Mazdutide (IBI362 / LY3305677)
Mazdutide (IBI362) — the first approved GLP-1/glucagon dual agonist: ~20% weight loss, the evidence

Class: peptide
Synonyms: Mazdutide
development codes IBI362 and LY3305677
a GLP-1 / glucagon (GCGR) dual receptor agonist
an oxyntomodulin (OXM) analog. Marketed in China (Innovent). INCI: none
Function tags: metabolic
weight loss
glycaemic (T2D)
(glucagon-driven:) energy expenditure
hepatic fat
visceral-fat reduction
Overall evidence grade: A
WADA prohibited: no
Last updated: 2026-07-13

In brief: Mazdutide is a GLP-1 / glucagon dual-agonist peptide — the same mechanism as Survodutide (#6) — but designed as an oxyntomodulin analog and co-developed by Innovent and Eli Lilly. Its defining fact: in June 2025 it became the first GLP-1/glucagon dual agonist approved anywhere in the world (China NMPA, for weight management; T2D followed in September). The glucagon arm gives it the class-typical extras — increased energy expenditure and hepatic fat oxidation, plus notable visceral-fat reduction — on top of GLP-1 appetite suppression. Efficacy is strong: GLORY-2 reached ~20.1% weight loss at over 60 weeks (the tirzepatide tier) with only a two-step dose titration, and in the DREAMS-3 head-to-head it beat semaglutide on both weight and HbA1c. Tolerability is the usual GLP-1 GI profile (nausea/diarrhea/vomiting, mostly mild-moderate and transient; ~2.9% discontinuation in GLORY-2). The honest caveat: the pivotal evidence is entirely in Chinese populations, and it is approved only in China — global trials/approvals are still pending.

## Identity a **peptide** engineered for **weekly subcutaneous** dosing, **structurally modeled on mammalian oxyntomodulin** — a naturally occurring proglucagon-derived hormone that *already* activates **both** the GLP-1 and glucagon receptors. Co-developed by **Innovent Biologics** and **Eli Lilly** (Lilly China license). Same two-receptor target as Survodutide (#6) — **GLP-1 + glucagon, not GIP** — but reached via the OXM template. ## Mechanism (as proposed) as an **oxyntomodulin analog**, mazdutide co-activates **GLP-1** (appetite suppression, slowed gastric emptying, insulin secretion, glucose lowering) **and glucagon (GCGR)** (**increased energy expenditure** / thermogenesis + **hepatic fat oxidation** + visceral-fat mobilisation). The GLP-1 component offsets glucagon's intrinsic glucose-raising tendency — the same balancing act as Survodutide, and the same reason OXM works naturally without worsening glycaemia. The net effect is potent weight loss *plus* comprehensive metabolic improvement (glucose, lipids, blood pressure, waist).

Evidence grades by outcome:
outcome: Weight loss (obesity, no diabetes)
grade: A
base: Phase 3 GLORY-2 (2025): ~20.1% at / 60 wk; GLORY-1 (NEJM 2025) positive → China NMPA approval
caveat: Approved, strong efficacy — but pivotal data are Chinese-population only; not approved/validated elsewhere yet. The "A" is region-qualified
outcome: Glycemic control (T2D)
grade: A
base: DREAMS-1/-2 (Nature, 2025) vs placebo; DREAMS-3 head-to-head superior to semaglutide → NMPA T2D approval
caveat: Approved for T2D in China; head-to-head win is notable; same population caveat
outcome: Visceral / hepatic fat
grade: B
base: Glucagon-arm effect; reported waist-circumference, lipid, BP improvements
caveat: Consistent metabolic benefits reported; dedicated MASH-histology program less developed than Survodutide's
outcome: Cardiometabolic risk factors (BP, lipids, waist)
grade: B
base: Phase 3 secondary endpoints
caveat: Improvements reported alongside weight/glucose; long-term CV-outcome trial not the headline here
outcome: Safety / tolerability
base: Phase 1b→3 (GLORY/DREAMS)
caveat: GI predominant (nausea ~21–41%, diarrhea, vomiting — dose-escalation, then settle); mild-moderate; only 2.9% discontinued in GLORY-2; glucagon arm still requires glucose-balanced titration (like all GCGR/GLP-1 duals)

Legal status:
region: EU
status: Not approved
note: not approved outside China; investigational elsewhere. Not a cosmetic; no compounding pathway.

Cosmetic claims:

Note: Survodutide's twin — same mechanism, but this one is already approved. Three points make this entry land: (1) it's the same GLP-1 / glucagon dual class as Survodutide (#6), but built as an oxyntomodulin analog — and, crucially, it is the first GLP-1/glucagon dual agonist approved anywhere in the world (China NMPA, 2025); (2) its Phase 3 GLORY-2 hit ~20.1% weight loss — matching the tirzepatide tier — with just a two-step titration; (3) in a head-to-head trial it beat semaglutide (DREAMS-3). This is the entry that shows "investigational vs approved" within the same mechanism.
Status note: China-approved; watch for global (non-Chinese) trials and any ex-China regulatory filing, which would change the region-qualified grades

Sources:
Innovent Biologics — NMPA approvals: weight management (June 2025), T2D (Sept 2025); GLORY-2 topline (Nov 2025, ~20.1%).
GLORY-1 — Phase 3 obesity, NEJM (May 2025).
DREAMS-1 & DREAMS-2 — Phase 3 T2D, published back-to-back in Nature (2025); DREAMS-3 head-to-head vs semaglutide (superiority; DDW/Innovent 2025).
Ji L, et al. IBI362 (LY3305677) weekly GLP-1/glucagon dual agonist, Phase 1b. EClinicalMedicine 2021; and / multiple-ascending-dose Phase 1b, EClinicalMedicine 2022.
Deng CX, et al. Mazdutide: an emerging GCGR/GLP-1 dual agonist for obesity. World J Pharmacol. 2026; oxyntomodulin dual-agonist rationale (Wharton, Diab Obes Metab 2026).