Moderate · humanPreprint
This Bayesian network meta-analysis systematically evaluated the dose-dependent efficacy and safety of mazdutide — a dual GLP-1 receptor and glucagon receptor agonist — in adults with obesity or overweight, with or without type 2 diabetes. Researchers searched five major databases through January 2026 and included nine randomized controlled trials comprising 2,292 participants. The study found that, compared with placebo, multiple mazdutide doses were associated with statistically significant improvements across a broad range of cardiometabolic outcomes, including body weight, waist circumference, BMI, HbA1c, fasting plasma glucose, blood pressure, LDL cholesterol, and liver enzymes (ALT). Subgroup analyses suggested that weight loss effects were more pronounced in non-diabetic individuals, while glycemic benefits were greater in those with type 2 diabetes. Gastrointestinal adverse events were notably more frequent with mazdutide relative to placebo, though serious adverse events were not significantly elevated. Key limitations include the relatively small number of included trials (n=9) and total participants, the indirect comparisons inherent to network meta-analysis methodology, potential heterogeneity across trial populations, and the preprint status of this work, meaning it has not yet undergone formal peer review.
Unknown journal · Jun 2026DOI ↗ Moderate · human
This phase 2 randomized, double-blind, placebo-controlled trial evaluated the efficacy and safety of mazdutide 9 mg — a once-weekly dual glucagon and glucagon-like peptide-1 (GLP-1) receptor agonist — in Chinese adults with obesity (BMI ≥30 kg/m²) without diabetes over 24 weeks. Eighty participants were randomized 3:1 to receive mazdutide 9 mg (n=60) or placebo (n=20). The primary endpoint was percentage change in body weight from baseline to week 24. The study found that participants receiving mazdutide 9 mg experienced a mean body weight reduction of approximately 12.78%, compared to a gain of 1.80% in the placebo group, representing a treatment difference of approximately −14.58% (95% CI: −18.00 to −11.16). The authors concluded that mazdutide 9 mg was safe and produced substantial weight reductions in this population. Key limitations include the relatively small sample size, the short 24-week duration, the single-country (China) population limiting generalizability, the phase 2 (exploratory) design, and industry sponsorship by Innovent Biologics. The findings are described as supportive of further clinical development.
Med (New York, N.Y.) · Mar 2026DOI ↗ Moderate · human
This meta-analysis pooled data from five randomised controlled trials to evaluate the efficacy and safety of mazdutide — a dual GLP-1 and glucagon receptor agonist — for weight management in non-diabetic adults with overweight or obesity. Searches were conducted across Cochrane Library, PubMed, Google Scholar, and ClinicalTrials.gov, and analyses were performed using random-effects models in RevMan 5.4. The pooled results reported by the study authors indicate that mazdutide was associated with significant reductions in percentage body weight (mean difference –12.42%), absolute body weight (–9.76 kg), and waist circumference (–7.98 cm) compared with control conditions. Secondary cardiometabolic outcomes — including systolic blood pressure (–7.68 mmHg), total cholesterol (–0.57 mmol/L), and LDL cholesterol (–0.37 mmol/L) — also showed reductions. Adverse events were slightly more frequent in the mazdutide groups (RR = 1.12), described as mild to moderate. A dose-wise meta-regression suggested a significant dose-dependent relationship. The authors acknowledge that findings are constrained by the small number of included trials (n = 5), which limits the robustness and generalisability of conclusions.
Diabetes, obesity & metabolism · Mar 2026DOI ↗ Moderate · human
This network meta-analysis systematically evaluated the comparative efficacy and safety of four investigational glucagon receptor agonist (GRA)-based agents — retatrutide, cotadutide, mazdutide, and survodutide — in adults with type 2 diabetes, overweight, or obesity. Researchers searched PubMed, Cochrane, Embase, and Scopus, ultimately including 14 randomised controlled trials analyzed using frequentist network meta-analysis with random-effects models. Key outcomes included absolute and percent body weight change, HbA1c reduction, adverse events, and treatment discontinuation due to adverse events. The study found that retatrutide produced the greatest absolute weight reduction versus placebo (MD −13.44 kg), followed by survodutide (MD −10.74 kg) and mazdutide (MD −6.47 kg); cotadutide's effect did not reach statistical significance. Retatrutide also showed the largest HbA1c reduction, though only its effect was statistically significant among the agents. Regarding tolerability, mazdutide demonstrated the most favorable safety profile, while retatrutide and cotadutide were associated with comparatively lower tolerability. The authors acknowledge limitations inherent to network meta-analysis, including reliance on early- and mid-phase trial data and the absence of direct head-to-head comparisons between agents.
Endocrinology, diabetes & metabolism · Mar 2026DOI ↗ Moderate · human
This Phase 3 randomized controlled trial evaluated mazdutide, a dual glucagon receptor (GCGR) and GLP-1 receptor (GLP-1R) agonist, as monotherapy versus placebo in 320 Chinese adults with type 2 diabetes (T2D) inadequately controlled by diet and exercise. Participants had a mean HbA1c of 8.24% and BMI of 28.2 kg/m². They were randomized 1:1:1 to weekly subcutaneous injections of mazdutide (4 mg or 6 mg) or placebo for 24 weeks, followed by a 24-week mazdutide extension phase. At week 24, the study found that both mazdutide doses significantly reduced HbA1c versus placebo (−1.57% and −2.15% for 4 mg and 6 mg, respectively, vs. −0.14% for placebo). Both doses also produced significantly greater body weight reductions and improved rates of composite endpoints (HbA1c <7.0% with ≥5% weight loss) compared to placebo. The most common adverse events—diarrhea, decreased appetite, and nausea—were consistent with the GLP-1R agonist class. Limitations include the single-ethnicity population (Chinese adults), the relatively short 24-week primary endpoint period, and the lack of an active comparator arm, which limits generalizability and comparative effectiveness conclusions.
Moderate · human
This Phase III randomized controlled trial evaluated mazdutide, a novel once-weekly dual glucagon and GLP-1 receptor agonist, compared to dulaglutide in 731 Chinese adults with type 2 diabetes (T2D) on background oral anti-diabetic therapy. Participants were randomized 1:1:1 to one of two mazdutide doses or dulaglutide (1.5 mg) for 28 weeks. The study found that both mazdutide doses demonstrated non-inferiority and superiority to dulaglutide in reducing HbA1c from baseline, with least-squares mean treatment differences of -0.24% and -0.30% for the lower and higher doses, respectively. Mazdutide also produced significantly greater reductions in body weight than dulaglutide, with differences of -3.78% and -5.76% for the two doses. The safety profile was generally acceptable, though gastrointestinal adverse events occurred more frequently with mazdutide than dulaglutide. Limitations include the relatively short 28-week duration, restriction to a Chinese population, and the lack of a placebo arm, which may limit generalizability of findings.
Moderate · humanPreprint
This meta-analysis pooled data from four randomized controlled trials (n = 918) to evaluate the efficacy of mazdutide — a dual GLP-1 and glucagon receptor agonist — in nondiabetic adults with overweight or obesity. Researchers searched PubMed, Scopus, and Web of Science and applied a random-effects model to analyze primary outcomes including body weight, BMI, and waist circumference, along with secondary cardiometabolic markers. The pooled analysis found that, compared with placebo, mazdutide was associated with statistically significant reductions in body weight (mean difference: −7.72 kg), BMI (−2.84 units), waist circumference (−5.76 cm), HbA1c (−0.30%), LDL cholesterol (−10.59 mg/dL), total cholesterol (−18.61 mg/dL), and triglycerides (−49.87 mg/dL). The authors concluded that mazdutide shows promise as a pharmacotherapy option for this population. Key limitations include the small number of included trials (n = 4), the relatively modest total sample size, the lack of long-term follow-up data, and the preprint status of this analysis, meaning it has not yet undergone formal peer review. Findings should therefore be interpreted with caution pending publication.
Unknown journal · Oct 2025DOI ↗