A Phase 4 interventional study of Mazdutide and Placebo in Prediabetes, Impaired Fasting Glucose and Impaired Glucose Tolerance (Prediabetes), sponsored by Shandong Provincial Hospital. Not yet recruiting at 1 site in China. Open to participants aged 18 Years to 75 Years. Per ClinicalTrials.gov, last updated 2026-06-17.
Sponsored by Shandong Provincial Hospital · Phase 4, Interventional, and Prevention
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.
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.
918 studies on the registry are indexed under Prediabetic State; 232 are open to participants now.
This study's planned enrollment of 150 is above the median of 62 across 762 interventional studies indexed under Prediabetic State.
Browse Prediabetic State studies →Shandong Provincial Hospital is the lead sponsor of 61 studies on the registry; 23 are open to participants now.
Counted across the registry records on this site, refreshed daily.
Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.
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
Exclusion Criteria:
arrhythmia on 12-lead at screening, including:
Mobitz Type II or third-degree atrioventricular block, sustained ventricular tachycardia (≥30 seconds or requiring cardioversion), >500 ms, or resting heart rate \<50 bpm (in subjects not using beta-blockers or calcium channel blockers).
Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
A blood test of average blood sugar over the past two to three months, given as a percentage or in mmol/mol. 6.5% (48 mmol/mol) or more is the usual threshold for diabetes, normally confirmed by a second test.
Weight in kilograms divided by height in metres squared. Example: 70 kg and 1.75 m gives 70 ÷ (1.75 × 1.75) ≈ 22.9.
What counts as overweight or obesity differs between countries (some use lower cut-offs), so go by the range the study states.
A drug or device being studied in a clinical trial.
It may be new, or already approved and being studied for another use, dose or form. Criteria often leave out people who took part in another study of one within a recent period, commonly 30 days or five half-lives.
The top of the normal range for a blood test, as set by the laboratory that runs it. Each lab prints its own range next to your result.
“≤ 2.5 × ULN” means the result can be up to two and a half times that top value.
A “mini-stroke”: temporary stroke-like symptoms caused by reduced blood flow to part of the brain, spinal cord or eye, without signs of a new stroke on a scan.
Stroke symptoms need emergency care at once, even if they go away.
The New York Heart Association’s four classes of how much heart failure limits physical activity.
Studies set their own limit — many outside heart failure leave out class III–IV, while heart failure studies may ask for a particular class. Check the class this study names.
Judged by the study doctor to matter for your health or for the study. It is a doctor’s decision, so ask the study team if you are unsure whether something counts.
A recording of the heart’s electrical activity, taken with stickers on the chest, arms and legs. It takes a few minutes and does not hurt.
On an ECG, the QT interval is the time the heart’s lower chambers take to activate electrically and recover in each beat. QTc is that time adjusted for heart rate (QTcF by Fridericia’s formula, QTcB by Bazett’s). Some medicines lengthen it, and a long QTc can raise the risk of a dangerous heart rhythm.
The study may name a correction formula and a limit in milliseconds, often around 450–480.
Two enzymes measured in a routine blood test of the liver. Higher levels can mean the liver is under strain or damaged. SGPT and SGOT are older names for ALT and AST.
Criteria usually give a limit as a multiple of the upper limit of normal (ULN), often higher when cancer has spread to the liver.
A yellow substance made when red blood cells are broken down, which the liver clears. A high level can mean a problem with the liver or the bile ducts.
Criteria often allow more for people with Gilbert’s syndrome, a harmless inherited condition that raises bilirubin.
GFR (glomerular filtration rate) is how much blood the kidneys filter each minute. It is usually estimated from a blood test — eGFR, by formulas such as CKD-EPI or MDRD — and some studies ask for it to be measured directly instead. Usually given in mL/min/1.73 m².
Check the method, the units and the minimum the study states. A value of 90 or above is in the normal-or-high range, but kidney damage can show in other tests too.
Malignancy means cancer. Criteria about another or earlier malignancy ask whether you have had a different cancer, usually within a set number of years.
Some are commonly allowed, such as treated skin cancers other than melanoma and early cancers removed completely — check the exceptions this study lists.
The other ingredients in a medicine besides the active drug, such as fillers, colours or preservatives.
Anti-inflammatory medicines such as prednisone, prednisolone and dexamethasone — not the anabolic steroids used for muscle.
Studies differ in what they allow: check which steroid medicines, routes (tablets, injections, creams, inhalers, eye drops) and doses this study accepts.
Informed consent
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
HbA1c
A blood test of average blood sugar over the past two to three months, given as a percentage or in mmol/mol. 6.5% (48 mmol/mol) or more is the usual threshold for diabetes, normally confirmed by a second test.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
BMI (body mass index)
Weight in kilograms divided by height in metres squared. Example: 70 kg and 1.75 m gives 70 ÷ (1.75 × 1.75) ≈ 22.9.
What counts as overweight or obesity differs between countries (some use lower cut-offs), so go by the range the study states.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Investigational drug or device
A drug or device being studied in a clinical trial.
It may be new, or already approved and being studied for another use, dose or form. Criteria often leave out people who took part in another study of one within a recent period, commonly 30 days or five half-lives.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
ULN (upper limit of normal)
The top of the normal range for a blood test, as set by the laboratory that runs it. Each lab prints its own range next to your result.
“≤ 2.5 × ULN” means the result can be up to two and a half times that top value.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
TIA (transient ischaemic attack)
A “mini-stroke”: temporary stroke-like symptoms caused by reduced blood flow to part of the brain, spinal cord or eye, without signs of a new stroke on a scan.
Stroke symptoms need emergency care at once, even if they go away.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
NYHA class (heart failure)
The New York Heart Association’s four classes of how much heart failure limits physical activity.
Studies set their own limit — many outside heart failure leave out class III–IV, while heart failure studies may ask for a particular class. Check the class this study names.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Clinically significant
Judged by the study doctor to matter for your health or for the study. It is a doctor’s decision, so ask the study team if you are unsure whether something counts.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
ECG (electrocardiogram)
A recording of the heart’s electrical activity, taken with stickers on the chest, arms and legs. It takes a few minutes and does not hurt.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
QT and QTc
On an ECG, the QT interval is the time the heart’s lower chambers take to activate electrically and recover in each beat. QTc is that time adjusted for heart rate (QTcF by Fridericia’s formula, QTcB by Bazett’s). Some medicines lengthen it, and a long QTc can raise the risk of a dangerous heart rhythm.
The study may name a correction formula and a limit in milliseconds, often around 450–480.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
ALT and AST (liver enzymes)
Two enzymes measured in a routine blood test of the liver. Higher levels can mean the liver is under strain or damaged. SGPT and SGOT are older names for ALT and AST.
Criteria usually give a limit as a multiple of the upper limit of normal (ULN), often higher when cancer has spread to the liver.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Bilirubin
A yellow substance made when red blood cells are broken down, which the liver clears. A high level can mean a problem with the liver or the bile ducts.
Criteria often allow more for people with Gilbert’s syndrome, a harmless inherited condition that raises bilirubin.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
GFR and eGFR (kidney filtering)
GFR (glomerular filtration rate) is how much blood the kidneys filter each minute. It is usually estimated from a blood test — eGFR, by formulas such as CKD-EPI or MDRD — and some studies ask for it to be measured directly instead. Usually given in mL/min/1.73 m².
Check the method, the units and the minimum the study states. A value of 90 or above is in the normal-or-high range, but kidney damage can show in other tests too.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Cancer (malignancy)
Malignancy means cancer. Criteria about another or earlier malignancy ask whether you have had a different cancer, usually within a set number of years.
Some are commonly allowed, such as treated skin cancers other than melanoma and early cancers removed completely — check the exceptions this study lists.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Excipients
The other ingredients in a medicine besides the active drug, such as fillers, colours or preservatives.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Corticosteroids (steroids)
Anti-inflammatory medicines such as prednisone, prednisolone and dexamethasone — not the anabolic steroids used for muscle.
Studies differ in what they allow: check which steroid medicines, routes (tablets, injections, creams, inhalers, eye drops) and doses this study accepts.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
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 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
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
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.
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.
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.
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 24
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
Assessed 24 weeks after treatment discontinuation to evaluate durability of glycemic response.
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
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.
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
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 48
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 48
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 48
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 48
Proportion of Participants Maintaining NGR at Week 72 and Week 96
Time frame: Week 72 and Week 96
Long-term Changes in Glycemic Parameters, Body Weight, Liver Fat Content, Disposition Index, and Cumulative Incidence of T2D from Baseline to Week 96
In participants completing extended long-term follow-up, the following outcomes are assessed at Week 72 and Week 96: 1. Cumulative incidence of progression to type 2 diabetes (FPG ≥7.0 mmol/L, OGTT 2h-PG ≥11.1 mmol/L, or HbA1c ≥6.5%, confirmed by central laboratory); 2. Change from baseline in HbA1c (%); 3. Change from baseline in fasting plasma glucose (mmol/L); 4. Change from baseline in OGTT 2-hour plasma glucose (mmol/L); 5. Percent change from baseline in body weight (kg); 6. Change from baseline in liver fat content by FibroScan CAP (dB/m); 7. Change from baseline in Disposition Index (product of Insulinogenic Index IGI30 and Matsuda Insulin Sensitivity Index). Continuous outcomes assessed by MMRM; categorical outcomes by NRI. Results reported per treatment arm with 95% CI.
Time frame: Week 72 and Week 96
Plan to share: 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.
Start is estimated for Jul 2026; primary completion for Jun 2028, 23 months later.
Of 30 phase 4 interventional studies under Prediabetic State, half reached primary completion within 40 months of starting (the median), counting those still running; a quarter within 20 and three quarters within 47. This study's planned 23 months is below that.
How these figures are worked out, and which studies are left out of them.
This study is not yet recruiting, as verified in Jun 2026. You cannot join it, but the record below documents what was studied.
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Studies of the drug tested here: Mazdutide
Shandong Provincial Hospital