Mazdutide

Mazdutide is a synthetic peptide derived from oxyntomodulin. It consists of 33 amino acids plus a fatty-acid side chain to extend its half-life.

Mazdutide acts as a dual agonist for the GLP-1 receptor and the glucagon receptor. Its purported benefits include significant weight loss, better glucose control, increased energy expenditure, and improvements in metabolic risk factors like liver fat, lipids, and waist circumference.

Mazdutide has shown very strong effects on weight loss in clinical trials. In a Phase 3 trial (GLORY-1) of Chinese adults with obesity, participants lost about 13.4 % of their body weight over 48 weeks on mazdutide, compared to virtually no change in the placebo group. A Phase 1 trial pushed doses up to 16 mg weekly in overweight adults and saw a ~20 % reduction in body weight, along with significant decreases in waist circumference. A meta-analysis combining several randomized trials found mazdutide reduced average body weight by roughly 6.2 % more than placebo ^{1, 2, 3}.

Mazdutide also improves metabolic markers. In people with type 2 diabetes and obesity, it outperformed semaglutide: nearly half of participants on mazdutide achieved both ≥ 10% weight loss and HbA1c below 7% by week 32. Animal studies in diabetic mice showed that mazdutide improved cognitive performance, enhanced brain structure, and activated pathways linked to energy metabolism and synaptic plasticity ^{4, 5}. In summary, mazdutide delivers substantial weight loss along with meaningful improvements in glucose control and metabolic-health markers.

Mazdutide’s main negative side effects, as shown in human clinical trials, are predominantly gastrointestinal. In a Phase 1 study up to 16 mg, the most common adverse events were nausea, vomiting, diarrhea, and constipation, and there was a notable increase in heart rate of over 10 beats per minute in many participants. In a Phase 2 trial in Chinese overweight or obese adults, diarrhea, nausea, and upper respiratory tract infections were the most frequent side effects ^{6, 7}. Also, In a randomized Phase 2 trial of mazdutide in Chinese patients with type 2 diabetes, 36% of those on the drug had diarrhea, 29% had decreased appetite, 23% had nausea, and 14% experienced vomiting; hypoglycemic episodes also increased with higher doses ⁸.

In a higher-dose Phase 1b study (9 mg–10 mg), there was a mean heart rate increase (up to +17 beats per minute), and mild ventricular extrasystoles in one participant ⁹. Furthermore, in a large NEJM-reported trial, mazdutide prompted sinus tachycardia in a small percentage of participants (2.0% at 4 mg; 4.5% at 6 mg), and mild elevations in liver enzymes (ALT/AST), lipase, and amylase were observed, though serious issues (like thyroid cancer) did not arise during the study ¹⁰. This profile indicates that while mazdutide is generally well tolerated, its main risks lie in gastrointestinal discomfort, modest cardiovascular stimulation (increased heart rate), and occasional lab abnormalities.

Mazdutide is a single peptide that agonizes both the glucagon-like peptide-1 receptor and the glucagon receptor, combining appetite-suppressing, insulinotropic effects with glucagon-driven increases in energy expenditure. Activation of GLP-1 receptors increases glucose-dependent insulin secretion and reduces food intake, while activation of glucagon receptors promotes hepatic glucose production and raises metabolic rate and lipolysis, producing greater net weight loss when both pathways are engaged. Clinical phase 2 trials and randomized studies report larger reductions in body weight and improved glycemic control with mazdutide compared with placebo, supporting the predicted complementary physiology of dual GLP-1/GCGR agonism. These trial results and mechanistic analyses are described in the phase 2 randomized trial and subsequent reviews of GLP-1/glucagon co-agonists ¹¹.

Mazdutide is currently not FDA-approved in the United States; rather, it remains a research-use only compound when offered here, because it has not completed the U.S. marketing approval process. Although mazdutide has shown efficacy in late-stage trials in other countries (such as China), and has been approved by foreign regulators, the FDA has not granted it marketing authorization, and it is considered an unapproved new drug under U.S. law. As for its status in sport, mazdutide belongs to the GLP-1 receptor agonist class, which is currently on WADA’s Monitoring Program. This means it is being monitored for potential misuse or performance effects, but it is not yet broadly prohibited under WADA rules. Importantly, athletic governing bodies vary in how they treat such peptides—some may impose stricter bans—so use in sport could carry risk depending on the specific organization.