Mazdutide
Mazdutide is an investigational once-weekly peptide that activates both the GLP-1 and glucagon receptors, structurally related to the gut hormone oxyntomodulin. It has been studied in obesity and type 2 diabetes and is not approved in the US.
Overview
Mazdutide, known by the development codes LY3305677 and IBI362, is a dual agonist of the GLP-1 receptor and the glucagon receptor. It was originated by Eli Lilly and developed for Chinese markets by Innovent Biologics. Mazdutide is described as an analogue of oxyntomodulin, a naturally occurring peptide released from the gut alongside GLP-1 that weakly activates both receptors. By optimizing this dual activity and extending its duration, developers aimed to combine appetite suppression with increased energy expenditure.
Clinical development has included phase 2 and phase 3 trials in adults with overweight or obesity and in type 2 diabetes, largely conducted in China. These trials examined body weight, glycemic control, and markers such as liver fat. Mazdutide is part of the broader class of multi-receptor incretin agonists alongside survodutide, tirzepatide and retatrutide. In the US it is investigational and not approved.
Structure
Mazdutide is a synthetic peptide based on an oxyntomodulin-like sequence, which contains the full glucagon sequence with a C-terminal extension in the natural hormone. It incorporates amino acid substitutions to balance GLP-1 and glucagon receptor activity and to resist enzymatic degradation, and it carries a fatty acid side chain that promotes albumin binding for once-weekly dosing. Researchers should rely on patent and primary scientific literature for the exact sequence and modification.
Mechanism
Mazdutide activates the GLP-1 receptor, enhancing glucose-dependent insulin secretion, slowing gastric emptying and reducing appetite, and the glucagon receptor, which in the liver increases energy expenditure and fat oxidation. The combination is intended to produce greater weight loss and metabolic effects than GLP-1 receptor activation alone.
As with other dual agonists in this class, the GLP-1 component is thought to counteract the glucose-raising effect of glucagon receptor activation. The relative balance between the two activities differs among compounds such as mazdutide and survodutide, and its influence on clinical outcomes is still being characterized.
Research
Obesity trials
Phase 2 and phase 3 randomized trials in adults with overweight or obesity, mainly in China, evaluated mazdutide against placebo over periods of months. Investigators reported dose-related reductions in body weight, along with changes in waist circumference, blood pressure, lipids and liver fat. Gastrointestinal adverse events were the most common side effects. These trials provide the main clinical evidence base for the compound.
Type 2 diabetes
Trials in people with type 2 diabetes examined mazdutide's effects on HbA1c and body weight, including comparisons with placebo and with established GLP-1 receptor agonists. Reported results showed improvements in glycemic control and weight. The diabetes program, like the obesity program, has been conducted largely in Chinese populations, which should be considered when generalizing results. Some trials compared mazdutide with dulaglutide or other GLP-1 receptor agonists as active controls.
Liver and metabolic markers
Because glucagon acts directly on the liver, trials have reported changes in liver fat content measured by imaging and in liver enzymes. These secondary findings have prompted interest in mazdutide for fatty liver disease, but dedicated trials with histological endpoints are needed. Preclinical models also showed reductions in liver fat and body weight. Changes in liver fat measured by imaging are surrogate markers rather than clinical outcomes.
Evidence quality
Mazdutide has randomized phase 2 and phase 3 data, primarily from trials in China. Data from other populations, long-term safety and cardiovascular outcomes are more limited. In the US it remains investigational, and results should be interpreted within the context of the specific populations and trial designs studied. Head-to-head comparisons with other dual or triple agonists are limited, so relative efficacy is uncertain.
Regulatory status
Mazdutide is investigational and not approved in the US. It is not a recognized substance for US pharmacy compounding. Its regulatory status in other countries should be checked in current national sources. For sport, check the current WADA Prohibited List.
Status changes often. See the regulatory tracker for dated updates.
Quality and identity testing
A certificate of analysis for mazdutide should confirm identity by mass spectrometry with an expected mass that includes the lipidated side chain, and report reverse-phase HPLC purity. Key impurities include variants lacking or with altered side chains, deletion sequences and oxidation of susceptible residues; glucagon-derived sequences typically contain methionine and tryptophan, which oxidize readily. Aggregation should be assessed by size-exclusion chromatography. Because reference standards for investigational compounds are limited, the COA should state the sequence and modifications. Counter-ion and net peptide content should be reported.
For a walkthrough of each section of a certificate, see how to read a COA.
Storage and stability
Store lyophilized mazdutide sealed at -20 °C or colder, protected from light and moisture, and allow vials to reach room temperature before opening. Glucagon-related sequences are prone to fibrillation and oxidation in solution, and lipidation adds a tendency to self-associate, so solutions should be handled gently in low-binding containers. For lab use, keep solutions refrigerated for short-term work, aliquot for longer storage at -20 °C or below, and avoid repeated freeze-thaw cycles.
Download the Mazdutide data sheet (PDF): sequence, masses, expected MS ions and handling on one printable page.
Latest research
The newest PubMed-indexed papers that mention Mazdutide in their title or abstract, retrieved through Europe PMC and refreshed automatically. Inclusion is not an endorsement of a paper's findings.
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Frequently asked questions
What is oxyntomodulin and how does it relate to mazdutide?
Oxyntomodulin is a natural peptide hormone released from the gut after meals. It contains the full glucagon sequence plus a short extension and weakly activates both the glucagon and GLP-1 receptors. Mazdutide was designed as a long-acting oxyntomodulin analogue with optimized activity at both receptors.
Is mazdutide FDA approved?
No. Mazdutide is investigational and not approved in the US. It has been studied in phase 2 and phase 3 trials, mostly in China, in obesity and type 2 diabetes. Its status in other countries should be checked in current regulatory sources.
What is the difference between mazdutide and survodutide?
Both are once-weekly dual agonists of the GLP-1 and glucagon receptors. They were developed by different companies, mazdutide by Eli Lilly and Innovent Biologics and survodutide by Boehringer Ingelheim with Zealand Pharma, and they differ in sequence and in the balance of activity at each receptor. Their clinical programs have focused on somewhat different populations and indications.
Related compounds
- Survodutide
Survodutide is an investigational once-weekly peptide that activates both the glucagon and GLP-1 receptors. Developed by Boehringer Ingelheim, it has been studied in obesity and in metabolic dysfunction-associated steatohepatitis and is not approved in the US.
- Retatrutide
Retatrutide is an investigational once-weekly peptide that activates the GIP, GLP-1 and glucagon receptors. It is not FDA-approved; Eli Lilly plans a BLA submission in Q1 2027 after phase 3 results.
- Tirzepatide
Tirzepatide is a once-weekly peptide that activates both the GIP and GLP-1 receptors. It is FDA-approved for type 2 diabetes (Mounjaro) and chronic weight management (Zepbound).
- Semaglutide
Semaglutide is a long-acting glucagon-like peptide-1 (GLP-1) receptor agonist. It is FDA-approved for type 2 diabetes (Ozempic, Rybelsus) and chronic weight management (Wegovy).
References
- PubMed: all indexed literature on Mazdutide
- ClinicalTrials.gov: registered studies mentioning Mazdutide
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