Prediabetes
Conditions
Keywords
Chiglitazar Sodium, PPAR agonist, Prediabetes, Impaired Glucose Tolerance, Impaired Fasting Glucose, Lifestyle Intervention
Brief summary
This multicenter, randomized, double-blind, placebo-controlled trial aims to evaluate the efficacy and safety of Chiglitazar Sodium combined with lifestyle intervention for reversing prediabetes to normal glucose metabolism. Eligible participants with prediabetes will be randomized 1:1 to receive either Chiglitazar Sodium 48 mg once daily or matching placebo, both combined with standardized lifestyle intervention, for 52 weeks, followed by a 12-week observation period and optional long-term extension. The primary endpoint is the reversion rate to normal glucose metabolism at week 64. Secondary endpoints include progression to type 2 diabetes, glycemic control, lipid profile, blood pressure, UACR, HOMA-IR, HOMA-β, body weight, BMI, and waist-to-height ratio. Exploratory endpoints include inflammatory markers and long-term cardiovascular outcomes. Safety endpoints include adverse events, vital signs, ECG, and laboratory parameters.
Detailed description
Prediabetes is an intermediate state of hyperglycemia that precedes the development of type 2 diabetes. Reversing prediabetes to normal glucose metabolism represents a promising strategy for diabetes prevention. Chiglitazar Sodium is a novel PPAR pan-agonist with potential benefits on glycemic control and metabolic parameters. This national multicenter study will be conducted across 30 sites in China. A total of 472 participants aged 18-70 years with prediabetes (according to Chinese expert consensus criteria, including IFG, IGT or IFG+IGT) and BMI 20-32 kg/m² will be enrolled. The study consists of four phases: Screening Period (up to 2 weeks): Assessment of eligibility including OGTT, laboratory tests, and medical history. Double-Blind Treatment Period (52 weeks): Eligible participants are randomized 1:1 to receive either Chiglitazar Sodium 48 mg once daily or matching placebo, both combined with standardized lifestyle intervention (diet and exercise according to Chinese Diabetes Prevention Guidelines). Study visits occur at weeks 4, 12, 24, 36, and 52. Observation Period (12 weeks, weeks 53-64): Participants who have not developed diabetes enter a 12-week drug-free observation period, with final assessment at week 64. Extension Period (up to week 156): Participants who have not developed diabetes and provide consent may continue follow-up for long-term cardiovascular outcomes assessment at weeks 104 and 156. The primary endpoint is the proportion of participants achieving reversion to normal glucose metabolism at week 64. Secondary endpoints include progression to type 2 diabetes, changes in fasting plasma glucose, OGTT (1h/2h PPG), HbA1c, lipid profile (TG, TC, LDL-C, HDL-C), blood pressure, UACR, HOMA-IR, HOMA-β, body weight, BMI, and waist-to-height ratio. Exploratory endpoints include changes in inflammatory markers (hsCRP, IL-6, TNF-α) and incidence of heart failure, non-fatal myocardial infarction, non-fatal stroke, cardiovascular death, or all-cause death through week 156. Safety will be monitored throughout.
Interventions
Chiglitazar Sodium tablet, 48 mg, oral, once daily, administered from randomization through week 52. Combined with standardized lifestyle intervention provided throughout the study period.
DRUGPlacebo
Matching placebo (Chiglitazar Sodium simulation tablet), 48 mg, oral, once daily, administered from randomization through week 52. Combined with standardized lifestyle intervention provided throughout the study period.
Sponsors
Second Xiangya Hospital of Central South University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 70 Years
Healthy volunteers
No
Inclusion criteria
1.Voluntarily signed informed consent. 2. Age 18 to 70 years, inclusive. 3. Diagnosed with prediabetes according to the Chinese expert consensus on intervention for adults with pre-diabetes (2023 edition), meeting any of the following criteria: 1. Impaired fasting glucose (IFG): fasting plasma glucose (FPG) ≥ 6.1 mmol/L and \< 7.0 mmol/L, with 2-hour postprandial glucose (2hPG) \< 7.8 mmol/L and HbA1c \< 6.5% 2. Impaired glucose tolerance (IGT): FPG \< 6.1 mmol/L, with 2hPG ≥ 7.8 mmol/L and \< 11.1 mmol/L, and HbA1c \< 6.5% 3. IFG + IGT, with HbA1c \< 6.5% 4. HbA1c 5.7% to 6.4% (inclusive), with FPG and OGTT 2hPG not meeting diabetes diagnostic criteria 4. Body Mass Index (BMI) 20-32 kg/m². 5. For women of childbearing potential, must agree to use a highly effective method of contraception throughout the study.
Exclusion criteria
1. Use of glucose-lowering medications within 3 months prior to screening. 2. Major cardiovascular or cerebrovascular events within 6 months prior to screening, defined as: 1)Acute myocardial infarction, coronary angioplasty or bypass surgery, valvular heart disease or valve repair, severe arrhythmias (e.g., ventricular fibrillation, atrial flutter, atrial fibrillation, etc.), unstable angina, transient ischemic attack, ischemic stroke, or hemorrhagic stroke 2)New York Heart Association (NYHA) class III or IV congestive heart failure 3)Current use of loop diuretics or digitalis 3.Uncontrolled hypertension: systolic blood pressure (SBP) ≥ 160 mmHg and/or diastolic blood pressure (DBP) ≥ 100 mmHg despite treatment, or use of three or more antihypertensive agents with inadequate control (SBP ≥ 160 mmHg or DBP ≥ 100 mmHg). 4.eGFR ≤ 15 mL/min/1.73 m² (CKD-EPI Creatinine Equation 2021). 5.Urinary albumin-to-creatinine ratio (UACR) \> 300 mg/g. 6.Hemoglobin \< 110 g/L. 7.Fasting triglycerides \> 5.6 mmol/L (500 mg/dL). 8.Active liver disease or significant hepatic dysfunction, defined as AST \> 2.5×ULN and/or ALT \> 2.5×ULN and/or total bilirubin \> 1.5×ULN. 9.Severe pulmonary disease with treatments that may potentially affect glucose metabolism (e.g., inhaled corticosteroids, beta-agonists). 10.History of acute or chronic pancreatitis, or history of gallbladder or bile duct disease (except post-cholecystectomy for gallstones or cholecystitis). 11.Gastrointestinal disorders affecting gastric emptying, such as gastroparesis, postoperative gastric stasis, idiopathic gastroparesis, gastroesophageal reflux disease, pyloric stenosis or obstruction, intestinal obstruction; severe chronic gastrointestinal disease (e.g., active ulcer, intestinal tuberculosis within 6 months prior to screening); history of frequent nausea, vomiting, or irregular gastrointestinal motility from any cause (e.g., habitual diarrhea, habitual constipation, inflammatory bowel disease, irritable bowel syndrome); or long-term use of medications directly affecting gastrointestinal motility. 12.Recent abdominal surgery or history of major abdominal surgery. 13.Thyroid dysfunction or other endocrine diseases affecting glucose metabolism (Cushing's syndrome, acromegaly, pheochromocytoma, prolactinoma, etc.), except stable treated hypothyroidism (for 3 months) or subclinical hypothyroidism not requiring treatment. 14.History of malignancy within 5 years prior to screening, or current malignancy. 15.History of tuberculosis or current use of anti-tuberculosis medications. 16.Current use of antipsychotic agents, alcohol abuse, or drug dependence. 17.Current use of thiazide diuretics, beta-blockers, nicotinic acid for lipid-lowering, systemic glucocorticoids, or weight-loss medications. 18.Known hypersensitivity to Chiglitazar Sodium or its components. 19.Pregnancy or breastfeeding. 20.Unexplained weight loss \> 10% of baseline body weight within 6 months prior to screening. 21.Participation in another clinical trial within 3 months prior to screening. 22.Any other condition that, in the investigator's judgment, would preclude the participant from completing the study or pose significant risk to the participant.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Reversion Rate to Normal Glucose Metabolism | Week 64 | Proportion of participants achieving reversion to normal glucose metabolism at week 64. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Reversion Rate to Normal Glucose Metabolism | Week 24, Week 52 | Proportion of participants achieving reversion to normal glucose metabolism at week 24 and week 52. |
| Progression Rate to Type 2 Diabetes | Week 24, Week 52, Week 64 | Proportion of participants progressing to type 2 diabetes at week 24, week 52, and week 64. |
| Change From Baseline in Fasting Plasma Glucose (FPG) | Week 24, Week 52, Week 64 | Change from baseline in fasting plasma glucose level. |
| Change From Baseline in OGTT 1-hour and 2-hour Postprandial Glucose (PPG) | Week 24, Week 52, Week 64 | Change from baseline in plasma glucose at 1 hour and 2 hours during oral glucose tolerance test. |
| Change From Baseline in HbA1c | Week 24, Week 52, Week 64 | Change from baseline in glycated hemoglobin level |
| Change From Baseline in Lipid Profile | Week 24, Week 52, Week 64 | Change from baseline in triglycerides (TG), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), and high-density lipoprotein cholesterol (HDL-C). |
| Change From Baseline in Blood Pressure | Week 24, Week 52, Week 64 | Change from baseline in systolic blood pressure (SBP) and diastolic blood pressure (DBP). |
| Change From Baseline in UACR | Week 24, Week 52, Week 64 | Change from baseline in urinary albumin-to-creatinine ratio |
| Change From Baseline in HOMA-IR | Week 24, Week 52, Week 64 | Change from baseline in Homeostatic Model Assessment of Insulin Resistance (HOMA-IR). |
| Change From Baseline in HOMA-β | Week 24, Week 52, Week 64 | Change from baseline in Homeostatic Model Assessment of β-cell function (HOMA-β). |
| Change From Baseline in Body Weight | Week 24, Week 52, Week 64 | Change from baseline in body weight |
| Change From Baseline in BMI | Week 24, Week 52, Week 64 | Change from baseline in body mass index (BMI). |
| Change From Baseline in Waist-to-Height Ratio | Week 24, Week 52, Week 64 | Change from baseline in waist-to-height ratio. |
Countries
China
Contacts
CONTACTZhiguang Zhou, MD, PhD
CONTACTChuqing Cao, MD, PhD
Outcome results
None listed