Mazdutide

What Is Mazdutide?

Mazdutide is a synthetic peptide that activates both the glucagon receptor and the GLP-1 receptor. It is being developed by Eli Lilly and Company together with Innovent Biologics for weight management in adults with obesity or overweight and for type 2 diabetes.^[1]

The compound appears in the literature under two development codes, LY3305677 and IBI362.^[2] It belongs to the group of glucagon co-agonists, alongside survodutide, that combine GLP-1 receptor activity with glucagon receptor activity.^[3] This sets it apart from selective GLP-1 receptor agonists such as semaglutide and from the GIP/GLP-1 dual agonist tirzepatide.

Most of mazdutide’s clinical data come from trials in Chinese adults, and its first regulatory approvals were in China.^[1][4]

Chemical Structure and Molecular Identity

Mazdutide is a 33-residue linear peptide with one non-coded amino acid and a fatty-acid side chain. PubChem (CID 167312357) lists the molecular formula as C207H317N45O65 and the molecular weight as 4476 g/mol; the CAS Registry Number is 2259884-03-0.

Structural features

• N-terminus: a free histidine followed by alpha-aminoisobutyric acid (Aib) at position 2.
• Lipidation: the lysine 20 side chain carries an eicosanedioic acid (C20 diacid) attached through a gamma-glutamic acid spacer and two 8-amino-3,6-dioxaoctanoic acid linkers.
• C-terminus: a glycine amide.

The fatty diacid and linker are the same type used in tirzepatide, although the two peptide backbones differ. PubChem lists IBI-362 and IBI362 among the compound’s synonyms. Because of the Aib residue and the lipidated lysine, the sequence cannot be written entirely in standard one-letter amino-acid code.

Research History and Development

Mazdutide went through phase 1 and phase 2 trials in China between 2021 and 2023. Phase 3 trials in obesity and type 2 diabetes followed, leading to approvals in China in 2025.^[5][6][1]

Phase 1 and phase 2

A phase 1b trial at nine centers enrolled 43 Chinese patients with type 2 diabetes in three cohorts and compared mazdutide with placebo and open-label dulaglutide over 12 weeks.^[5] Earlier phase 1 work in adults with overweight or obesity reported 12-week weight loss of up to 6.4%. A follow-up phase 1b trial at five hospitals then tested higher dose cohorts in 24 participants, with safety and tolerability as primary outcomes.^[2] A phase 2 trial at 20 Chinese hospitals randomized 248 adults with overweight or obesity to three dose levels or placebo for 24 weeks.^[6]

Phase 3 and approval

A 48-week phase 3 trial in 610 Chinese adults with obesity, or overweight plus a weight-related condition, compared two dose levels with placebo. Participants had a mean baseline body weight of 87.2 kg and a mean BMI of 31.1.^[4] Two phase 3 trials in type 2 diabetes compared mazdutide with placebo in 320 participants and with dulaglutide in 731 participants. The placebo-controlled trial enrolled adults with a mean HbA1c of 8.24% and a diabetes duration of 1.9 years, and its 24-week double-blind period was followed by a 24-week extension.^[7][8] In June 2025, mazdutide received its first approval, in China, for long-term weight management in adults with obesity or overweight. A second Chinese approval followed in September 2025 for glycemic control in adults with type 2 diabetes.^[1]

Mechanisms Studied in Research

Mazdutide is designed to combine GLP-1 receptor signaling, which lowers glucose and appetite, with glucagon receptor signaling. Reviewers describe next-generation multi-receptor agonists as acting on energy uptake, storage and expenditure through synergistic mechanisms.^[1][3]

Pharmacodynamic signals in humans

In the phase 1b trial in type 2 diabetes, HbA1c, fasting plasma glucose and post-meal glucose after a mixed-meal tolerance test all fell from baseline in each mazdutide cohort.^[5] Decreased appetite was among the most frequent adverse events in that trial and in a phase 3 trial against placebo, which is consistent with GLP-1 receptor activity.^[5][7]

Evidence gaps

The peer-reviewed abstracts reviewed for this page are clinical trials, reviews and a regulatory profile. They do not include dedicated cell-based or animal mechanistic studies, so the separate contributions of glucagon and GLP-1 receptor activity to mazdutide’s effects are not described here.

Key Findings From Published Studies

Phase 2 and phase 3 trials in Chinese adults report that mazdutide reduces body weight and HbA1c compared with placebo, and that it outperformed dulaglutide on both measures. Gastrointestinal events were the most common adverse effects.^[6][4][7][8]

Obesity

In the phase 3 obesity trial, body weight at week 32 had fallen by 10.09% and 12.55% in the two mazdutide arms, compared with a 0.45% gain on placebo. A weight reduction of at least 5% was reached by 73.9% and 82.0% of participants, versus 10.5% on placebo.^[4] In phase 2, treatment differences versus placebo ranged from −7.7% to −12.3%.^[6] A 2025 systematic review reported that completed phase 2 trials of incretin-based therapies showed mean weight loss of 7.4% to 24.2%.^[9]

Type 2 diabetes

In the placebo-controlled diabetes trial, body weight fell by 5.61% and 7.81% at week 24 versus 1.26% on placebo, and more participants reached HbA1c below 7.0%.^[7] Against dulaglutide, mazdutide produced greater weight loss, with treatment differences of −3.78% and −5.76%.^[8]

Safety signals

Diarrhea, nausea and vomiting or decreased appetite were the most common adverse events across trials. Gastrointestinal events were more frequent with mazdutide than with dulaglutide.^[6][7][8] In the phase 1b diabetes trial, diarrhea occurred in 29.2% of mazdutide recipients, 33.3% of dulaglutide recipients and none on placebo.^[5]

For a 33-residue lipidated peptide like mazdutide, batch-specific HPLC and mass-spectrometry certificates of analysis are the practical way to confirm identity and purity.

Regulatory and Research Status

Mazdutide is approved in China, under its generic name, for long-term weight management and for glycemic control in type 2 diabetes. It is not FDA approved.^[1] It is one of five GLP-1 receptor agonist-based drugs approved for weight management in China since 2021.^[10]

Mazdutide is under clinical evaluation in metabolic dysfunction-associated fatty liver disease, obstructive sleep apnea and alcohol use disorder.^[1] A 2025 systematic review listed it among the GLP-1/glucagon receptor agonists in ongoing phase 3 obesity trials. The same review identified a need for data on mortality, cardio-renal-metabolic events and long-term weight maintenance across emerging obesity drugs.^[9]

Outside its approved uses in China and registered clinical trials, material described as mazdutide is intended for laboratory research only. This page summarizes published findings and does not provide guidance on human use.