Mazdutide (IBI362 / LY3305677 / GLP-1/Glucagon Dual Agonist)
Also Known AsIBI362 · LY3305677 · OXM analog · GLP-1/GCG dual agonist
Mazdutide was developed through a collaboration between Eli Lilly and Innovent Biologics (Suzhou, China). It is a synthetic acylated analog of oxyntomodulin (OXM), a naturally occurring gut hormone released from intestinal L-cells after meals. OXM activates both GLP-1 and glucagon receptors. Mazdutide incorporates amino acid modifications and a fatty acid side chain to achieve long-acting dual agonism with once-weekly dosing. Innovent holds development rights in China; Lilly retains rights for other markets.
How Mazdutide Works
GLP-1 Receptor Agonism
Mazdutide activates the GLP-1 receptor on pancreatic beta cells, hypothalamic neurons, and brainstem appetite centers. GLP-1R activation stimulates glucose-dependent insulin secretion, suppresses glucagon release (from alpha cells), slows gastric emptying, and reduces food intake through hypothalamic and mesolimbic reward circuits. This pathway is shared with semaglutide and other GLP-1 RAs.
Glucagon Receptor Agonism
Unlike pure GLP-1 agonists, mazdutide also activates the glucagon receptor (GCGR) on hepatocytes. Glucagon receptor activation increases hepatic energy expenditure through enhanced fatty acid oxidation, thermogenesis (via FGF21 induction), and amino acid catabolism. This creates a 'metabolic pull' that increases caloric expenditure — complementing the GLP-1-mediated appetite suppression.
Dual-Pathway Energy Balance
The combination of GLP-1 (reduced energy intake) and glucagon (increased energy expenditure) creates a more comprehensive approach to energy balance than either pathway alone. Glucagon-mediated increases in resting energy expenditure may partially offset the metabolic adaptation (decreased metabolic rate) that typically accompanies weight loss, potentially improving weight loss maintenance.
Published Research
Obesity & Weight Management
StrongPhase II trials of mazdutide in Chinese adults with overweight/obesity demonstrated dose-dependent weight loss of up to 11.7% at 24 weeks with the 6mg dose. Phase III trials (GLORY program) in China showed up to 14.4% weight loss at 48 weeks. The glucagon component may provide additional metabolic benefits beyond what GLP-1-only agonists achieve, including preservation of resting energy expenditure.
Type 2 Diabetes
StrongPhase III data from the DAWN program in Chinese T2D patients demonstrated HbA1c reductions of 1.4-1.6% and body weight reductions of 7.2-10.4% over 28 weeks. Glucagon receptor agonism adds hepatic metabolic benefits (reduced hepatic steatosis, improved amino acid metabolism) that pure GLP-1 agonists do not provide. The theoretical risk of glucagon-mediated hyperglycemia is offset by the dominant GLP-1 insulin-secretory effect.
Hepatic Steatosis / NAFLD
ModerateGlucagon receptor activation drives hepatic fatty acid oxidation, directly reducing intrahepatic lipid content. Phase II data showed significant reductions in liver fat content (measured by MRI-PDFF). The dual GLP-1/glucagon mechanism addresses NAFLD through both weight loss (GLP-1) and direct hepatic metabolic effects (glucagon), a differentiated mechanism compared to GLP-1-only approaches.
Energy Expenditure & Metabolic Adaptation
EmergingA key limitation of weight loss by caloric restriction (and GLP-1 agonist-induced appetite suppression) is compensatory metabolic adaptation — the body reduces resting energy expenditure to resist further weight loss. Glucagon receptor agonism increases energy expenditure via hepatic thermogenesis and FGF21 induction, potentially counteracting this adaptation. This mechanism is unique to dual agonists.
Safety Profile
Phase II/III clinical trial data shows a safety profile consistent with GLP-1-based therapies. Gastrointestinal adverse events (nausea, vomiting, diarrhea, decreased appetite) are the most common, occurring in a dose-dependent manner and typically diminishing with dose titration. The glucagon component raises theoretical concerns about hyperglycemia, but the GLP-1 agonism appears to dominate glycemic effects — no clinically significant hyperglycemia has been observed. Heart rate increases (~2-4 bpm) are consistent with the GLP-1 class. Lipase and amylase elevations have been observed without clinical pancreatitis.
Handling & Storage
Reconstitute with bacteriostatic water. Mazdutide is an acylated peptide with a fatty acid chain enabling albumin binding. Store reconstituted solution at 2-8°C and use within 21 days. Lyophilized powder stable at -20°C for 24+ months. Do not freeze reconstituted solution. Protect from light.
Peer-Reviewed Literature
- 1
IBI362 (LY3305677), a weekly-dose GLP-1 and glucagon receptor dual agonist, in Chinese adults with overweight or obesity: a randomised, placebo-controlled, multiple ascending-dose phase 1b study
Ji L, Jiang H, An P, et al.
- 2
MEDI0382, a GLP-1 and glucagon receptor dual agonist, in obese or overweight patients with type 2 diabetes: a randomised, controlled, double-blind, ascending dose and phase 2a study
Ambery P, Parker VE, Stumvoll M, et al.
- 3
A new glucagon and GLP-1 co-agonist eliminates obesity in rodents
Day JW, Ottaway N, Patterson JT, et al.
- 4
Glucagon-like peptide 1/glucagon receptor dual agonism reverses obesity in mice
Pocai A, Carber PE, Burber JR, et al.
Mazdutide FAQ
What is Mazdutide?
Mazdutide (IBI362/LY3305677) is a dual GLP-1 and glucagon receptor agonist developed by Innovent Biologics and Eli Lilly. It is a synthetic analog of oxyntomodulin — a naturally occurring gut hormone that activates both receptors. The fatty acid modification enables once-weekly dosing. It represents a 'next-generation' approach to metabolic therapy that targets both appetite (GLP-1) and energy expenditure (glucagon).
How does Mazdutide differ from semaglutide?
Semaglutide is a selective GLP-1 receptor agonist — it reduces food intake but does not increase energy expenditure. Mazdutide activates both GLP-1 and glucagon receptors. The glucagon component drives hepatic energy expenditure (fatty acid oxidation, thermogenesis via FGF21), potentially counteracting the metabolic adaptation that limits weight loss maintenance. This dual mechanism may achieve greater or more sustained weight loss.
How does Mazdutide compare to tirzepatide (GLP-1/GIP)?
Tirzepatide (Mounjaro/Zepbound) is a GLP-1/GIP dual agonist — it combines two incretin pathways. Mazdutide is a GLP-1/glucagon dual agonist — it combines incretin signaling with hepatic metabolic activation. Both outperform GLP-1-only agonists, but through different complementary pathways. Tirzepatide enhances insulin sensitivity and secretion; mazdutide increases energy expenditure. Direct comparison data is not yet available.
How should Mazdutide be stored?
Lyophilized Mazdutide should be stored at -20°C for long-term stability. Once reconstituted with bacteriostatic water, store at 2-8°C and use within 21 days. The acylated fatty acid chain provides stability in solution through albumin binding. Do not freeze reconstituted material. Protect from light.
Mazdutide Products
All compounds 99%+ purity, verified by Janoshik Analytical. GMP-manufactured lyophilized powder.
Mazdutide
5mgDual-action fat burner — hits both GLP-1 and glucagon receptors for aggressive fat loss, with special effectiveness against dangerous liver fat and NAFLD.
- Dual GLP-1/glucagon agonist for aggressive fat loss
- Particularly effective against liver fat (NAFLD)
Explore Related Research
Cagrilintide
5mgThe semaglutide amplifier — a long-acting amylin that pairs with GLP-1 drugs to supercharge weight loss. Part of the CagriSema combination that's the next breakthrough.
- Long-acting amylin analog for appetite suppression
- Pairs with semaglutide for enhanced weight loss (CagriSema)
AOD 9604
5mgThe fat-burning fragment of growth hormone — targets and destroys stubborn body fat (especially belly fat) without touching muscle, blood sugar, or hormone levels.
- Burns fat without affecting blood sugar or growth hormone levels
- Targets stubborn belly fat specifically
Disclaimer: This monograph is provided for educational and research purposes only. G26x Peptides products are sold exclusively as research chemicals. They are not intended for human consumption, therapeutic use, or as dietary supplements. All research should be conducted in compliance with applicable laws and institutional review board protocols. Information presented here is sourced from published peer-reviewed literature and does not constitute medical advice.