Mazdutide.
Mazdutide (IBI362, originally LY3305677) is an investigational once-weekly injectable dual agonist of the GLP-1 and glucagon receptors, based on a mammalian oxyntomodulin analog.
Mazdutide (IBI362, originally LY3305677) is an investigational once-weekly injectable dual agonist of the GLP-1 and glucagon receptors, based on a mammalian oxyntomodulin analog. Mazdutide is in human trials, and PepCue grades its published evidence B tier (68/100). Also known as IBI362 · LY3305677. This is a research reference, not medical or dosing advice.
What it is
Mazdutide (IBI362, originally LY3305677) is an investigational once-weekly injectable dual agonist of the GLP-1 and glucagon receptors, based on a mammalian oxyntomodulin analog. It is being developed by Innovent Biologics under a license from Eli Lilly, primarily for obesity and type 2 diabetes and with additional metabolic indications under study. It is furthest advanced in China, where it has progressed through Phase 3 trials, but it is not an approved medicine in the United States or Europe. Like other dual agonists, it is designed to pair appetite and glucose control with added energy expenditure.
How it works
Mazdutide derives from oxyntomodulin, a natural gut hormone that engages both the GLP-1 and glucagon receptors. GLP-1 activation drives appetite suppression, delayed gastric emptying, and glucose-dependent insulin release, while glucagon-receptor activation is thought to increase energy expenditure and reduce hepatic fat. The combined signaling is intended to produce weight loss alongside improvements in lipids, blood pressure, liver enzymes and other metabolic markers. Structural modifications extend its half-life to allow weekly subcutaneous administration.
Mechanism pathways
Activating the GLP-1 receptor to enhance insulin release, slow gastric emptying, and reduce appetite.
Glucagon-like peptide-1 is an incretin hormone released from the gut after a meal. Its receptor is a class B G-protein-coupled receptor found on pancreatic beta cells, on stomach and gut tissue, and on neurons in the hypothalamus and brainstem, including the area postrema. When the receptor is activated, three things happen at once. Beta cells become more responsive to glucose, so insulin secretion rises mainly when blood glucose is already elevated rather than continuously, which is why this class carries a lower intrinsic hypoglycaemia risk than insulin itself. The stomach empties more slowly, flattening the rise in glucose after eating and prolonging the sense of fullness. Central appetite circuits shift toward satiety, reducing the drive to eat between meals. Glucagon secretion is also suppressed when glucose is high. Many compounds target this receptor because native GLP-1 is degraded within minutes by dipeptidyl peptidase-4. Almost every design problem in the class is a half-life problem, and the answers differ. Some analogs attach a fatty-acid chain so the molecule binds albumin and circulates far longer. Others alter the amino acids around the cleavage site so the enzyme cannot act. These structural choices set how often a compound is given and how steeply blood levels rise and fall, which in turn shapes how much nausea a person experiences during the early adjustment period. The class also splits by how many receptors a molecule touches. Pure GLP-1 agonists engage this pathway alone. Dual and triple agonists add GIP, glucagon, or amylin activity on top of it, and combination products pair a GLP-1 agonist with a separate molecule. In every case the GLP-1 arm remains the backbone of the metabolic effect. Of all the pathways described on this site, this one has the strongest and most mature clinical footing. Several GLP-1 receptor agonists are approved medicines for type 2 diabetes, for obesity, or both, and the mechanism has been characterised in humans rather than inferred from animal work. That does not make every molecule in the class equivalent. Some listed here are still investigational, and their receptor activity being well understood says nothing about whether their particular formulation, purity, or long-term profile has been established.
Engaging the glucagon receptor to raise energy expenditure and mobilise liver fat.
Glucagon is the counter-regulatory partner to insulin, released from pancreatic alpha cells when blood glucose falls. Its receptor is a class B G-protein-coupled receptor concentrated in the liver, with additional expression in kidney, heart, and adipose tissue. Classical glucagon signalling raises blood glucose by driving glycogen breakdown and gluconeogenesis in the liver, which on its face makes it a strange thing to activate deliberately in someone with a metabolic disorder. The rationale rests on glucagon's other actions. Glucagon receptor signalling in the liver also promotes fatty-acid oxidation and reduces hepatic fat accumulation, and across the body it is associated with a rise in resting energy expenditure. In other words it increases the rate at which energy is burned rather than only the rate at which food is refused. Combining that with GLP-1 activity is intended to cancel the unwanted half of the effect: the GLP-1 arm suppresses appetite and improves glucose handling strongly enough to offset the glucose-raising tendency of the glucagon arm, leaving the energy expenditure and liver fat benefits behind. Compounds here take different routes to the same idea. Some are rationally designed multi-agonists built to hit a specific ratio across two or three receptors. Others are derived from oxyntomodulin, a naturally occurring gut hormone that already engages both the GLP-1 and glucagon receptors, and are then modified for stability and duration. The balance between the two arms is the central design variable, and it differs meaningfully between agents. A molecule weighted more heavily toward glucagon may do more for liver fat while demanding more careful attention to glucose. This is a less mature pathway than GLP-1 agonism. No glucagon-receptor-containing agent has the depth of approved-medicine history that pure GLP-1 agonists have, and several of the compounds listed here are still in clinical development rather than in general use. The underlying physiology of glucagon is well established, and the metabolic logic of combining it with an incretin is coherent, but the long-term consequences of chronically raising glucagon signalling in people, including effects on glucose control and cardiovascular parameters over years, are still being worked out. It is also worth noting that the amount of glucagon activity a molecule carries is a design choice made in the laboratory, not something a user can adjust, so comparisons between agents in this class are comparisons between fixed ratios rather than between adjustable ones.
The evidence
A randomised, double-blind, placebo-controlled Phase 2 trial in 248 Chinese adults with overweight or obesity, published in Nature Communications (2023), tested mazdutide 3 mg, 4.5 mg and 6 mg over 24 weeks. Mean body-weight reductions reached roughly 11% at the 6 mg dose versus about 3% with placebo, with dose-dependent effects. Participants also showed improvements in waist circumference, blood pressure, blood lipids, liver transaminases and serum uric acid. Earlier Phase 1b studies in Chinese adults with overweight/obesity and with type 2 diabetes supported tolerability and metabolic benefit at higher doses. Phase 3 obesity and diabetes programs (the GLORY series) have since been conducted in China, and GLORY-1, a randomised placebo-controlled Phase 3 trial of once-weekly mazdutide in Chinese adults with obesity or overweight, was published in the New England Journal of Medicine in 2025. A further Phase 2 randomised controlled trial in Chinese adults with a body mass index of at least 30 and without diabetes was reported in Med, and mazdutide has been included in network meta-analyses of glucagon receptor agonists that pool metabolic outcomes across compounds. Evidence outside Chinese populations and long-term outcome data remain limited. The trials are sponsor-run, of moderate size, and almost entirely single-country, so generalisability to other ancestries, body-composition distributions and background diets is untested. There is no cardiovascular outcome trial for mazdutide, no published head-to-head randomised comparison with semaglutide or tirzepatide, and no multi-year durability or weight-regain dataset. By contrast, semaglutide and tirzepatide each have global multi-thousand-participant Phase 3 programs and regulatory approval in the United States and Europe, and semaglutide additionally has dedicated cardiovascular outcome data, which places mazdutide an evidence tier behind them despite broadly similar reported weight reductions. Regulatory acceptance in one country also does not substitute for the outcome evidence that has not yet been generated.
The evidence, in brief
An investigational once-weekly GLP-1/glucagon dual agonist derived from oxyntomodulin, developed by Innovent under licence from Eli Lilly. A randomized placebo-controlled phase-2 trial in 248 Chinese adults reported about 11% mean weight loss at the highest dose over 24 weeks, alongside improvements in waist, blood pressure, lipids and liver enzymes. Development is most advanced in China; it is not FDA or EMA approved, and data outside Chinese populations remain limited.
- Ji L et al.: A phase 2 randomised controlled trial of mazdutide in Chinese adults with overweight or obesityNat Commun, 2023 (PMID 38092790)
- PubMed search: mazdutidePubMed / NCBI
Evidence maturity
An evidence-only reading: approval status, human vs preclinical data, mechanism and safety. Popularity never raises it. Research file #040
Meaningful human evidence; not yet definitive.
Studied in human clinical trials; evidence is meaningful.
Claim receipts
Popular claims about Mazdutide, checked against the state of the evidence. The verdict describes evidence maturity, never an invented study result.
Phase 3 work is most advanced there, but regulatory acceptance in one country does not supply the outcome evidence that has not been generated.
No published head-to-head randomized comparison exists, and the trials are largely single-country.
Trials reported improvements in waist, blood pressure, lipids, liver enzymes and uric acid, which are markers rather than clinical outcomes.
It is not approved or commercially supplied there, so anything sold comes from unregulated channels.
Gastrointestinal effects were the most common adverse events, and uncommon or long-term risks are not established.
Safety profile
Across trials, the most common adverse events were gastrointestinal, including nausea, diarrhoea and decreased appetite, typical of GLP-1-based agents and generally most pronounced during dose escalation. Overall tolerability was described as favorable in the Phase 2 study, but as an investigational drug its full safety profile, including uncommon and long-term risks, is not yet established. Glucagon-receptor activation warrants monitoring of parameters such as heart rate and hepatic markers in ongoing studies. Documented class considerations for incretin-based agents include gallbladder and biliary events, reported pancreatitis, delayed gastric emptying with implications for sedation and anaesthesia, loss of lean mass in parallel with fat loss, and rodent thyroid C-cell findings that shaped labelling for several approved GLP-1 drugs. A trial adequate to characterise these requires scheduled laboratory chemistry, vital-sign monitoring, pregnancy prevention requirements, protocol-defined dose-reduction and stopping rules, and independent adjudication of serious events, none of which exists outside a regulated study. Mazdutide is not approved or commercially supplied in the United States or Europe, so material sold there as mazdutide comes from unregulated research-chemical or compounding channels with no verified identity, potency, purity or sterility, no stability data, and no route for reporting harm. Peptide products from such channels have been associated with mislabelling and contamination, which makes any observed effect, benign or adverse, difficult to attribute to the intended molecule.
Compound notes
- Mazdutide (IBI362, originally LY3305677) is an investigational dual GLP-1 and glucagon receptor agonist based on an analog of oxyntomodulin, a natural gut hormone that engages both receptors.
- It is developed by Innovent Biologics under license from Eli Lilly and is structurally modified for a long half-life permitting weekly subcutaneous injection.
- A Phase 2 trial in 248 Chinese adults with overweight or obesity reported roughly 11% mean weight loss at the highest level tested over 24 weeks versus about 3% with placebo, alongside improvements in waist circumference, blood pressure, lipids, liver transaminases, and uric acid.
- Development is furthest advanced in China, where Phase 3 obesity and diabetes programs (the GLORY series) have been conducted.
Both are weekly dual GLP-1/glucagon agonists. Mazdutide is oxyntomodulin-derived and furthest along in China; survodutide is a Boehringer and Zealand molecule with a parallel MASH program.
- Investigational; not approved by the FDA or EMA.
- The most common adverse events were gastrointestinal (nausea, diarrhea, decreased appetite), most pronounced during escalation.
- Evidence outside Chinese populations and long-term outcome data remain limited.
Regulatory status
Mazdutide is investigational and not approved by the FDA or EMA. Its development is most advanced in China, where a regulatory filing for obesity/overweight has been pursued following Phase 3 results. Any use outside an authorized clinical trial is unapproved.
Investigational, currently in registered human clinical trials.
By the numbers
- 01Dual GLP-1 and glucagon receptor agonist derived from oxyntomodulin
- 02Developed by Innovent Biologics, licensed from Eli Lilly (LY3305677)
- 03Once-weekly subcutaneous injection (investigational)
- 04Phase 2 showed ~11% mean weight loss at 6 mg over 24 weeks
- 05Improved waist, blood pressure, lipids, liver enzymes and uric acid
- 06Most advanced in China; not FDA/EMA approved
Mazdutide: research formats
Choose the format you are researching to see route-specific notes.
Once-weekly subcutaneous injection; development is most advanced in China, with no FDA or EMA approval.
Mazdutide is an investigational once-weekly injectable dual GLP-1 and glucagon receptor agonist based on an oxyntomodulin analog, developed by Innovent Biologics under licence from Eli Lilly. It has progressed through Phase 3 in China but is not approved in the United States or Europe, so there is no US labeled presentation or titration schedule to reproduce.
Regulatory status differs by market. A filing or approval in one country does not create a labeled schedule that applies elsewhere, and this page does not reproduce non-US product labeling.
Use outside an authorized clinical trial is unapproved.
Sources
Every factual claim above resolves to a real, published source.
- A phase 2 randomised controlled trial of mazdutide in Chinese overweight adults or adults with obesityJi et al., Nature Communications, 2023 · PMID 38092790
- Mazdutide (IBI362 / LY3305677) clinical trials (PubMed search)PubMed search results
- Once-Weekly Mazdutide in Chinese Adults with Obesity or OverweightN Engl J Med, 2025 · PMID 40421736
- Mazdutide 9 mg in Chinese adults with a body mass index >=30 kg/m2 but without diabetes: A phase 2 randomized controlled trialMed, 2026 · PMID 41875890
- Comparative Efficacy and Safety of Glucagon Receptor Agonists on Metabolic Outcomes: A Network Meta-Analysis of Randomised Controlled TrialsEndocrinol Diabetes Metab, 2026 · PMID 41787737
- Registered mazdutide clinical trials (ClinicalTrials.gov search)ClinicalTrials.gov registry search
Cite this page
PepCue. “Mazdutide: the evidence.” PepCue, reviewed June 1, 2026. https://www.pepcue.app/p/mazdutide.
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