Evidence Grade C — Moderate human evidence. 39 published studies, 28 human. 31 registered clinical trials.
Medically reviewed by a licensed medical professional
Mazdutide is a dual GLP-1/glucagon receptor agonist developed primarily in China, where it has already been approved for weight management — making it the first drug in its class to reach any market. The glucagon component adds a mechanism that increases energy expenditure and burns liver fat, complementing the appetite suppression from GLP-1. Development for markets outside China is ongoing.
Mazdutide is also known by these brand and alternate names:
39 published studies: 28 human, 1 animal, 1 in-vitro, 22 reviews
Mazdutide has been approved in China (as Moshutai) for weight management and is in Phase III development for other markets. In the Chinese Phase III GLORY-1 trial (610 patients), the 6 mg dose achieved approximately 15% weight loss at 48 weeks with 80% liver fat reduction in participants with baseline hepatic steatosis.
Mazdutide's approval in China makes it the first dual GLP-1/glucagon agonist to receive marketing authorisation anywhere. The dramatic liver fat reduction may position it strongly for metabolic liver disease indications. Development for non-Chinese markets is ongoing.
Mazdutide combines GLP-1 receptor activation (appetite suppression) with glucagon receptor activation (increased energy expenditure and liver fat burning), similar in concept to survodutide (#160). The glucagon component directly stimulates hepatic fat oxidation, which produces significant liver fat reduction alongside weight loss.
In the Chinese Phase III GLORY-1 trial (610 patients), the highest dose achieved approximately 15% weight loss at 48 weeks, with an 80% reduction in liver fat in participants who had fatty liver at baseline. The dramatic liver fat reduction may position mazdutide strongly for metabolic liver disease, a massive unmet need. Head-to-head data showed superiority over semaglutide for both weight loss and blood sugar control in Chinese patients. Key limitations include that all Phase III evidence comes from Chinese populations only, and development outside China remains at Phase II. Eli Lilly holds the rights for markets outside China, and their Phase 2 trial results will determine whether a global filing is pursued. Remarkably low discontinuation rates (0.5-2.9%) suggest favourable tolerability. Survodutide, a competing dual GLP-1/glucagon agonist from Boehringer Ingelheim, is also in advanced development.
PeptideTrace tracks 31 registered clinical trials for Mazdutide sourced from ClinicalTrials.gov.
Efficacy and Safety of IBI362 in Hypertensive Patients With Overweight/Obesity
ASCEND-1: Lifestyle Intervention Plus Mazdutide for Weight Management
A Study of HDM1005 in Participants With T2DM Not Controlled With Metformin Alone or in Combination With a Sodium-Glucose Cotransporter 2 (SGLT2) Inhibitor
A Study of IBI362 in Chinese Adolescents With Obesity or Overweight
Mazdutide as Adjuvant Therapy Following Sleeve Gastrectomy in Severe Obesity
Mazdutide (IBI362/LY3305677) is a 34-amino-acid oxyntomodulin analog with C20 fatty diacid acylation, developed by Innovent Biologics (China rights) and Eli Lilly (ex-China rights). Molecular weight approximately 4,476-4,563 Da; molecular formula C207H317N45O65. CAS number: 2259884-03-0. Trade name: Xinermei (China). The compound received NMPA approval in China for obesity in June 2025 and for type 2 diabetes in September 2025, making it the world's first approved dual GCG/GLP-1 receptor agonist. Eli Lilly is conducting a separate US Phase 2 trial with approximately 179 participants.
Mazdutide provides dual agonism at GLP-1R (Ki 28.6 nM) and GCGR (Ki 17.7 nM). The GLP-1 component suppresses appetite, delays gastric emptying, and enhances insulin secretion. The glucagon receptor component directly stimulates hepatic lipid oxidation, promotes thermogenesis, and induces FGF21 secretion, while GLP-1 activity offsets glucagon's potential hyperglycemic effects. This dual mechanism provides both weight loss and direct hepatic metabolic benefits.
GLORY-1 Phase 3 (NCT05607680; N=610; NEJM May 2025): the 6 mg dose achieved -14.84% weight loss at 48 weeks (efficacy estimand) versus -0.47% placebo, with liver fat reduction of -80.2% in participants with baseline hepatic steatosis of at least 10%. GLORY-2 (N approximately 450): the 9 mg dose achieved -18.55% at 60 weeks with 44.0% of participants achieving at least 20% weight loss. DREAMS-1 (N approximately 320): HbA1c reduction of -2.15% at 6 mg. DREAMS-3 head-to-head versus semaglutide: mazdutide demonstrated superior weight loss (-10.29% versus -6.00%; P<0.05) and composite endpoint (48.0% versus 21.0%; P<0.0001). Treatment discontinuation rates were remarkably low at 0.5-2.9% across Phase 3 trials, and two Phase 3 results were published back-to-back in Nature in 2025.
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Semaglutide is one of the most extensively studied peptide medications available today, with clinical trial data spanning over 50,000 patients. It is sold as Ozempic for type 2 diabetes (approved 2017), Rybelsus as an oral tablet for diabetes (approved 2019), and Wegovy for weight management (approved 2021). Wegovy has since received additional approvals for reducing heart attack and stroke risk, for use in adolescents aged 12 and older, and for liver disease related to obesity. In clinical trials, patients taking Wegovy lost an average of 14.9% of their body weight over 68 weeks, and the SELECT trial demonstrated a 20% reduction in major cardiovascular events such as heart attack and stroke. Research is now exploring its potential in early Alzheimer's disease. The main side effects are gastrointestinal, particularly nausea, and a key limitation is that most weight tends to return after stopping treatment.
Bimagrumab is in Phase II/III development (not yet approved). A Phase II trial (75 patients with type 2 diabetes and obesity) showed 20.5% fat mass reduction with 3.6% lean mass increase — essentially reshaping body composition without net appetite suppression. The BELIEVE Phase IIb trial (507 patients) showed that bimagrumab plus semaglutide achieved 22% weight loss with the weight lost being 88% fat — significantly better body composition than semaglutide alone. Bimagrumab is not a peptide. Its strategic significance is as a combination partner to address the muscle loss problem inherent in weight loss with current obesity drugs. Eli Lilly's acquisition positions it alongside tirzepatide.
Pemvidutide is in Phase II/III development (not yet approved). In the MOMENTUM Phase II trial (391 patients, 48 weeks), the 2.4 mg dose achieved 15.6% weight loss. Body composition analysis showed 78% of weight lost was fat mass, with only 22% lean mass — a favourable ratio. A Phase IIb MASH trial (212 patients) showed MASH resolution in up to 75% of patients at the highest dose. Pemvidutide's balanced receptor profile and no-titration dosing regimen represent potential practical advantages. The high rate of MASH resolution in Phase II positions it as a candidate for liver disease indications alongside obesity.
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