Mazdutide for Adults With Prediabetes: A Randomized, Double-Blind, Placebo-Controlled Trial (DREAM-PRE)

Summary

Prediabetes affects millions of adults worldwide and carries a high risk of progression to type 2 diabetes. Mazdutide is a once-weekly injectable drug that activates both GLP-1 and glucagon receptors, lowering blood sugar and body weight simultaneously. This study (DREAM-PRE) tests whether mazdutide can help adults with prediabetes return to normal blood sugar levels. Approximately 150 adults aged 18-75 years with prediabetes and BMI ≥22 kg/m² will be randomly assigned in equal numbers to one of three groups: mazdutide 4 mg once weekly, mazdutide 6 mg once weekly, or placebo once weekly. All participants also receive standardized diet and exercise guidance throughout the study. Treatment lasts 24 weeks, followed by 24 weeks of off-drug follow-up to see whether any benefits are maintained. The main question is: what proportion of participants achieve completely normal blood sugar (normal HbA1c, fasting glucose, AND glucose tolerance test) after 24 weeks of treatment? The study is conducted at approximately 10 hospitals across China.

Timeline

Start

2026-07

Primary completion

2028-06

Completion

2029-07

Publications

• Background Wilding JPH, Batterham RL, Calanna S, Davies M, Van Gaal LF, Lingvay I, McGowan BM, Rosenstock J, Tran MTD, Wadden TA, Wharton S, Yokote K, Zeuthen N, Kushner RF; STEP 1 Study Group. Once-Weekly Semaglutide in Adults with Overweight or Obesity. N Engl J Med. 2021 Mar 18;384(11):989-1002. doi: 10.1056/NEJMoa2032183. Epub 2021 Feb 10.
• Background Kahn SE, Deanfield JE, Jeppesen OK, Emerson SS, Boesgaard TW, Colhoun HM, Kushner RF, Lingvay I, Burguera B, Gajos G, Horn DB, Hramiak IM, Jastreboff AM, Kokkinos A, Maeng M, Matos ALSA, Tinahones FJ, Lincoff AM, Ryan DH; SELECT Trial Investigators. Effect of Semaglutide on Regression and Progression of Glycemia in People With Overweight or Obesity but Without Diabetes in the SELECT Trial. Diabetes Care. 2024 Aug 1;47(8):1350-1359. doi: 10.2337/dc24-0491.
• Background Pi-Sunyer X, Astrup A, Fujioka K, Greenway F, Halpern A, Krempf M, Lau DC, le Roux CW, Violante Ortiz R, Jensen CB, Wilding JP; SCALE Obesity and Prediabetes NN8022-1839 Study Group. A Randomized, Controlled Trial of 3.0 mg of Liraglutide in Weight Management. N Engl J Med. 2015 Jul 2;373(1):11-22. doi: 10.1056/NEJMoa1411892.
• Background Guo L, Zhang B, Xue X, Zhang X, Cai H, Jiang H, Zhang L, Jin P, Wang X, Cheng Z, Zhang S, Geng J, Guo Y, Hu H, Ma Q, Li L, Du H, Han-Zhang H, Xue F, Deng H, Qian L, Yang W; DREAMS-2 investigators. Mazdutide versus dulaglutide in Chinese adults with type 2 diabetes. Nature. 2026 Apr;652(8108):181-188. doi: 10.1038/s41586-025-10031-z. Epub 2025 Dec 17.
• Background Zhu D, Zhao J, Cai H, Chu X, Xiu S, Song C, Cheng Z, Cao H, Jiang H, Zhang L, Wang H, Shi B, Li Y, Liu M, Feng B, Xue F, Deng H, Li H, Li L, Li Y, Ma Q, Qian L. Mazdutide versus placebo in Chinese adults with type 2 diabetes. Nature. 2026 Apr;652(8108):174-180. doi: 10.1038/s41586-025-10026-w. Epub 2025 Dec 17.
• Background Wang L, Gao P, Zhang M, Huang Z, Zhang D, Deng Q, Li Y, Zhao Z, Qin X, Jin D, Zhou M, Tang X, Hu Y, Wang L. Prevalence and Ethnic Pattern of Diabetes and Prediabetes in China in 2013. JAMA. 2017 Jun 27;317(24):2515-2523. doi: 10.1001/jama.2017.7596.
• Background Gong Q, Zhang P, Wang J, Ma J, An Y, Chen Y, Zhang B, Feng X, Li H, Chen X, Cheng YJ, Gregg EW, Hu Y, Bennett PH, Li G; Da Qing Diabetes Prevention Study Group. Morbidity and mortality after lifestyle intervention for people with impaired glucose tolerance: 30-year results of the Da Qing Diabetes Prevention Outcome Study. Lancet Diabetes Endocrinol. 2019 Jun;7(6):452-461. doi: 10.1016/S2213-8587(19)30093-2. Epub 2019 Apr 26.
• Background Ji L, Jiang H, Cheng Z, Qiu W, Liao L, Zhang Y, Li X, Pang S, Zhang L, Chen L, Yang T, Li Y, Qu S, Wen J, Gu J, Deng H, Wang Y, Li L, Han-Zhang H, Ma Q, Qian L. A phase 2 randomised controlled trial of mazdutide in Chinese overweight adults or adults with obesity. Nat Commun. 2023 Dec 14;14(1):8289. doi: 10.1038/s41467-023-44067-4.
• Background Zhang B, Cheng Z, Chen J, Zhang X, Liu D, Jiang H, Ma G, Wang X, Gan S, Sun J, Jin P, Yi J, Shi B, Ma J, Ye S, Wang G, Ji L, Gu X, Yu T, An P, Deng H, Li H, Li L, Ma Q, Qian L, Yang W. Efficacy and Safety of Mazdutide in Chinese Patients With Type 2 Diabetes: A Randomized, Double-Blind, Placebo-Controlled Phase 2 Trial. Diabetes Care. 2024 Jan 1;47(1):160-168. doi: 10.2337/dc23-1287.

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Indications