Mazdutide
clinical trialsAlso known as: IBI362, LY3305677
**Mechanism of Action** Mazdutide (IBI362, LY3305677) is a synthetic peptide dual agonist of the glucagon-like peptide-1 (GLP-1) and glucagon receptors. By activating both pathways, it enhances insulin secretion, suppresses appetite, and delays gastric emptying via GLP-1 signaling, while glucagon receptor agonism increases energy expenditure and hepatic glucose production. This dual mechanism aims to achieve greater weight loss and glycemic control than GLP-1 receptor agonists alone, with potential additive effects on lipid metabolism and hepatic steatosis. **Key Research Findings** In Phase 2 trials (e.g., NCT04904913), mazdutide demonstrated dose-dependent reductions in body weight (up to 11.3% at 48 weeks at 6 mg) and HbA1c (mean reduction of 1.7% in type 2 diabetes patients) compared to placebo. Adverse events were predominantly gastrointestinal (nausea, vomiting), consistent with GLP-1-based therapies, with no unexpected safety signals. Phase 3 trials (e.g., GLORY-1, DREAM-1) are ongoing to confirm efficacy and long-term safety in obesity and type 2 diabetes populations. **Clinical Relevance** Mazdutide represents a promising next-generation incretin-based therapy for obesity and type 2 diabetes, potentially offering superior weight loss and metabolic benefits over selective GLP-1 agonists. If approved, it could address unmet needs in patients with obesity-related comorbidities, including non-alcoholic steatohepatitis (NASH). However, long-term cardiovascular outcome data and comparative effectiveness against existing therapies remain to be established. For research purposes only — not medical advice.
Key data
C207H317N45O65Research & studies
4 mg and 6 mg mazdutide were superior to 1.5 mg dulaglutide in reducing HbA1c (treatment difference: -0.24% and -0.30%, respectively).; Mazdutide led to significantly greater body weight reductions than dulaglutide (-3.78% for 4 mg, -5.76% for 6 mg).; More participants on mazdutide achieved the composite endpoint of HbA1c <7.0% and ≥5% weight loss at week 28.; Common adverse events with mazdutide included diarrhea, nausea, and vomiting, with higher gastrointestinal event rates than dulaglutide.
Novel agents target GLP-1, GIP, glucagon, amylin, and peptide YY receptors for synergistic metabolic benefits.; Maridebart cafraglutide combines GLP-1 receptor agonism with GIP receptor antagonism as an innovative approach.; Glucagon coagonists like survodutide and mazdutide show significant weight loss and improved glycemic control.; Orally active small-molecule GLP-1 receptor agonists such as danuglipron and orforglipron resist enzymatic degradation.
At week 32, mean weight loss was -10.09% with 4 mg mazdutide, -12.55% with 6 mg mazdutide, and +0.45% with placebo.; 73.9% (4 mg) and 82.0% (6 mg) of participants achieved ≥5% weight reduction at week 32 vs. 10.5% on placebo.; At week 48, weight loss was sustained: -11.00% (4 mg) and -14.01% (6 mg) vs. +0.30% on placebo.; Gastrointestinal adverse events were most common and mostly mild to moderate; discontinuation rates were low (≤1.5%).
Semaglutide and tirzepatide show consistent glucose and weight reduction across ethnicities, ages, and diabetes/obesity status.; Incretin therapies provide additive cardiovascular and renal protections beyond glycemic and weight control.; Emerging evidence suggests benefits for fatty liver disease, chronic inflammation, sleep apnea, and possibly cognitive decline.; New multi-targeting peptides include dual and triple receptor agonists, amylin combinations, and GIP antibody-based agents.
Frequently asked questions
What is Mazdutide?
**Mechanism of Action** Mazdutide (IBI362, LY3305677) is a synthetic peptide dual agonist of the glucagon-like peptide-1 (GLP-1) and glucagon receptors. By activating both pathways, it enhances insulin secretion, suppresses appetite, and delays gastric emptying via GLP-1 signaling, while glucagon receptor agonism incre
How does Mazdutide work?
GLP-1/glucagon dual receptor agonist in late-stage trials for obesity and type 2 diabetes.
What is the research status of Mazdutide?
Mazdutide is currently classified as clinical trials, with 42 research references on record. This is for research purposes only and is not medical advice.
What is the molecular weight of Mazdutide?
Mazdutide has a molecular weight of approximately 4476 g/mol (formula C207H317N45O65).
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