Written By: Abhinay Wadekar, BPharm
Reviewed By: Pharmacally Editorial Team
Innovent Biologics, Inc., announced landmark results from its fourth Phase 3 clinical trial, DREAMS-3, investigating mazdutide a dual GLP-1 and glucagon (GCG) receptor agonist in Chinese patients diagnosed with type 2 diabetes (T2D) and obesity. DREAMS-3 is the first multinational, head-to-head Phase 3 trial of a GCG/GLP-1 dual agonist against semaglutide in diabetes care, marking a major advance in next-generation metabolic therapeutics. The trial met its primary endpoint at week 32, 48.0% of mazdutide-treated participants achieved both HbA1c < 7.0% and ≥10% body weight reduction, outperforming semaglutide, which achieved the same target for only 21.0% of patients.
Mazdutide is developed by Innovent Biologics, Inc., a leading Chinese biopharmaceutical company specializing in innovative therapies for major diseases. Innovent holds the marketing rights for mazdutide in China, while Eli Lilly retains outside China global development rights, marking the program as a high-profile partnership.
About Mazdutide
Mazdutide (also known as IBI362 or LY3305677) is a novel molecule originally developed by Eli Lilly and licensed to Innovent Biologics for development and commercialization in China. It is a next-generation analog of oxyntomodulin (OXM), a naturally occurring peptide hormone that activates multiple metabolic pathways. Mazdutide design builds on prior peptide frameworks, including the Mastolide peptide, which establish the structural and functional basis for dual GLP-1 and glucagon receptor activation. Mazdutide’s development represents a significant advancement in peptide engineering as a new molecular entity designed to address multifactorial metabolic diseases including type 2 diabetes (T2D), obesity, and related comorbidities. After undergoing extensive preclinical optimization and multiple successful clinical phases globally and in China, mazdutide received marketing approval in China in June 2025 under the brand name Xinermei, becoming the first domestically approved dual GLP-1/glucagon receptor agonist for weight management and glycemic control.
Mazdutide acts as a once-weekly injectable dual agonist targeting both the glucagon-like peptide-1 (GLP-1) receptor and the glucagon (GCG) receptor. The GLP-1 receptor activation leads to improved insulin secretion, enhanced glucose regulation, and appetite suppression, contributing to improved glycemic control and weight loss. Simultaneously, glucagon receptor activation enhances energy expenditure by increasing hepatic fatty acid oxidation and thermogenesis, which further drives weight reduction. This balanced dual receptor stimulation provides multidimensional metabolic benefits beyond the effects seen with GLP-1-only agonists, including improvements in lipid profiles and serum uric acid levels, which address broader cardiometabolic risks. The combined action aims to deliver more robust and sustained weight loss and glycemic improvement in patients with T2D and obesity
Clinical Evidence: DREAMS-3
DREAMS-3 (NCT06184568) is a multi-center, randomized, open-label phase 3 trial the first globally to compare a GLP-1/GCG dual agonist head-to-head against semaglutide in T2D care. The trial enrolled 349 Chinese adults with early-stage T2D and obesity, inadequately controlled after lifestyle intervention ± metformin. Participants (mean age 42.4, mean baseline glycated hemoglobin [HbA1c] 8.02%, mean baseline weight 90.47 kg, and mean baseline BMI 32.98 kg/m²) received mazdutide 6 mg or semaglutide 1 mg for 32 weeks.
Trial Endpoints
The primary endpoint of the DREAMS-3 trial was the proportion of participants achieving both HbA1c < 7.0% and a reduction in body weight of ≥10% from baseline at week 32.
Secondary endpoints included the mean change in HbA1c from baseline and the mean percentage reduction in body weight at week 32. The study also evaluated additional metabolic biomarkers and safety outcomes.
Trial Results
At week 32, 48.0% of participants treated with mazdutide achieved the primary endpoint of HbA1c level less than 7.0% combined with more than 10% body weight reduction, compared to 21.0% in the semaglutide group (p < 0.0001), demonstrating clear superiority of mazdutide.
Secondary outcomes showed a mean HbA1c reduction of −2.03% in the mazdutide arm versus −1.84% with semaglutide. The average weight loss was 10.29% for mazdutide-treated patients compared to 6.00% in the semaglutide arm, with both differences reaching statistical significance (p < 0.05).
The extension phase of the trial allowed for longer-term dosing adjustments in participants continuing mazdutide treatment to optimize therapeutic benefits. The safety profile was consistent with prior studies, with no new safety signals detected and mostly mild to moderate gastrointestinal adverse events.
Safety Profile
Mazdutide safety profile remained consistent with earlier-phase data and class expectations. No new safety signals emerged; gastrointestinal symptoms (nausea, vomiting, diarrhea) were the most common adverse events, generally mild to moderate in severity and mostly occurring during dose titration. No increased risk for hypoglycemia or clinically significant liver/renal adverse events was observed in the DREAMS studies.
Key Opinions
Professor Ji Linong of Peking University People’s Hospital, the principal investigator, emphasized that the DREAMS-3 trial’s results mark a breakthrough in diabetes and obesity treatment, highlighting mazdutide significant effectiveness in managing both glycemic control and weight loss compared to existing therapies. Dr. Qian Lei, Chief R&D Officer at Innovent Biologics, expressed confidence that mazdutide dual receptor mechanism offers a transformative approach for patients with type 2 diabetes and obesity, reinforcing Innovent’s commitment to delivering innovative therapies that address complex metabolic diseases effectively.
Public Health Implications
Mazdutide offers significant advantages for Chinese patients with type 2 diabetes and obesity by effectively improving blood sugar control and reducing body weight, which are often difficult to manage together. Its superior performance compared to semaglutide sets a new standard for treating these interconnected conditions. By addressing multiple metabolic risk factors simultaneously, mazdutide has the potential to improve overall patient health and reduce complications linked to diabetes and obesity. Ongoing support from regulatory bodies and the continued partnership between Innovent and Eli Lilly could facilitate wider availability of mazdutide, expanding its benefits to more patient populations globally.
References
The DREAMS-3 Phase III clinical study of Masdutide, a head-to-head semaglutide trial, achieved its primary endpoint in dual efficacy in reducing blood sugar and weight, 28 Oct 2025, Innovent Biologics, https://www.innoventbio.com/#/news/651
A Study Comparing IBI362 vs Semaglutide in Chinese Adults with Early Type 2 Diabetes and Obesity, ClinicalTrials.gov ID NCT06184568,
https://clinicaltrials.gov/study/NCT06184568?intr=IBI362%20&rank=6
Ji L, et al, Safety and efficacy of a GLP-1 and glucagon receptor dual agonist mazdutide (IBI362) 9 mg and 10 mg in Chinese adults with overweight or obesity: A randomised, placebo-controlled, multiple-ascending-dose phase 1b trial. EClinicalMedicine, 2022 Oct 7; 54:101691, doi: 10.1016/j.eclinm.2022.101691. PMID: 36247927; PMCID: PMC9561728.