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

NCT07654062 | Not Yet Recruiting Phase 4 DMC

• 2 other identifiers: DREAM-PRE-IIT-2026SWYX:NO. 2026-1026
• Study Type: interventional
• Target: 150
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Impaired Fasting Glucose; Impaired Glucose Tolerance (Prediabetes); Prediabetes

Keywords

Mazdutide; IBI362; GLP-1R/GCGR dual agonist; Prediabetes; Diabetes prevention; Normal glucose regulation; Beta-cell function; Insulin resistance; Weight loss

Outcome Measures

Primary Outcomes (1)

• Proportion of Participants Achieving Normal Glucose Regulation (NGR) at Week 24

  NGR is defined as simultaneous achievement of all three criteria: HbA1c \<5.7%, fasting plasma glucose \<6.1 mmol/L, and 75g OGTT 2-hour plasma glucose \<7.8 mmol/L, assessed by central laboratory. Missing data imputed by non-responder imputation (NRI). Fixed sequential testing: mazdutide 6 mg vs. placebo first, then mazdutide 4 mg vs. placebo (two-sided alpha=0.05, CMH test stratified by site).

  Week 24

Secondary Outcomes (29)

• Change from Baseline in HbA1c

  Week 24 and Week 48

• Change from Baseline in Fasting Plasma Glucose

  Week 24 and Week 48

• Change from Baseline in OGTT 2-Hour Plasma Glucose

  Week 24 and Week 48

• IFG Remission Rate (FPG <6.1 mmol/L)

  Week 24 and Week 48

• IGT Remission Rate (OGTT 2h-PG <7.8 mmol/L)

  Week 24 and Week 48

Other Outcomes (6)

• Difference in Proportion of Participants Achieving NGR Between Mazdutide 6 mg and 4 mg Arms at Week 24

  Week 24 and Week 48

• NGR Rate at Week 24 by Baseline Prediabetes Type (IFG Only, IGT Only, IFG+IGT, or Elevated HbA1c Only)

  Week 24 and Week 48

• NGR Rate at Week 24 by Baseline BMI Subgroup (<28 vs ≥28 kg/m²)

  Week 24 and Week 48

Study Arms (3)

Mazdutide 4 mg

EXPERIMENTAL

Mazdutide 2 mg once weekly subcutaneous injection for 4 weeks (titration), then 4 mg once weekly for 20 weeks. All participants receive standardized lifestyle intervention (dietary modification and aerobic exercise) throughout the 48-week study period.

Drug: Mazdutide; Behavioral: Standardized Lifestyle Intervention

Mazdutide 6 mg

EXPERIMENTAL

Mazdutide 2 mg once weekly subcutaneous injection for 4 weeks, then 4 mg once weekly for 4 weeks, then 6 mg once weekly for 16 weeks. All participants receive standardized lifestyle intervention throughout the 48-week study period.

Drug: Mazdutide; Behavioral: Standardized Lifestyle Intervention

Placebo

PLACEBO COMPARATOR

Matching placebo once weekly subcutaneous injection. Placebo pens are identical to active drug pens in appearance, color, volume, and packaging. The titration schedule mirrors the 6 mg arm (weeks 0-4, 5-8, 9-24) to maintain blinding. All participants receive standardized lifestyle intervention throughout the 48-week study period.

Drug: Placebo; Behavioral: Standardized Lifestyle Intervention

Interventions

Mazdutide DRUG

GLP-1 receptor/glucagon receptor (GLP-1R/GCGR) dual agonist, administered by subcutaneous injection once weekly using a pre-filled pen device. Arm 1 (4 mg): titration from 2 mg QW (weeks 0-4) to 4 mg QW (weeks 5-24). Arm 2 (6 mg): titration from 2 mg QW (weeks 0-4) to 4 mg QW (weeks 5-8) to 6 mg QW (weeks 9-24). Injection sites: abdomen, anterior-lateral thigh, or lateral upper arm, rotated at each injection.

Mazdutide 4 mg; Mazdutide 6 mg

Placebo DRUG

Matching placebo for mazdutide, administered by subcutaneous injection once weekly using a pre-filled pen device identical in appearance, color, volume, and packaging to the active drug pen. Titration schedule mirrors the 6 mg mazdutide arm to maintain blinding.

Placebo

Standardized Lifestyle Intervention BEHAVIORAL

Structured dietary modification with an energy deficit of 500-750 kcal/day and moderate-intensity aerobic exercise of at least 150 minutes per week, maintained throughout the 48-week study period. Applied equally to all three arms.

Mazdutide 4 mg; Mazdutide 6 mg; Placebo

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Voluntarily signed written informed consent prior to any study procedures
• Age 18 to 75 years (inclusive) at the time of signing informed consent; male or female
• Prediabetes confirmed by central laboratory at screening, meeting at least one of the following criteria per Chinese Diabetes Society (CDS) standards, and not meeting diagnostic criteria for diabetes:
• Impaired Glucose Tolerance (IGT): 75g OGTT 2-hour plasma glucose
• mmol/L and \<11.1 mmol/L
• Impaired Fasting Glucose (IFG): fasting plasma glucose ≥6.1 mmol/L and \<7.0 mmol/L
• Elevated HbA1c: 5.7% ≤ HbA1c \< 6.5% (39-48 mmol/mol)
• BMI ≥22.0 kg/m² at screening
• Self-reported body weight change \<10% within 3 months prior to screening; not currently participating in any organized weight-loss program
• Able to understand study requirements, complete all planned visits and examinations, self-administer once-weekly subcutaneous injections, and use the study app for daily monitoring

You may not qualify if:

• Continuous use of any antidiabetic medication for more than 7 days within 3 months prior to screening, including: biguanides (metformin), alpha-glucosidase inhibitors (acarbose, voglibose, miglitol), sulfonylureas (glimepiride, gliclazide, glipizide, glibenclamide), glinides (repaglinide, nateglinide), thiazolidinediones (pioglitazone, rosiglitazone), DPP-4 inhibitors (sitagliptin, saxagliptin, vildagliptin, linagliptin, alogliptin), SGLT2 inhibitors (dapagliflozin, empagliflozin, canagliflozin, ertugliflozin), insulin (any formulation), or traditional Chinese medicine with confirmed glucose-lowering indication.
• Use of any of the following within 6 months prior to screening (regardless of duration): GLP-1 receptor agonists (semaglutide, liraglutide, dulaglutide, exenatide, lixisenatide, benaglutide, etc.), GIP/GLP-1 dual agonists (tirzepatide, etc.), any dual or triple agonist containing GLP-1R and/or GCGR components (including mazdutide), or any GLP-1 class investigational drug in clinical development.
• Use of any prescription weight-loss medication within 3 months prior to screening (regardless of duration), including orlistat, naltrexone/bupropion combination, phentermine/topiramate combination, or any weight-loss drug approved in China or in clinical development. Over-the-counter dietary supplements are not excluded but must be recorded.
• Spontaneous body weight change ≥10% within 3 months prior to screening (based on self-report and/or available medical records), or currently participating in any organized weight-loss program (including commercial weight-loss plans or weight-loss interventions in other clinical trials).
• Prior bariatric or metabolic surgery including Roux-en-Y gastric bypass, sleeve gastrectomy, adjustable gastric banding, biliopancreatic diversion, intragastric balloon placement, or other bariatric surgery.
• Prior history of acute pancreatitis (confirmed by imaging or surgery) or chronic pancreatitis; or serum amylase \>3× ULN or serum lipase \>3× ULN at screening.
• Personal history of medullary thyroid carcinoma (MTC) or multiple endocrine neoplasia type 2 (MEN2); first-degree family history of MTC or MEN2; or serum calcitonin ≥50 ng/L at screening.
• Any of the following within 6 months prior to screening: acute myocardial infarction (STEMI or NSTEMI), ischemic or hemorrhagic stroke, transient ischemic attack (TIA), coronary revascularization (PCI or CABG), or hospitalization for unstable angina.
• Clinically significant arrhythmia on 12-lead ECG at screening, including:
• Mobitz Type II or third-degree atrioventricular block, sustained ventricular tachycardia (≥30 seconds or requiring cardioversion), QTcF \>500 ms, or resting heart rate \<50 bpm (in subjects not using beta-blockers or calcium channel blockers).
• Uncontrolled hypertension: confirmed mean systolic blood pressure ≥180 mmHg and/or mean diastolic blood pressure ≥110 mmHg on repeated measurements at screening despite antihypertensive therapy. Subjects with controlled blood pressure on a stable antihypertensive regimen (stable for ≥4 weeks prior to screening) are allowed to enroll.
• ALT \>3× ULN, AST \>3× ULN, or total bilirubin \>2× ULN at screening (except confirmed Gilbert's syndrome with normal direct bilirubin).
• eGFR (CKD-EPI) \<45 mL/min/1.73 m² at screening. Subjects with eGFR 45-60 mL/min/1.73 m² may enroll with enhanced renal function monitoring.
• Any of the following gastrointestinal conditions: known gastroparesis (confirmed by gastric emptying study or clinical diagnosis), inflammatory bowel disease (Crohn's disease or ulcerative colitis, active or remission), short bowel syndrome, prior gastrointestinal surgery likely to affect drug absorption (excluding simple appendectomy and laparoscopic cholecystectomy), or other serious gastrointestinal disease likely to significantly affect drug tolerability or absorption.
• Diagnosis or active treatment of any malignancy within 5 years prior to screening.

Sponsors & Collaborators

• Shandong Provincial Hospital: lead
• Innovent Biologics, Inc.: collaborator

Study Sites (1)

Shandong Provincial Hospital Affiliated to Shandong First Medical University

Jinan, Shandong, 250021, China

Location

Related Publications (9)

• 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.

  PMID: 33567185 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.

  PMID: 38907683 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.

  PMID: 26132939 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.

  PMID: 41407860 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.

  PMID: 41407859 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.

  PMID: 28655017 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.

  PMID: 31036503 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.

  PMID: 38092790 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.

  PMID: 37943529 BACKGROUND

MeSH Terms

Conditions

Prediabetic State; Glucose Intolerance; Insulin Resistance; Weight Loss

Interventions

mazdutide

Condition Hierarchy (Ancestors)

Diabetes Mellitus; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases; Hyperglycemia; Hyperinsulinism; Body Weight Changes; Body Weight; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Study Officials

• Jiajun Zhao, MD, PhD

  Shandong Provincial Hospital

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Jiajun Zhao, MD, PhD

CONTACT

0531-68776025; jjzhao@sdu.edu.cn

Xiude Fan, MD, PhD

CONTACT

+8613186067538; fanxiudexjtu@163.com

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER GOV
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor, Chief Physician, Department of Endocrinology and Metabolic Disease

Study Record Dates

• First Submitted: June 4, 2026
• First Posted: June 17, 2026
• Study Start (Estimated): July 1, 2026
• Primary Completion (Estimated): June 1, 2028
• Study Completion (Estimated): July 1, 2029
• Last Updated: June 17, 2026

Record last verified: 2026-06

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)