Mazdutide

Mazdutide is a dual GLP-1 and glucagon receptor agonist approved in China for obesity treatment, promoting weight loss through appetite suppression, increased energy expenditure, and improved glycemic control.

Brief glance

The primary outcome is Weight Loss, but it's also used for Metabolic, Performance. This compound is considered a Peptide. It is also known as Maiyoute, Xin'ermei. It is not currently indicated as compoundable in 503A pharmacies. It is not listed under a DEA schedule.

Overview

Mazdutide is a dual agonist of the GLP-1 and glucagon receptors, developed as a once-weekly injectable for obesity and metabolic disorders. It promotes weight loss through GLP-1-mediated appetite suppression, slowed gastric emptying, and glucose-dependent insulin secretion, combined with glucagon-driven energy expenditure and hepatic lipid clearance. Phase 3 trials in Chinese adults with overweight or obesity have demonstrated up to 20.1% body weight reduction, alongside improved glycemic control and potential benefits for metabolic-associated steatotic liver disease.

Mazdutide is a dual agonist of the glucagon-like peptide-1 (GLP-1) receptor and glucagon receptor, developed as an investigational peptide therapeutic for obesity and metabolic diseases. The medication works through a dual-pathway mechanism that combines appetite suppression and reduced caloric intake via GLP-1 receptor activation with enhanced energy expenditure and hepatic fat metabolism through glucagon receptor stimulation. This dual-agonist approach distinguishes mazdutide from selective GLP-1 agonists and positions it for potentially greater weight loss and metabolic benefit in patients with obesity, type 2 diabetes, or metabolic-associated steatotic liver disease. Mazdutide is administered as a once-weekly injection and has received regulatory approval in China for chronic weight management, with Phase III clinical data demonstrating clinically relevant reductions in body weight and glycemic control.

Benefits

Mazdutide, a dual GLP-1 and glucagon receptor agonist, promotes significant weight reduction in adults with overweight or obesity, with clinical trials showing superior body weight loss compared to placebo at doses up to 9 mg weekly, alongside reductions in waist circumference and achievement of ≥5%, ≥10%, or ≥15% weight loss thresholds.¹,²,³ In patients with type 2 diabetes, it improves glycemic control by lowering HbA1c, fasting plasma glucose, and enhancing insulin sensitivity, while also reducing liver fat content.¹,⁴ Additional cardiometabolic benefits include decreases in systolic blood pressure, triglycerides, LDL cholesterol, total cholesterol, and ALT levels, supporting its role in managing obesity-related risk factors.¹,²,⁴

Side effects

The most common adverse effects of mazdutide are gastrointestinal disorders including diarrhea (36%), decreased appetite (29%), nausea (23%), vomiting (14%), and hypoglycemia (10%), which are typically mild to moderate, dose-dependent, and occur during dose titration.¹,⁴,⁵,⁶ These events predominate as expected for the GLP-1/glucagon receptor agonist class, with higher risks of nausea compared to placebo, alongside transient increases in heart rate, but low discontinuation rates and no unexpected safety signals in trials.²,⁴,⁵,⁶ Serious adverse events are rare and generally not attributed to the drug, such as isolated cases of myocardial ischemia or chronic sarcoidosis deemed unrelated.¹,⁴,⁶ Key safety considerations include contraindications or caution in patients with a history of pancreatitis, pregnancy, breastfeeding, or severe renal/hepatic impairment due to limited data in these populations.⁵ Long-term safety monitoring remains essential as ongoing studies evaluate extended use.¹

Mechanisms of action

Mazdutide acts as a dual agonist at the glucagon-like peptide-1 (GLP-1) receptor and the glucagon receptor (GCGR), mimicking the effects of endogenous incretin hormones and oxyntomodulin.⁷,⁸,⁹ Activation of the GLP-1 receptor stimulates glucose-dependent insulin secretion from pancreatic beta cells, suppresses glucagon release from alpha cells, slows gastric emptying, and reduces appetite via central nervous system signaling.⁷,⁸,¹⁰ Concurrent GCGR agonism promotes lipolysis in adipose tissue, enhances hepatic energy expenditure through thermogenesis and lipid oxidation, and increases basal metabolic rate, leading to synergistic improvements in glycemic control and body weight reduction.⁸,⁹,¹¹ This balanced dual-receptor mechanism distinguishes mazdutide from GLP-1 monotherapy agents, providing broader metabolic regulation.⁸,¹²