Mazdutide for Adults With Prediabetes: A Randomized, Double-Blind, Placebo-Controlled Trial (DREAM-PRE)
Trial statusNot yet recruiting
Trial phasePhase 4
Trial typeInterventional
Biological sexAll
Age18-75
SponsorShandong Provincial Hospital
About this trial
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.
Eligibility criteria
This trial does not accept healthy volunteersQualifiers
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
Impaired Glucose Tolerance (IGT): 75g OGTT 2-hour plasma glucose
7.8 mmol/L and <11.1 mmol/L
Disqualifiers
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.
Trial design
Design model
Parallel
Treatments tested in this trial
Mazdutide
DrugGLP-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.
Placebo
DrugMatching 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 Intervention
BehavioralStructured 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.
Treatment groups
150 Participants
are divided into 3 treatment groupsGroup A: Mazdutide 4 mgExperimental treatment 2 interventions
Group B: Mazdutide 6 mgExperimental treatment 2 interventions
Group C: PlaceboPlacebo comparator 2 interventions
Trial outcomes
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).
Time frame
Week 24Secondary outcomes
1
Change from Baseline in HbA1c
Time frame
Week 24 and Week 482
Change from Baseline in Fasting Plasma Glucose
Time frame
Week 24 and Week 483
Change from Baseline in OGTT 2-Hour Plasma Glucose
Time frame
Week 24 and Week 484
IFG Remission Rate (FPG <6.1 mmol/L)
Time frame
Week 24 and Week 48Other outcomes
1
Difference in Proportion of Participants Achieving NGR Between Mazdutide 6 mg and 4 mg Arms at Week 24
Post-hoc head-to-head comparison of NGR rates between the mazdutide 6 mg and 4 mg arms at Week 24 and Week 48, assessed by CMH test; reported as risk difference (percentage points) with 95% CI. A monotonic dose-response trend across the three ordered treatment groups (placebo, mazdutide 4 mg, mazdutide 6 mg) is also assessed using the Cochran-Armitage trend test; reported as trend test p-value and NGR proportion per arm.
Time frame
Week 24 and Week 482
NGR Rate at Week 24 by Baseline Prediabetes Type (IFG Only, IGT Only, IFG+IGT, or Elevated HbA1c Only)
Proportion of participants achieving NGR at Week 24 in pre-specified subgroups defined by baseline prediabetes type: (1) IFG only (FPG ≥6.1 and \<7.0 mmol/L with OGTT 2h-PG \<7.8 mmol/L); (2) IGT only (OGTT 2h-PG ≥7.8 and \<11.1 mmol/L with FPG \<6.1 mmol/L); (3) IFG+IGT combined (both criteria simultaneously met); (4) elevated HbA1c only (HbA1c 5.7-6.4% with FPG \<6.1 mmol/L and OGTT 2h-PG \<7.8 mmol/L). Treatment effect estimated within each subgroup with interaction p-value reported.
Time frame
Week 24 and Week 483
NGR Rate at Week 24 by Baseline BMI Subgroup (<28 vs ≥28 kg/m²)
Proportion of participants achieving NGR at Week 24 in pre-specified subgroups defined by baseline BMI (\<28 vs ≥28 kg/m²). Treatment effect estimated within each subgroup with interaction p-value reported.
Time frame
Week 24 and Week 484
Change from Baseline in Serum Proteomics and Metabolomics
Exploratory analysis of changes from baseline in serum proteomics and metabolomics at Week 24 and Week 48. Reported as number of significantly altered proteins/metabolites and enriched biological pathways.
Time frame
Week 24 and Week 48Sponsors and contacts
Click on the lead sponsor to view all of their trials.
Shandong Provincial Hospital
Lead sponsor
Innovent Biologics, Inc.
Collaborator
Source ClinicalTrials.gov
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