Mazdutide: Published Research

Introduction

Mazdutide (IBI362 / LY3305677) is a synthetic GLP-1R/GCGR dual agonist peptide that has progressed through phase 1b, phase 2, and phase 3 clinical study programs in Chinese adult populations with overweight, obesity, and type 2 diabetes. The depth and pace of this research program is notable: a phase 3 publication in The New England Journal of Medicine (May 2025) was followed within six months by back-to-back phase 3 publications in Nature. This article provides a bibliographic summary of the published primary research literature on mazdutide as of mid-2026, organized by study phase and indication. All findings are attributed to the cited source; this article does not draw independent conclusions about the compound's clinical utility.

Methodology Types in the Mazdutide Literature

The published research on mazdutide encompasses several study designs:

Phase 1b randomized controlled trials assessed safety, tolerability, pharmacokinetics, and early metabolic signals in ascending dose cohorts, typically over 12 weeks with additional follow-up.

Phase 2 randomized controlled trials assessed efficacy and safety over 24-week periods against placebo, providing dose-ranging data for phase 3 design.

Phase 3 randomized controlled trials — the GLORY program (weight management) and the DREAMS program (type 2 diabetes) — assessed efficacy and safety over 32- to 52-week periods against placebo or active comparators, including a head-to-head comparison with semaglutide. A parallel view of the phase 3 triple-receptor agonist program is available in the retatrutide published research article, which covers a related GLP-1/GIP/glucagon compound developed by Eli Lilly.

Preclinical and mechanistic studies have examined receptor binding, structural pharmacology, and organ-level signaling effects in in vitro and animal model systems. The molecular basis of these findings is covered in the mazdutide mechanism of action article.

Phase 1b Studies

Dose-Ascending Studies in Overweight and Obesity

Ji and colleagues (2021) published the first phase 1b study of IBI362 (LY3305677) in Chinese adults with overweight or obesity in eClinicalMedicine [1]. The randomized, placebo-controlled, multiple ascending dose study enrolled adults with overweight (BMI ≥ 24 kg/m²) accompanied by hyperphagia or at least one comorbidity, or obesity (BMI ≥ 28 kg/m²), across six centres in China, receiving once-weekly IBI362 across three dose cohorts or placebo for 12 weeks. The authors reported a safety profile described as similar to other GLP-1 receptor agonists and GLP-1-based co-agonists; at week 12, 41.7% of IBI362 recipients across dose cohorts demonstrated coincident reductions in body weight, LDL cholesterol, triglycerides, blood pressure, and serum uric acid, compared with none in the placebo group [1].

Ji and colleagues (2022) reported results from higher-dose cohorts of the phase 1b obesity/overweight study, published in eClinicalMedicine [2]. The authors reported that the mean percent change in body weight from baseline to week 12 was −11.7% in one cohort versus −1.8% in the placebo group, with a favorable safety profile [2].

Study in Type 2 Diabetes

Jiang and colleagues (2022) published a phase 1b randomized controlled trial of IBI362 in Chinese patients with type 2 diabetes in Nature Communications [3]. The study enrolled 43 participants randomized to receive once-weekly IBI362 across ascending dose cohorts, placebo, or open-label dulaglutide for 12 weeks. The authors described IBI362 as a "balanced once-weekly GLP-1 and glucagon receptor dual agonist" in the context of its pharmacological profile and reported favorable safety and tolerability [3].

Findings from research models do not establish safety or efficacy in humans. SpartaLabs makes no claims about the use of this compound.

Phase 2 Studies

Randomized Controlled Trial in Overweight and Obesity

Feng and colleagues (2023) published a phase 2 randomized controlled trial of mazdutide in Chinese overweight adults or adults with obesity in Nature Communications [4]. The study enrolled 248 participants randomized to mazdutide at three dose levels or placebo for 24 weeks, with percentage change from baseline in body weight as the primary endpoint. The authors reported that mazdutide at all three doses produced statistically significant reductions in body weight versus placebo at week 24. This publication was selected by Nature Communications as an Editor's Choice and included among 50 most important studies in translational and clinical research for the year [4].

Randomized Controlled Trial in Type 2 Diabetes

Shi and colleagues (2024) published results from a randomized, double-blind, placebo-controlled phase 2 trial of mazdutide in Chinese patients with type 2 diabetes in Diabetes Care [5]. The primary endpoint was change in HbA1c from baseline. The authors reported robust glycemic outcomes alongside reductions in body weight and cardiometabolic parameters, including liver enzyme markers and lipid values, and a favorable safety profile [5].

Phase 3 Studies

GLORY-1 Trial (Weight Management)

The GLORY-1 phase 3 trial was a randomized, double-blind, placebo-controlled study in Chinese adults with obesity or overweight with at least one obesity-related comorbidity, conducted over 48 weeks. Results were published in The New England Journal of Medicine in May 2025 [6]. The authors reported that participants receiving mazdutide at the higher studied dose achieved a mean body weight change of −14.84% from baseline compared with −0.47% for placebo, and both co-primary endpoints — percentage change in body weight at week 32 and proportion of participants achieving ≥5% body weight reduction at week 32 — were met for both mazdutide dose arms. The GLORY-1 publication supported the NMPA's June 2025 approval of mazdutide for chronic weight management in China [7].

GLORY-2 Trial (Higher-Dose Weight Management)

Innovent Biologics reported in August 2025 that the GLORY-2 phase 3 study at a higher dose met its primary and all key secondary endpoints in Chinese adults with obesity, with reported body weight reductions of up to 20.1% at 48 weeks [8]. Full peer-reviewed publication of GLORY-2 results was pending confirmation at the time this article was prepared.

DREAMS Program (Type 2 Diabetes)

Two phase 3 clinical studies — DREAMS-1 (mazdutide versus placebo) and DREAMS-2 (mazdutide as add-on to oral anti-diabetic agents versus comparator) — were published back-to-back in Nature in late 2025 [9]. Both studies reported statistically significant superiority versus comparators on glycemic control endpoints, alongside reductions in body weight and improvements in cardiometabolic and hepatic parameters. These results supported the NMPA's September 2025 approval of mazdutide for glycemic control in type 2 diabetes.

DREAMS-3 represented the first phase 3 trial in the GCG/GLP-1 dual receptor agonist class to include a head-to-head comparison with semaglutide in type 2 diabetes. Results reported at scientific meetings indicated statistically significant superiority of mazdutide on the composite primary endpoint of HbA1c < 7.0% combined with ≥10% body weight reduction at week 32, versus semaglutide [9]. Peer-reviewed publication was pending confirmation at the time of writing.

Preclinical and Mechanistic Research

Peng and colleagues (2025) published a multi-omics preclinical study in eBioMedicine examining mazdutide's effects on cognitive function in a db/db mouse model of diabetic encephalopathy [10]. The study reported differential effects on synaptic markers, neuroinflammatory pathways, and energy metabolism gene expression in mazdutide-treated versus dulaglutide-treated animals. The clinical relevance of these animal model findings is not established.

Zhou and colleagues (2023) published cryo-electron microscopy structures of GLP-1R and GCGR in complex with heterotrimeric Gs protein and GLP-1R/GCGR dual agonist peptides in the Proceedings of the National Academy of Sciences [11]. While this study did not include mazdutide specifically, the structural insights into the dual-agonism binding geometry at class B1 GPCRs provide relevant mechanistic context for the compound class.

Active Research Frontiers

Several areas of the mazdutide research program are under active investigation. Long-term cardiovascular outcomes data have not been published, though dedicated cardiovascular outcomes trials are standard for this compound class and have been discussed in the clinical community. Research-grade Mazdutide from SpartaLabs is supplied with batch-specific Certificates of Analysis for non-clinical investigation. Research in non-Chinese populations is ongoing: Eli Lilly has reported US-based phase 2 investigation of mazdutide, with results not yet available in peer-reviewed form at the time this article was prepared. The mechanistic contribution of GCGR versus GLP-1R engagement to each observed outcome in human clinical studies — and the compound's pharmacological profile in populations without significant hepatic or metabolic comorbidities — represent areas of continuing inquiry.

References

1. Ji L, Jiang H, Shi W, Wang H, Cheng Z, Pan T, et al. IBI362 (LY3305677), a weekly-dose GLP-1 and glucagon receptor dual agonist, in Chinese adults with overweight or obesity: a randomised, placebo-controlled, multiple ascending dose phase 1b study. eClinicalMedicine. 2021;40:101088. PMCID: PMC8374649. DOI: 10.1016/j.eclinm.2021.101088

2. Ji L, Luo X, Shi W, Wang H, Cheng Z, Pan T, 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;53:101691. PMCID: PMC9561728. DOI: 10.1016/j.eclinm.2022.101691

3. Jiang H, Pang S, Zhang Y, Liu J, Chen Y, Yang L, et al. A phase 1b randomised controlled trial of a glucagon-like peptide-1 and glucagon receptor dual agonist IBI362 (LY3305677) in Chinese patients with type 2 diabetes. Nat Commun. 2022;13(1):3613. PMCID: PMC9232612. DOI: 10.1038/s41467-022-31328-x

4. Feng Z, Zhao C, Wang X, Gan L, Xia L, Han C, et al. A phase 2 randomised controlled trial of mazdutide in Chinese overweight adults or adults with obesity. Nat Commun. 2023;14(1):8156. DOI: 10.1038/s41467-023-44067-4

5. Shi W, Zhou X, Zhang D, Zou Y, Liu Y, Li X, et al. Efficacy and safety of mazdutide in Chinese patients with type 2 diabetes: a randomized, double-blind, placebo-controlled phase 2 trial. Diabetes Care. 2024;47(1):160-168. DOI: 10.2337/dc23-1287

6. Innovent Biologics / GLORY-1 investigators. Phase 3 clinical study of mazdutide in Chinese adults with overweight or obesity (GLORY-1). N Engl J Med. 2025;392(22):2215-2225. DOI: 10.1056/NEJMoa2411528

7. Innovent Biologics, Inc. Innovent announces mazdutide, first dual GCG/GLP-1 receptor agonist, received approval from China's NMPA for chronic weight management. Press release. June 27, 2025. Available at: https://www.prnewswire.com/news-releases/innovent-announces-mazdutide-first-dual-gcgglp-1-receptor-agonist-received-approval-from-chinas-nmpa-for-chronic-weight-management-302493152.html

8. Innovent Biologics, Inc. Mazdutide 9 mg achieves up to 20.1% weight loss in Chinese adults with obesity, GLORY-2 study meets primary and all key secondary endpoints. Press release. August 2025. Available at: https://www.prnewswire.com/news-releases/mazdutide-9-mg-achieves-up-to-20-1-weight-loss-in-chinese-adults-with-obesity-glory-2-study-meets-primary-and-all-key-secondary-endpoints-302620471.html

9. Innovent Biologics, Inc. Nature — Two phase 3 clinical results of mazdutide (GLP-1/GCG dual receptor agonist) in Chinese adults with type 2 diabetes have been back-to-back published in Nature. Press release. December 2025. Available at: https://www.prnewswire.com/news-releases/nature--two-phase-3-clinical-results-of-mazdutide-glp-1gcg-dual-receptor-agonist-in-chinese-adults-with-type-2-diabetes-have-been-back-to-back-published-in-nature-302644606.html

10. Peng J, Li M, Zhao Z, Wang R, Huang Y, Zhang H, et al. Mazdutide, a dual agonist targeting GLP-1R and GCGR, mitigates diabetes-associated cognitive dysfunction: mechanistic insights from multi-omics analysis. eBioMedicine. 2025;107:105791. PMID: 40479843. DOI: 10.1016/j.ebiom.2025.105791

11. Zhou F, Zhang H, Cong Z, Zhao F, Zhao L, Cai X, et al. Structural analysis of the dual agonism at GLP-1R and GCGR. Proc Natl Acad Sci USA. 2023;120(35):e2303696120. PMCID: PMC10438375. DOI: 10.1073/pnas.2303696120

12. [Case report — adolescent with obesity, type 2 diabetes, and hyperuricemia.] Mazdutide case report. Front Endocrinol. 2025. PMCID: PMC12477040. Available at: https://pmc.ncbi.nlm.nih.gov/articles/PMC12477040/