PrediabetesPhase 4DREAM-PRENCT07654062

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

A Phase 4 study testing Mazdutide and Standardized Lifestyle Intervention in people with Prediabetes and Impaired Fasting Glucose, run by Shandong Provincial Hospital at 1 site in China.

Not yet recruiting

Opening soon. The study is approved but enrolment has not started yet. Sites may already take enquiries.

Sites and contacts

Official record

Search all trials

Trial 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. Read more about this study

Who is it for?: Ages 18 to 75 years
Conditions the study is for: Prediabetes, Impaired Fasting Glucose, Impaired Glucose Tolerance (Prediabetes)
What is being tested?: Mazdutide and Standardized Lifestyle Intervention
Type of treatment: Injection or infusion, Lifestyle or therapy programme
Could I receive a placebo?: Yes, some participants may receive a placebo
How many people: 150 participants
Where: 1 siteChina
Study dates: Jul 2026to Jul 2029
Phase: Phase 4
Are there results?: Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 to 75 years
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

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
7.8 mmol/L and <11.1 mmol/L
Impaired Fasting Glucose (IFG): fasting plasma glucose ≥6.1 mmol/L and <7.0 mmol/L

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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

Who cannot join

Confirmed diabetes at screening (FPG ≥7.0 mmol/L, OGTT 2h-PG ≥11.1 mmol/L, or HbA1c ≥6.5%); or prior confirmed diagnosis of type 1 diabetes, type 2 diabetes, or other specific types of diabetes. Prior gestational diabetes in whom blood glucose has returned to prediabetes levels after delivery is NOT grounds for exclusion.
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.

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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.
NYHA Class III or IV heart failure. (NYHA Class I and II are not grounds for exclusion.)
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.
Positive urine pregnancy test at screening, currently breastfeeding, or planning pregnancy during the 48-week study period.
Known allergy to mazdutide or any excipient in its formulation; or prior serious allergic reaction to any GLP-1 class drug (defined as angioedema, anaphylactic shock, or allergic reaction requiring hospitalization).
Participation in any other interventional clinical trial within 3 months prior to screening (excluding purely observational or epidemiological studies not involving investigational drugs or devices), or currently enrolled in any other clinical trial.
Currently on long-term systemic corticosteroids (expected continuous use >14 days, oral or intravenous); or currently using drugs known to significantly affect body weight or glucose metabolism that cannot be discontinued or substituted, including antipsychotics (olanzapine, clozapine, quetiapine, etc.), valproate sodium, or lithium.
History of alcohol abuse within 1 year prior to screening, defined as daily consumption >3 standard drink units (men) or >2 standard drink units (women) sustained for >3 months (1 standard drink unit ≈ 10g pure alcohol).

Trial locations and contacts

1 site in 1 country. Contact the study team or a site near you to ask about taking part.

Jiajun Zhao, MD, PhD contact

0531-68776025

jjzhao@sdu.edu.cn

Xiude Fan, MD, PhD contact

+8613186067538

fanxiudexjtu@163.com

China1 site

Shandong Provincial Hospital Affiliated to Shandong First Medical University
Jinan, Shandong, 250021
Xiude Fan, MD, PhD, 13186067538, fanxiudexjtu@163.com
Jiajun Zhao, MD, PhD

Other trials in China

About this study

Official title: Efficacy and Safety of Mazdutide in Adults With Prediabetes: A Multicenter, Randomized, Double-Blind, Placebo-Controlled Clinical Trial (DREAM-PRE)

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.

Read the detailed description

BACKGROUND AND RATIONALE Prediabetes - encompassing impaired fasting glucose (IFG), impaired glucose tolerance (IGT), and elevated HbA1c (5.7-6.4%) - affects an estimated 352 million adults globally, with China bearing the highest absolute burden. Without intervention, approximately 5-10% of individuals with prediabetes progress to type 2 diabetes (T2D) annually. Reversal to Normal Glucose Regulation (NGR) is achievable but underexplored as a primary clinical endpoint.

Mazdutide (IBI362) is a GLP-1 receptor/glucagon receptor (GLP-1R/GCGR) dual agonist. Beyond GLP-1R-mediated glucose-dependent insulin secretion and appetite suppression, GCGR co-agonism enhances hepatic fatty acid oxidation and energy expenditure. This dual mechanism may address the overlapping pathophysiology of prediabetes - beta-cell dysfunction, insulin resistance, ectopic lipid accumulation, and excess adiposity - more comprehensively than GLP-1R monoagonists alone.

SCIENTIFIC RATIONALE FOR DOSE SELECTION Two maintenance doses are evaluated: 4 mg and 6 mg once weekly. Both doses demonstrated clinically meaningful HbA1c reduction and weight loss in prior trials (DREAMS-1, DREAMS-2) in patients with type 2 diabetes. The 4 mg dose represents a potentially efficacious and better-tolerated option, while the 6 mg dose achieves maximal receptor engagement. Comparing both doses against placebo in a prediabetes population allows dose-response characterization and informs optimal dosing for future prevention trials.

DISEASE MODIFICATION HYPOTHESIS The primary endpoint (NGR at Week 24) captures complete metabolic normalization across three glycemic domains simultaneously. Secondary assessment at Week 48 (24 weeks after treatment discontinuation) tests whether treatment induces durable disease modification - restoration of beta-cell function and insulin sensitivity - rather than pharmacological glucose suppression alone. The Disposition Index (product of insulin secretion and insulin sensitivity) serves as the key mechanistic secondary endpoint.

LIFESTYLE INTERVENTION BACKGROUND All participants receive standardized lifestyle intervention consistent with Chinese guidelines for prediabetes management, providing an active background that reflects real-world clinical practice and enhances external validity.

Conditions: Prediabetes, Impaired Fasting Glucose, Impaired Glucose Tolerance (Prediabetes)
Being tested: Mazdutide, Placebo, Standardized Lifestyle Intervention
Keywords: Mazdutide, IBI362, GLP-1R/GCGR dual agonist, Prediabetes, Diabetes prevention, Normal glucose regulation, Beta-cell function, Insulin resistance, Weight loss
Medical subject headings: Prediabetic State, Glucose Intolerance, Insulin Resistance, Weight Loss

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

MazdutideDrug
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.
PlaceboDrug
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.
Standardized Lifestyle InterventionBehavioural
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.

Study groups in NCT07654062
Study group	Role	What they receive
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. Receives: 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. Receives: 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. Receives: Drug: Placebo; Behavioral: Standardized Lifestyle Intervention

What is being measured

The primary outcome is the main question the study is designed to answer.

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).
Measured: Week 24

Secondary outcomes (29)

Change from Baseline in HbA1c
Measured: Week 24 and Week 48
Change from Baseline in Fasting Plasma Glucose
Measured: Week 24 and Week 48
Change from Baseline in OGTT 2-Hour Plasma Glucose
Measured: Week 24 and Week 48
IFG Remission Rate (FPG <6.1 mmol/L)
Measured: Week 24 and Week 48
IGT Remission Rate (OGTT 2h-PG <7.8 mmol/L)
Measured: Week 24 and Week 48
HbA1c Normalization Rate (HbA1c <5.7%)
Measured: Week 24 and Week 48
Proportion of Participants Maintaining Normal Glucose Regulation (NGR) at Week 48
Assessed 24 weeks after treatment discontinuation to evaluate durability of glycemic response.
Measured: Week 48
Cumulative Incidence of Progression to Type 2 Diabetes
Measured: Up to 48 weeks
Proportion of Week-24 NGR Responders Maintaining NGR at Week 48
Among participants who achieved NGR at Week 24, the proportion who simultaneously meet all three NGR criteria (HbA1c <5.7%, fasting plasma glucose <6.1 mmol/L, and OGTT 2-hour plasma glucose <7.8 mmol/L) at Week 48, assessed by central laboratory.
Measured: Week 48
Percent Change from Baseline in Body Weight
Measured: Week 24 and Week 48
Change from Baseline in Waist Circumference
Measured: Week 24 and Week 48
Proportion Achieving ≥5% Body Weight Reduction
Measured: Week 24 and Week 48
Proportion Achieving ≥10% Body Weight Reduction
Measured: Week 24 and Week 48
Change from Baseline in Disposition Index (DI)
Measured: Week 24 and Week 48
Change from Baseline in Insulinogenic Index (IGI30)
Measured: Week 24 and Week 48
Change from Baseline in Matsuda Insulin Sensitivity Index
Measured: Week 24 and Week 48
Change from Baseline in HOMA-IR
Measured: Week 24 and Week 48
Change from Baseline in HOMA-β
Measured: Week 24 and Week 48
Change from Baseline in OGTT Glucose AUC0-120
Measured: Week 24 and Week 48
Change from Baseline in OGTT Insulin AUC0-120
Measured: Week 24 and Week 48
Change from Baseline in Liver Fat Content by FibroScan CAP
Measured: Week 24 and Week 48
Fatty Liver Resolution Rate (CAP from ≥248 to <248 dB/m)
Measured: Week 24 and Week 48
Change from Baseline in ALT, AST, and GGT
Measured: Week 24 and Week 48
ALT Normalization Rate
Measured: Week 24 and Week 48
Change from Baseline in Fatty Liver Index (FLI)
Measured: Week 24 and Week 48
Change from Baseline in Lipid Panel (TG, TC, LDL-C, HDL-C, non-HDL-C)
Measured: Week 24 and Week 48
Change from Baseline in Systolic and Diastolic Blood Pressure
Measured: Week 24 and Week 48
Change from Baseline in Serum Uric Acid
Measured: Week 24 and Week 48
Change in Prevalence of Metabolic Syndrome
Measured: Week 24 and Week 48

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

Jul 2026Jul 2029

First posted17 Jun 2026
Study startJul 2026 (estimated)
Primary completionJun 2028 (estimated)
Study completionJul 2029 (estimated)

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Publications (9)Papers the sponsor has linked to this study.
Other trials for PrediabetesStudies of the same condition, open and under way.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 4
Primary purpose: Prevention
Allocation: Randomised
Intervention model: Parallel groups
Masking: Double blind
Who is masked: Participant, Investigator
Enrolment: 150 participants (estimated)

IDs, dates and publications

ClinicalTrials.gov ID: NCT07654062
Sponsor's protocol ID: DREAM-PRE-IIT-2026
Other IDs: SWYX:NO. 2026-1026
Acronym: DREAM-PRE
Status last verified: Jun 2026
First submitted: 4 Jun 2026
Last updated: 17 Jun 2026
Results posted: No
Data monitoring committee: Yes
FDA-regulated drug: No
FDA-regulated device: No
Individual data sharing: No: Individual participant data will not be shared publicly. This study is an investigator-initiated trial conducted in China. Participant data are subject to Chinese Personal Information Protection Law (PIPL) and cannot be transferred or disclosed to third parties without regulatory authorization. Aggregated summary data and statistical analysis code may be made available upon reasonable request to the corresponding author.

Publications

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.
PubMed 33567185
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.
PubMed 38907683
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.
PubMed 26132939
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.
PubMed 41407860
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.
PubMed 41407859
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.
PubMed 28655017
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.
PubMed 31036503
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.
PubMed 38092790
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.
PubMed 37943529

Interested in taking part?

Jiajun Zhao, MD, PhD

0531-68776025

jjzhao@sdu.edu.cn

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See sites and contacts

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Study at a glance

From the registry record, last updated by the sponsor on 17 Jun 2026. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: Efficacy and Safety of Mazdutide in Adults With Prediabetes: A Multicenter, Randomized, Double-Blind, Placebo-Controlled Clinical Trial (DREAM-PRE)
ClinicalTrials.gov ID: NCT07654062
Acronym / sponsor ID: DREAM-PRE / DREAM-PRE-IIT-2026
Conditions: Prediabetes, Impaired Fasting Glucose, Impaired Glucose Tolerance (Prediabetes)
Keywords: Mazdutide, IBI362, GLP-1R/GCGR dual agonist, Prediabetes, Diabetes prevention, Normal glucose regulation, Beta-cell function, Insulin resistance
Phase: Phase 4
Study type: Interventional
Recruitment status: Not yet recruiting
Enrolment: 150 participants (estimated)
Lead sponsor: Shandong Provincial HospitalOther government
Collaborators: Innovent Biologics, Inc.
Study start: Jul 2026 (estimated)
Primary completion: Jun 2028 (estimated)
Study completion: Jul 2029 (estimated)
First posted: 17 Jun 2026 (actual)
Results: Not posted in the source record

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Detailed description

Study design

Primary purpose: Prevention
Allocation: Randomised
Intervention model: Parallel groups
Masking: Double blind (participant, investigator)
Number of arms: 3

Arm	Type	Receives
Mazdutide 4 mg	Experimental	Drug: Mazdutide, Behavioral: Standardized Lifestyle InterventionMazdutide 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.
Mazdutide 6 mg	Experimental	Drug: Mazdutide, Behavioral: Standardized Lifestyle InterventionMazdutide 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.
Placebo	Placebo comparator	Drug: Placebo, Behavioral: Standardized Lifestyle InterventionMatching 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.

Who may qualify

Ages: 18 to 75 years
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (10 listed)

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:
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

Key exclusion criteria (22 listed)

Confirmed diabetes at screening (FPG ≥7.0 mmol/L, OGTT 2h-PG ≥11.1 mmol/L, or HbA1c ≥6.5%); or prior confirmed diagnosis of type 1 diabetes, type 2 diabetes, or other specific types of diabetes. Prior gestational diabetes in whom blood glucose has returned to prediabetes levels after delivery is NOT grounds for exclusion.
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).

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
MazdutideGLP-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.	Drug	Mazdutide 4 mg, Mazdutide 6 mg
PlaceboMatching 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.	Drug	Placebo
Standardized Lifestyle InterventionStructured 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.	Behavioural	Mazdutide 4 mg, Mazdutide 6 mg, Placebo

Primary outcome

Proportion of Participants Achieving Normal Glucose Regulation (NGR) at Week 24
Time frame: 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).

29 secondary outcomes

Change from Baseline in HbA1c
Time frame: Week 24 and Week 48
Change from Baseline in Fasting Plasma Glucose
Time frame: Week 24 and Week 48
Change from Baseline in OGTT 2-Hour Plasma Glucose
Time frame: Week 24 and Week 48
IFG Remission Rate (FPG <6.1 mmol/L)
Time frame: Week 24 and Week 48
IGT Remission Rate (OGTT 2h-PG <7.8 mmol/L)
Time frame: Week 24 and Week 48
HbA1c Normalization Rate (HbA1c <5.7%)
Time frame: Week 24 and Week 48
Proportion of Participants Maintaining Normal Glucose Regulation (NGR) at Week 48
Time frame: Week 48
Cumulative Incidence of Progression to Type 2 Diabetes
Time frame: Up to 48 weeks
Proportion of Week-24 NGR Responders Maintaining NGR at Week 48
Time frame: Week 48
Percent Change from Baseline in Body Weight
Time frame: Week 24 and Week 48
Change from Baseline in Waist Circumference
Time frame: Week 24 and Week 48
Proportion Achieving ≥5% Body Weight Reduction
Time frame: Week 24 and Week 48
Proportion Achieving ≥10% Body Weight Reduction
Time frame: Week 24 and Week 48
Change from Baseline in Disposition Index (DI)
Time frame: Week 24 and Week 48
Change from Baseline in Insulinogenic Index (IGI30)
Time frame: Week 24 and Week 48
Change from Baseline in Matsuda Insulin Sensitivity Index
Time frame: Week 24 and Week 48
Change from Baseline in HOMA-IR
Time frame: Week 24 and Week 48
Change from Baseline in HOMA-β
Time frame: Week 24 and Week 48
Change from Baseline in OGTT Glucose AUC0-120
Time frame: Week 24 and Week 48
Change from Baseline in OGTT Insulin AUC0-120
Time frame: Week 24 and Week 48
Change from Baseline in Liver Fat Content by FibroScan CAP
Time frame: Week 24 and Week 48
Fatty Liver Resolution Rate (CAP from ≥248 to <248 dB/m)
Time frame: Week 24 and Week 48
Change from Baseline in ALT, AST, and GGT
Time frame: Week 24 and Week 48
ALT Normalization Rate
Time frame: Week 24 and Week 48
Change from Baseline in Fatty Liver Index (FLI)
Time frame: Week 24 and Week 48
Change from Baseline in Lipid Panel (TG, TC, LDL-C, HDL-C, non-HDL-C)
Time frame: Week 24 and Week 48
Change from Baseline in Systolic and Diastolic Blood Pressure
Time frame: Week 24 and Week 48
Change from Baseline in Serum Uric Acid
Time frame: Week 24 and Week 48
Change in Prevalence of Metabolic Syndrome
Time frame: Week 24 and Week 48

Results and safety

This study is still under way. Results are not available in the source record yet.

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 17 Jun 2026.
Background: PubMed 33567185Wilding 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: PubMed 38907683Kahn 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: PubMed 26132939Pi-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: PubMed 41407860Guo 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: PubMed 41407859Zhu 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: PubMed 28655017Wang 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: PubMed 31036503Gong 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: PubMed 38092790Ji 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: PubMed 37943529Zhang 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.
Individual participant dataSharing planned: No. Individual participant data will not be shared publicly. This study is an investigator-initiated trial conducted in China. Participant data are subject to Chinese Personal Information Protection Law (PIPL) and cannot be transferred or disclosed to third parties without regulatory authorization. Aggregated summary data and statistical analysis code may be made available upon reasonable request to the corresponding author.

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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.

Jiajun Zhao, MD, PhD contact

0531-68776025

jjzhao@sdu.edu.cn

Xiude Fan, MD, PhD contact

+8613186067538

fanxiudexjtu@163.com

Jiajun Zhao, MD, PhD principal investigator

Shandong Provincial Hospital

1 site in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 4 study testing Mazdutide and Standardized Lifestyle Intervention in people with Prediabetes and Impaired Fasting Glucose, run by Shandong Provincial Hospital at 1 site in China.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 10 inclusion and 22 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: opening soon, as of the sponsor's last update on 17 Jun 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in China. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

Contact Jiajun Zhao, MD, PhD (0531-68776025, jjzhao@sdu.edu.cn), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Proportion of Participants Achieving Normal Glucose Regulation (NGR) at Week 24 (time frame: Week 24). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT07654062, which also lists 9 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 17 Jun 2026.