Mazdutide

Also known as: IBI362, LY3305677, Xinermei

Evidence: Clinical

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Overview

Oxyntomodulin-based GLP-1 and glucagon receptor dual agonist peptide; approved in China by the NMPA in 2025 for weight management and type 2 diabetes; 14.0% weight loss at 6 mg over 48 weeks in phase 3.

Mazdutide (IBI362, LY3305677) is a 33-residue synthetic analog of mammalian oxyntomodulin carrying a C20 fatty diacid for once-weekly subcutaneous dosing, developed by Eli Lilly with Innovent Biologics. It activates GLP-1 and glucagon receptors and does not target GIP receptors; the triple agonist in the catalog is retatrutide. In phase 3 GLORY-1 (n=610, China), weight fell 11.0% at 4 mg and 14.0% at 6 mg over 48 weeks vs a 0.3% gain on placebo (Ji 2025); 9 mg gave 16.7% at 60 weeks in GLORY-2 (Gao 2026). A US phase 2 by Lilly tested up to 16 mg (Hsia 2026). China's NMPA approved it as Xinermei in June 2025 for long-term weight management and in September 2025 for type 2 diabetes (Shirley 2025). No approval is listed in Drugs@FDA.

Benefits

Weight loss (human phase 3 RCTs), lower HbA1c in type 2 diabetes (human phase 3 RCT), improved cardiometabolic measures (human phase 3 RCT)

Dosing reference

Research dose: 3 to 9 mg once weekly: phase 3 maintenance doses 4, 6 and 9 mg (GLORY-1, GLORY-2, DREAMS-1); phase 2 tested 3 to 6 mg in China and 3 to 16 mg in the US
Range: 3000 to 9000 mcg, 1x weekly
Reconstitution: 2 mL bacteriostatic water
Common vial sizes: 6 mg, 12 mg

Subcutaneous, once weekly. Phase 1b escalated in 4-week steps (2, 4, then 6 mg) over 12 weeks (Ji 2021). GLORY-1 treated for 48 weeks at 4 or 6 mg; GLORY-2 for 60 weeks at 9 mg. The US phase 2 held 3 mg to week 32 before stepping to 6 mg, and also tested 10 and 16 mg (Hsia 2026).

Mechanism

Mazdutide is a long-acting oxyntomodulin analog that binds and activates both the GLP-1 receptor and the glucagon receptor; it has no GIP receptor activity. Preclinical work summarised by Ji 2021 found it lowered body weight in both glucagon-receptor and GLP-1-receptor knockout mice, so each receptor contributes. A C20 diacid joined through gamma-Glu and two OEG spacers to Lys20 binds albumin and gives a terminal half-life of about 6 to 17 days (Ji 2021; PubChem). GLP-1 receptor activity is linked to reduced appetite and glucose-dependent insulin secretion; glucagon receptor activity is proposed to add hepatic fat oxidation and energy expenditure. Heart rate rose with dose, most at 6 mg, in phase 1b (Ji 2021).

Evidence

Clinical: at least one published human trial or an approved drug

Phase 1b, 12 weeks (n=36, China): weight change -4.8% to -6.4% vs +0.6% with placebo; half-life 151 to 404 h (Ji et al., 2021)
Phase 2, 24 weeks (n=248, China): -6.7% (3 mg), -10.4% (4.5 mg), -11.3% (6 mg) vs +1.0% with placebo (Ji et al., 2023)
Phase 3 GLORY-1, 48 weeks (n=610, China): -11.0% (4 mg) and -14.0% (6 mg) vs +0.3% with placebo; adverse-event discontinuation 0.5 to 1.5% (Ji et al., 2025)
Phase 3 GLORY-2, 9 mg, 60 weeks (n=461, BMI 30 or higher): -16.7% vs -1.5% with placebo; vomiting 53.1%, nausea 46.9% (Gao et al., 2026)
Phase 3 DREAMS-1, type 2 diabetes, 24 weeks (n=320): HbA1c -1.57 (4 mg) and -2.15 points (6 mg) vs -0.14 with placebo (Zhu et al., 2026)
Human-trial status: approved in China (NMPA) June 2025 for weight management and September 2025 for type 2 diabetes (Shirley, 2025); no FDA approval; US phase 2 up to 16 mg completed (Hsia et al., 2026)

References

Side effects

Gastrointestinal events dominate. At 9 mg in GLORY-2, vomiting 53.1%, nausea 46.9% and diarrhoea 39.4% vs 1.3%, 3.2% and 6.5% on placebo, mostly mild to moderate; 2.9% stopped (Gao 2026). At 4 to 6 mg, diarrhoea, nausea and decreased appetite were most common (Zhu 2026; Ji 2023). In phase 1b, heart rate rose most at 6 mg and three participants had mild asymptomatic ECG findings (Ji 2021). In the US phase 2, 20% stopped for adverse events at 16 mg (Hsia 2026). GLP-1 class warnings (pancreatitis, gallbladder disease, rodent thyroid C-cell tumours) appear on approved GLP-1 agonist labels; long-term mazdutide data are limited.

Storage

Storage: Refrigerated (2-8°C); general lyophilised-peptide guidance, no compound-specific CoA located
Lyophilized: 24+ months refrigerated
Reconstituted: 28 days refrigerated (general lyophilised-peptide guidance)

Pharmacology

Half-life: 151 to 404 h, individual range (adults with overweight or obesity, subcutaneous); median tmax 72 h (Ji 2021)
Bioavailability: No absolute bioavailability published; slow subcutaneous absorption, Cmax at 12 to 120 h (human, Ji 2021)
Molecular weight: 4476.1 Da
Sequence: H[Aib]QGTFTSDYSKYLDEKKAK[C20 diacid-gamma-Glu-OEG-OEG on Lys20]EFVEWLLEGGPSG-NH2