# Mazdutide: Evidence, Mechanism, Dosing & Legal Status

> A clinical monograph on mazdutide (IBI362 / LY3305677) — the first GLP-1/glucagon dual receptor agonist, backed by completed Phase 3 RCTs for obesity and type 2 diabetes, approved in China but investigational in the US.

*Published 2026-06-30 · Updated 2026-07-01 · By Marcus Feld, PharmD, BCPS*

The short answer
Mazdutide (IBI362 / LY3305677) is a **genuinely de-risked, RCT-proven GLP-1/glucagon dual receptor agonist** — not a speculative peptide. Its highest evidence grade is **A**, resting on multiple completed Phase 3 trials for both weight loss and type 2 diabetes. It is **approved in China** (obesity June 2025, T2D September 2025) but **not FDA-approved** in the US, where it remains investigational under Eli Lilly.[1](https://peptidevox.com/#r1)[11](https://peptidevox.com/#r11)

Mazdutide is a synthetic, acylated analog of oxyntomodulin (OXM) — a natural gut hormone — engineered for once-weekly subcutaneous dosing as a treatment for obesity and type 2 diabetes.[14](https://peptidevox.com/#r14) It carries the developer codes IBI362 (Innovent Biologics) and LY3305677 (Eli Lilly), reflecting its co-development.[15](https://peptidevox.com/#r15) Unlike most peptides covered in this encyclopedia, its evidence base is mature human trial data, not preclinical extrapolation. This monograph separates what is proven from what remains uncertain.

*This article is informational and editorial content for research and educational purposes only. It is not medical advice, not a protocol to follow, and not a sourcing guide. Mazdutide is a prescription drug — approved in China and investigational in the US — and is not FDA-approved. Dosing figures are reported strictly as seen in the published literature and clinical trials for completeness, not as recommendations. Consult a licensed clinician before any health decision.*

## What is mazdutide and how does it work?

Mazdutide is an analog of oxyntomodulin, a naturally occurring gut hormone that intrinsically activates both the GLP-1 and glucagon receptors.[14](https://peptidevox.com/#r14) To convert the short-lived native peptide into a once-weekly drug, several engineering modifications were made: the position-2 serine was substituted with aminoisobutyric acid (Aib) to resist DPP-4 cleavage; methionine-27 was substituted with leucine to remove an oxidation liability; the helical topology was stabilized with a bifurcated salt bridge; and a fatty-acyl moiety was added to drive albumin binding and extend half-life.[15](https://peptidevox.com/#r15)[16](https://peptidevox.com/#r16)

The defining feature is dual receptor engagement. Unlike single-target GLP-1 agonists (semaglutide, liraglutide) or the GLP-1/GIP co-agonist tirzepatide, mazdutide activates both the GLP-1 receptor (GLP-1R) and the glucagon receptor (GCGR), with reported in-vitro binding affinities of approximately Ki 17.7 nM at GLP-1R and 28.6 nM at GCGR.[15](https://peptidevox.com/#r15) The GLP-1 arm suppresses appetite, augments glucose-dependent insulin secretion, and slows gastric emptying; the glucagon arm adds thermogenesis, hepatic fatty-acid oxidation, and direct lipolysis — which the developers credit for the unusually large hepatic-fat reductions seen in trials.[11](https://peptidevox.com/#r11)[1](https://peptidevox.com/#r1) From a functional, root-cause lens, this is mechanistically attractive because it targets both energy intake and energy expenditure plus hepatic lipid handling, rather than appetite alone — though the glucagon component is also why this class is monitored differently from pure GLP-1 drugs. In Phase 1b pharmacokinetics, single-dose exposure at 2.5–3 mg showed a median Tmax around 72 hours and a wide terminal half-life of roughly 7.3 to 44.8 days, long enough to support once-weekly administration.[2](https://peptidevox.com/#r2)

## What is the evidence by indication?

Mazdutide's two best-evidenced uses — chronic weight management and glycemic control in type 2 diabetes — both rest on completed Phase 3 randomized controlled trials, grading to evidence level A.[1](https://peptidevox.com/#r1)[7](https://peptidevox.com/#r7) The trial program is largely China-based, organized as the GLORY obesity series and the DREAMS diabetes series.

  Mazdutide evidence by indication

    IndicationBest evidenceGrade

    Obesity / chronic weight managementGLORY-1 (Phase 3, n=610) and GLORY-2 (Phase 3, 9 mg) randomized, placebo-controlled trialsA (human Phase 3 RCTs)
    Type 2 diabetes / glycemic controlDREAMS-1, DREAMS-2 (vs dulaglutide), and DREAMS-3 (vs semaglutide) Phase 3 trialsA (human Phase 3 RCTs)
    MASLD/MASH, OSA, HFpEF, adolescentsActive Phase 3 / ongoing trials (GLORY-3, GLORY-OSA, others), no published efficacy yetB / ongoing

The obesity evidence is the headline. GLORY-1 — a randomized, double-blind, placebo-controlled Phase 3 trial of 610 Chinese adults registered as [NCT05607680](https://clinicaltrials.gov/study/NCT05607680) — randomized participants to mazdutide 4 mg, 6 mg, or placebo, given subcutaneously once weekly for 48 weeks.[1](https://peptidevox.com/#r1) Mean body-weight change at week 48 was −12.05% (4 mg) and −14.84% (6 mg) versus −0.47% for placebo; ≥10% loss was reached by 55.2% and 67.9% of treated participants versus 2.9% on placebo.[1](https://peptidevox.com/#r1)[5](https://peptidevox.com/#r5) Hepatic fat content fell dramatically — in those with baseline ≥10%, by −65.85% (4 mg) and −80.24% (6 mg) versus −5.27% for placebo — alongside reductions in blood pressure, lipids, and uric acid.[1](https://peptidevox.com/#r1) GLORY-2 then tested 9 mg and reported a mean 20.08% weight reduction at week 60 in the non-diabetic subgroup, with 48.7% achieving ≥20% loss and weight loss continuing through 60 weeks without plateau.[6](https://peptidevox.com/#r6) Earlier Phase 1b and Phase 2 work established the dose-ranging that informed these doses.[2](https://peptidevox.com/#r2)[3](https://peptidevox.com/#r3)

For type 2 diabetes, the DREAMS series is equally mature. DREAMS-1 reported HbA1c reductions of −1.58% (4 mg) and −2.02% (6 mg) versus −0.25% for placebo at week 24, and DREAMS-2 showed comparable or better control versus dulaglutide 1.5 mg.[7](https://peptidevox.com/#r7) Most striking is DREAMS-3, a head-to-head Phase 3 against semaglutide 1 mg in 349 adults with T2D plus obesity over 32 weeks: mazdutide 6 mg achieved an HbA1c reduction of −2.03% versus −1.84% and weight loss of 10.29% versus 6.00%, and the composite primary (HbA1c Proven vs uncertain
Proven: robust, RCT-grade weight loss and HbA1c reduction in Chinese adults, with a head-to-head edge over semaglutide on a combined glycemic-plus-weight endpoint. Uncertain or unproven: generalizability to non-Asian and older populations (GLORY cohorts were young, mean age ~34, with lower baseline BMI), long-term cardiovascular outcomes, durability against immunogenicity, and the full implications of chronic glucagon-receptor agonism. Extended indications (MASH, OSA, HFpEF, adolescents) are in active trials but lack published efficacy.[1](https://peptidevox.com/#r1)[13](https://peptidevox.com/#r13)

## What doses appear in the literature?

Reported strictly as information, not a protocol. Mazdutide is given by subcutaneous injection once weekly, a schedule supported by its 7.3-to-44.8-day terminal half-life.[1](https://peptidevox.com/#r1)[2](https://peptidevox.com/#r2) Maintenance doses studied were 4 mg, 6 mg, and 9 mg weekly: GLORY-1 used 4 mg and 6 mg over 48 weeks, GLORY-2 used 9 mg over 60 weeks, and ascending-dose work explored up to 10 mg.[1](https://peptidevox.com/#r1)[6](https://peptidevox.com/#r6) Trials used gradual dose escalation — for example 3 to 6 to 9 mg, or 2.5 to 5 to 7.5 to 10 mg, in roughly four-week steps — to mitigate gastrointestinal adverse events, the standard incretin-class ramp.[2](https://peptidevox.com/#r2) The approved Chinese indications cover chronic weight management in adults with BMI ≥28 (or ≥24 with at least one weight-related comorbidity) and glycemic control in adults with T2D.[10](https://peptidevox.com/#r10) These figures describe the manufactured, clinically supervised drug as studied; lyophilized 'research-chemical' vendor vials are unapproved and are not a legitimate clinical product, so no reconstitution protocol is endorsed here.

## How safe is mazdutide?

The most common adverse events are dose-dependent and mostly mild to moderate, concentrated during titration: nausea, vomiting, diarrhea, decreased appetite, and abdominal distension — the typical GLP-1-class gastrointestinal profile.[2](https://peptidevox.com/#r2) In the small Phase 1b study, decreased appetite and nausea each affected up to about 62.5% of the 9 mg cohort, but all treatment-emergent events were mild or moderate with no serious adverse events and no AE-related discontinuations; Phase 3 (GLORY-1) confirmed the same class profile with low discontinuation and no signal of increased cardiovascular risk.[2](https://peptidevox.com/#r2)[1](https://peptidevox.com/#r1) Signals to watch include a heart-rate increase (up to ~+17 bpm acutely at 9 mg in Phase 1b, around +2.6 bpm at steady doses in GLORY-1), transient lipase elevation without pancreatitis, and immunogenicity, with anti-drug antibodies appearing in a minority of early participants including one neutralizing antibody to the glucagon-receptor activity.[2](https://peptidevox.com/#r2)

Because glucagon agonism can raise hepatic glucose output and influence lipid metabolism, the dual mechanism warrants attention to glycemia and hepatic function — even though trials showed net glucose lowering and hepatic-fat reduction, this is why the class is monitored differently from pure GLP-1 drugs.[11](https://peptidevox.com/#r11) Class-level cautions, extrapolated from the GLP-1 class, include personal or family history of medullary thyroid carcinoma or MEN2, history of pancreatitis, gallbladder disease, severe gastrointestinal disease, and hypersensitivity. Delayed gastric emptying can alter absorption of oral co-medications, and combination with insulin or sulfonylureas raises hypoglycemia risk.[2](https://peptidevox.com/#r2) There are no human safety data in pregnancy or lactation, so it should be treated as contraindicated absent specific clinical guidance.

## What is the regulatory and anti-doping status in 2026?

In China, mazdutide is approved by the NMPA for chronic weight management (announced June 27, 2025) and for glycemic control in adults with type 2 diabetes (September 2025) — the world's first GCG/GLP-1 dual receptor agonist approved in either indication, with a 9 mg supplementary application for moderate-to-severe obesity under review.[11](https://peptidevox.com/#r11)[10](https://peptidevox.com/#r10)[12](https://peptidevox.com/#r12) In the United States it is not approved — it is investigational, with Eli Lilly holding US rights and running an obesity Phase 2; commentators project a possible FDA approval only after Phase 3, around 2028–2029, and there is no FDA label or DailyMed entry.[11](https://peptidevox.com/#r11) Mazdutide sold as a research-only peptide labeled 'not for human use' is not FDA-approved, and using such material for human consumption falls outside lawful therapeutic use.[18](https://peptidevox.com/#r18)

For athletes, mazdutide is not individually listed on the WADA Prohibited List as of this writing, and metabolic or anti-obesity agents are not an established prohibited category. However, as a non-approved/investigational substance, off-label or non-approved use can implicate WADA category S0 (Non-Approved Substances); athletes should confirm current status and seek a Therapeutic Use Exemption where relevant.[19](https://peptidevox.com/#r19)

**Bottom line.** Mazdutide is one of the most de-risked compounds in this encyclopedia: Grade A human evidence supports both weight loss (~11–15% at 4–6 mg, up to ~20% at 9 mg) and glycemic control in T2D (HbA1c −1.6 to −2.0%), with a head-to-head Phase 3 edge over semaglutide and striking hepatic-fat reduction that plausibly reflects the glucagon arm. What remains uncertain is generalizability beyond the young, lower-BMI Chinese cohorts, long-term cardiovascular outcomes, and the implications of chronic glucagon agonism. Crucially, the legitimate evidence is for the manufactured, clinically supervised drug — not 'research-chemical' vials. Regulatory facts here are current as of June 2026 and should be re-verified, particularly any US FDA developments.

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Source: https://peptidevox.com/peptide-encyclopedia/mazdutide
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