazdutide is an approved medicine in China but unlicensed elsewhere. In China it is prescribed for chronic weight management (BMI ≥28, or ≥24 with weight-related comorbidities) and for type 2 diabetes. Outside China there is no marketing authorisation, and research-peptide vendors supplying "mazdutide" cannot be verified for identity or purity. Community protocols extrapolate the trial titration (a low starting dose escalating to 4–6 mg, or 9 mg for higher baseline weight). Pep IQ does not endorse unsupervised use — this is a potent metabolic drug, and self-administration of an unlicensed version carries real authenticity and safety risk.

Human trial data

Large, published Phase 3 base. GLORY-1 (Phase 3, >600 Chinese adults, NEJM, May 2025): at 48 weeks, mean weight loss of ~12% (4 mg) and ~14.8% (6 mg) vs 0.5% placebo; roughly 74% (4 mg) and 83% (6 mg) lost ≥5% of body weight, and 37% / 50.6% lost ≥15%. Liver fat fell 65.85% (4 mg) and 80.24% (6 mg) in participants with ≥10% baseline liver fat. GLORY-2 (9 mg) reported up to ~20.1% weight loss with continued reduction through 60 weeks. DREAMS-1 and DREAMS-2 (Phase 3, type 2 diabetes, published in Nature, 2025) showed glycaemic control as monotherapy and as add-on therapy. Innovent reports seven Phase 3 studies conducted, with the first five meeting their primary endpoints.

Regulatory status

Approved in China only. China's NMPA approved mazdutide for weight management (June 2025) and glycaemic control (September 2025) — the world's first approved glucagon/GLP-1 dual agonist. It is not approved by the FDA, MHRA, or EMA. In the UK it has no marketing authorisation: it is not a controlled drug, so possession is not illegal, but it is an unlicensed/investigational compound here and not available as a licensed medicine. WADA does not list mazdutide specifically; the GLP-1 class is under growing scrutiny.

Convergence

Mazdutide is one of the more mature compounds in this section: a published Phase 3 programme, a major-journal evidence base, and a genuine first-in-class regulatory approval — albeit in a single jurisdiction. The oxyntomodulin design is elegant, and the liver-fat and weight-loss data are strong. But it is not approved in the UK, the long-term and cardiovascular outcome data are still maturing, and any UK supply is unlicensed and unverifiable. Pep IQ flags this honestly: the science and the China approval are real, but until UK/Western approval lands, mazdutide is investigational here — members interested in it should track the trial and approval timeline rather than seek grey-market supply.

Origin & Background

An old gut hormone, re-engineered

Mazdutide began as OXM3 — a synthetic analogue of oxyntomodulin, a naturally occurring gut hormone released after eating that activates both the GLP-1 receptor and the glucagon receptor at once. Rather than bolting two synthetic agonists together, mazdutide is modelled on a peptide the body already uses for dual signalling. Eli Lilly licensed the molecule to Innovent Biologics for development in China, where obesity and type 2 diabetes rates have risen sharply.

The clinical programme is named GLORY (obesity) and DREAMS (diabetes). GLORY-1, the pivotal Phase 3 obesity trial in over 600 Chinese adults, was published in the New England Journal of Medicine in May 2025. On the strength of that data, China's NMPA approved mazdutide for chronic weight management in June 2025 and for glycaemic control in type 2 diabetes in September 2025 — making it the first glucagon/GLP-1 dual agonist approved anywhere in the world.

GLORY-2 then tested a higher 9 mg dose for people with higher baseline weight, reporting up to roughly 20.1% weight loss with no plateau through 60 weeks. Two Phase 3 diabetes trials (DREAMS-1, DREAMS-2) were published back-to-back in Nature in late 2025.

Why the glucagon arm matters: Pure GLP-1 drugs work mainly by suppressing appetite and slowing gastric emptying. Adding glucagon-receptor agonism does something different — it increases energy expenditure and pushes the liver to oxidise fat. That is the rationale for the dramatic liver-fat reductions seen in GLORY-1, and for the idea that a dual agonist can drive weight loss through more than appetite alone. The trade-off is that glucagon can raise glucose and heart rate, which is why dose and receptor balance matter.

Science & Mechanism

Two receptors, one natural template

Mechanism of Action

GLP-1R activation: Central appetite suppression, delayed gastric emptying, and glucose-dependent insulin secretion — the same foundational mechanism as semaglutide and tirzepatide.

Glucagon receptor (GCGR) activation: Increases energy expenditure and drives hepatic fat oxidation, reducing liver fat substantially. This is the thermogenic, liver-directed component that pure GLP-1 agonists lack.

Oxyntomodulin template: Mazdutide is an OXM analogue — based on an endogenous hormone that naturally hits both receptors, rather than an artificial fusion. The balance between the two arms is tuned to gain glucagon's metabolic benefits without provoking problematic rises in blood glucose.

Extended half-life: A fatty-acid side chain enables albumin binding and a long half-life, allowing once-weekly subcutaneous dosing, as with other modern incretin drugs.

In GLORY-1, the 6 mg dose produced ~14.8% mean weight loss at 48 weeks against 0.5% for placebo, with roughly half of participants losing at least 15% of their body weight. The liver-fat signal was striking: about an 80% reduction at 6 mg in those with significant baseline liver fat — a result that has prompted ongoing study in metabolic dysfunction-associated steatohepatitis (MASH).

The higher 9 mg dose in GLORY-2 pushed mean weight loss to around 20%, and the diabetes trials showed meaningful glycaemic control both alone and added to oral therapy. Cardiovascular outcome and longer-term safety data are still accumulating.

Benefits & Evidence

What the data shows

⚖️

Weight loss

GLORY-1 (Phase 3, NEJM 2025): ~12% at 4 mg and ~14.8% at 6 mg over 48 weeks vs 0.5% placebo; ~83% lost ≥5% and ~50% lost ≥15% at 6 mg. GLORY-2: up to ~20.1% at 9 mg, still falling at 60 weeks.

● Strong — Phase 3 GLORY-1 / GLORY-2

🫁

Liver fat reduction

In GLORY-1 participants with ≥10% baseline liver fat, content fell 65.85% (4 mg) and 80.24% (6 mg) at 48 weeks — driven by the glucagon arm's effect on hepatic fat oxidation. Now under study for MASH.

● Strong — Phase 3 substudy

🩸

Glycaemic control (T2D)

DREAMS-1 and DREAMS-2 (Phase 3, Nature 2025) showed mazdutide improved glycaemic control as monotherapy and as add-on to oral agents in Chinese adults with type 2 diabetes. Approved by China's NMPA for this indication.

● Strong — Phase 3 RCT

🫀

Cardiometabolic markers

Phase 2 and Phase 3 reports describe improvements in waist circumference, blood lipids, blood pressure, uric acid and liver enzymes alongside weight loss. Dedicated cardiovascular outcome data is not yet mature.

● Moderate — risk factors · outcomes pending

🏷️

First-in-class approval

The only glucagon/GLP-1 dual agonist approved anywhere — China NMPA, 2025, for both obesity and type 2 diabetes. A genuine regulatory milestone, though limited to one jurisdiction so far.

● Moderate — approved in China only

Things to know

Risks & considerations

Moderate

GI side effects — nausea, diarrhoea, vomiting, constipation. Dose-related, mainly during dose escalation, as with all GLP-1 drugs.

Moderate

Glucagon-related effects — the glucagon arm can increase heart rate and, in principle, hepatic glucose output; trials showed net glycaemic improvement, but this is why dosing is titrated and balanced.

Moderate

Muscle mass loss — as with all potent weight-loss drugs, a portion of weight lost without resistance training and adequate protein can be lean mass.

Serious

Class contraindications — GLP-1-class cautions apply: personal/family history of medullary thyroid carcinoma or MEN-2, pancreatitis risk, and pregnancy. Approved-label use in China is under medical supervision.

⚠ Key Warnings

Mazdutide is approved only in China. It is not licensed in the UK, US, or EU — any UK supply is unlicensed and its identity and purity cannot be verified.

It is a potent prescription medicine in its approved market, used under medical supervision with dose titration — not a casual research peptide.

UK legal status: not a controlled drug, so possession is not illegal — but "legal to possess" is not the same as safe, approved, or recommended.

Cardiovascular outcome and long-term safety data are still accumulating; the full risk/benefit picture outside the trial setting is not yet established.