Evaluation of Chiglitazar Sodium With Lifestyle Intervention for Reversing Prediabetes

Prediabetes Reversion Through Combined Intervention and Strict Evaluation Trial: A Multicenter, Double-Blind, Randomized, Placebo-Controlled Study on the Efficacy of Chiglitazar Sodium Combined With Lifestyle Intervention in Restoring Normal Glucose Tolerance in Prediabetic Patients

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.

Study Overview

• Status: Not yet recruiting
• Conditions: Prediabetes
• Intervention / Treatment: Drug: Chiglitazar sodium; Drug: Placebo

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.

• Study Type: Interventional
• Enrollment (Estimated): 472
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Zhiguang Zhou, MD, PhD; Phone Number: +8673185292154; Email: zhouzhiguang@csu.edu.cn
• Study Contact Backup: Name: Chuqing Cao, MD, PhD; Phone Number: +8673185292154; Email: caochuqing@csu.edu.cn

Study Locations

• China
  • Beijing, China
    • Xuanwu Hospital Capital Medical University
    • Contact: Yu Sun, MD, PhD; Phone Number: +861083198384; Email: 18560083995@163.com
    • Principal Investigator: YU Sun, MD, PhD
  • Beijing, China
    • Beijing Tsinghua Changgung Hospital
    • Contact: Jianzhong Xiao; Phone Number: +861056118567; Email: xjza01150@btch.edu.cn
  • Beijing, China
    • Emergency General Hospital
    • Contact: Kailiang Wang, MD, M.M.; Phone Number: +861087935595; Email: ht15s@163.com
  • Chongqing, China, 400038
    • The Southwest Hospital of the Army Medical University
    • Contact: Min Long, MD, PhD; Phone Number: +862365318301; Email: chzijing@126.com
    • Principal Investigator: Min Long, MD, PhD
  • Shanghai, China
    • Shanghai Ninth People's Hospital
    • Contact: Jie Qiao, MD, PhD; Phone Number: +862123271699; Email: qiaoj2001@126.com
  • Shanghai, China
    • Tongji Hospital of Tongji University
  • Shenzhen, China
    • Shenzhen Bao'an People's Hospital
    • Contact: Jisu Xue, MD, PhD; Phone Number: +8675527783061; Email: baxjs@126.com
  • Shenzhen, China
    • Shenzhen Bao'an Traditional Chinese Medicine Hospital
    • Contact: Yanping Zheng, MD, M.M.; Phone Number: +8675527831439; Email: panyanyes@163.com
  • Fujian
    • Quanzhou, Fujian, China
      • Quanzhou First Hospital, Fujian
      • Contact: Yi Zhang, MD, PhD; Phone Number: +8659522277157; Email: 2005064@163.com
  • Guangdong
    • Guangzhou, Guangdong, China
      • The First Affiliated Hospital of Guangzhou Medical University
      • Contact: Xiaoyan Chen, MD, PhD; Phone Number: +862083062114; Email: gzscxy@126.com
  • Heilongjiang
    • Harbin, Heilongjiang, China, 150086
      • The Second Affiliated Hospital of Harbin Medical University
      • Contact: Hong Qiao, MD, PhD; Phone Number: +8645186605084; Email: 13359864888@163.com
      • Principal Investigator: Hong Qiao, MD, PhD
    • Harbin, Heilongjiang, China, 150010
      • The First Hospital of Harbin
      • Contact: Binhua Xu, MD, M.M.; Phone Number: +8645184883051; Email: binhuaxu@sina.com
      • Principal Investigator: Binhua Xu, MD, M.M.
  • Henan
    • Luoyang, Henan, China
      • The First Affiliated Hospital of Henan University of Science & Technology
      • Contact: Hongwei Jiang, MD, PhD; Phone Number: +8637964922216; Email: jianghw@haust.edu.cn
  • Hubei
    • Wuhan, Hubei, China, 430071
      • Zhongnan Hospital of Wuhan University
      • Contact: Zhe Dai, MD, PhD; Phone Number: +862767812787; Email: betamm@163.com
      • Principal Investigator: Zhe Dai, MD, PhD
  • Hunan
    • Changde, Hunan, China
      • The First People's Hospital of Changde City
      • Contact: Shenglian Gan, MD, M.M.; Phone Number: +867367788890; Email: Gslghy03@sina.com
    • Changsha, Hunan, China
      • The Third Xiangya Hospital of Central South University
      • Contact: Ping Jin, MD, M.M.; Phone Number: +8673188618938; Email: ping.jin06@csu.edu.cn
    • Changsha, Hunan, China
      • People's Hospital of Hunan Province
      • Contact: Xinlan Zhao, MD, M.M.; Phone Number: +8673183929085; Email: qiqihaohao@163.com
    • Changsha, Hunan, China, 410011
      • The Second Xiangya Hospital, Central South University
      • Principal Investigator: Zhiguang Zhou, MD, PhD
      • Contact: Chuqing Cao, MD, PhD; Phone Number: +8673185292154; Email: caochuqing@csu.edu.cn
      • Sub-Investigator: Chuqing Cao, MD, PhD
    • Changsha, Hunan, China
      • Changsha Eighth Hospital
      • Contact: Weidong Zhou, MD, PhD; Phone Number: +8673185259000; Email: zhousufe@outlook.com
    • Loudi, Hunan, China
      • Loudi Central Hospital
      • Contact: Weiping Sun, MD, PhD; Phone Number: +867388527739; Email: sunwp07@163.com
    • Xiangtan, Hunan, China
      • The Central Hospital of Xiangtan
      • Contact: Wei Cheng, MD, M.M.; Phone Number: +8673158214922; Email: powerchengwei@163.com
    • Yongzhou, Hunan, China
      • The Central Hospital of Yongzhou
      • Contact: Wei Liu, MD, M.M.; Phone Number: +867468859487; Email: 786851038@outlook.com
    • Yueyang, Hunan, China
      • Yueyang People's Hospital
      • Contact: Dijun Zhou, MD, PhD; Phone Number: +867308725393; Email: Z121300@126.com
  • Jiangsu
    • Nanjing, Jiangsu, China
      • Sir Run Run Hospital, Nanjing Medical University
      • Contact: Yu Liu; Phone Number: +862587115593; Email: hhm0403@163.com
  • Shanxi
    • Changzhi, Shanxi, China
      • Heji Hospital Affiliated to Changzhi Medical College
      • Contact: Xiaohong Niu, MD, PhD; Phone Number: +863553552855; Email: 610115220@qq.com
  • Sichuan
    • Chengdu, Sichuan, China, 610072
      • Sichuan Academy of Medical Sciences & Sichuan Provincial People's Hospital
      • Contact: Limin Tian, MD,PhD; Phone Number: +862887393449; Email: 1072027801@qq.com
      • Principal Investigator: Limin Tian, MD,PhD
    • Chengdu, Sichuan, China, 610036
      • The Third People's Hospital of Chengdu
      • Contact: Xiaowei Zhong, MD,PhD; Phone Number: +862861318530; Email: 13541044788@126.com
      • Principal Investigator: Xiaowei Zhong, MD,PhD
    • Chengdu, Sichuan, China, 610499
      • Chengdu First People's Hospital
      • Contact: Lin Pu, MD,M.M.; Phone Number: +862885313280; Email: 541371995@qq.com
      • Principal Investigator: Lin Pu, MD,M.M.
  • Yunnan
    • Kunming, Yunnan, China
      • The First Affiliated Hospital of Kunming Medical University
      • Contact: Yushan Xu, MD, PhD; Phone Number: +8687165324888; Email: xuyushan1019@126.com
  • Zhejiang
    • Hangzhou, Zhejiang, China
      • The Second Affiliated Hospital Zhejiang University School of Medicine
      • Contact: Chao Zheng, MD, PhD; Phone Number: +8657187783759; Email: chao_zheng@zju.edu.cn

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Chiglitazar Sodium + Lifestyle Intervention; Participants will receive Chiglitazar Sodium 48 mg orally once daily, combined with standardized lifestyle intervention (diet and exercise counseling), for 52 weeks.	Drug: Chiglitazar sodium; Chiglitazar Sodium tablet, 48 mg, oral, once daily, administered from randomization through week 52. Combined with standardized lifestyle intervention provided throughout the study period.
Placebo Comparator: Placebo + Lifestyle Intervention; Participants will receive matching placebo (Chiglitazar Sodium simulation tablet) 48 mg orally once daily, combined with standardized lifestyle intervention (diet and exercise counseling), for 52 weeks.	Drug: Placebo; 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Reversion Rate to Normal Glucose Metabolism	Proportion of participants achieving reversion to normal glucose metabolism at week 64.	Week 64

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Reversion Rate to Normal Glucose Metabolism	Proportion of participants achieving reversion to normal glucose metabolism at week 24 and week 52.	Week 24, Week 52
Progression Rate to Type 2 Diabetes	Proportion of participants progressing to type 2 diabetes at week 24, week 52, and week 64.	Week 24, Week 52, Week 64
Change From Baseline in Fasting Plasma Glucose (FPG)	Change from baseline in fasting plasma glucose level.	Week 24, Week 52, Week 64
Change From Baseline in OGTT 1-hour and 2-hour Postprandial Glucose (PPG)	Change from baseline in plasma glucose at 1 hour and 2 hours during oral glucose tolerance test.	Week 24, Week 52, Week 64
Change From Baseline in HbA1c	Change from baseline in glycated hemoglobin level	Week 24, Week 52, Week 64
Change From Baseline in Lipid Profile	Change from baseline in triglycerides (TG), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), and high-density lipoprotein cholesterol (HDL-C).	Week 24, Week 52, Week 64
Change From Baseline in Blood Pressure	Change from baseline in systolic blood pressure (SBP) and diastolic blood pressure (DBP).	Week 24, Week 52, Week 64
Change From Baseline in UACR	Change from baseline in urinary albumin-to-creatinine ratio	Week 24, Week 52, Week 64
Change From Baseline in HOMA-IR	Change from baseline in Homeostatic Model Assessment of Insulin Resistance (HOMA-IR).	Week 24, Week 52, Week 64
Change From Baseline in HOMA-β	Change from baseline in Homeostatic Model Assessment of β-cell function (HOMA-β).	Week 24, Week 52, Week 64
Change From Baseline in Body Weight	Change from baseline in body weight	Week 24, Week 52, Week 64
Change From Baseline in BMI	Change from baseline in body mass index (BMI).	Week 24, Week 52, Week 64
Change From Baseline in Waist-to-Height Ratio	Change from baseline in waist-to-height ratio.	Week 24, Week 52, Week 64

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline in Inflammatory Markers	Change from baseline in high-sensitivity C-reactive protein (hsCRP), interleukin-6 (IL-6), and tumor necrosis factor-alpha (TNF-α).	Week 24, Week 52, Week 64
Incidence of Composite Cardiovascular Event	Incidence of non-fatal myocardial infarction, non-fatal stroke, cardiovascular death, or heart failure throughout.	Week 104, Week 156
Incidence of All-Cause Death	Incidence of all-cause death throughout.	Week 104, Week 156
Incidence of Adverse Events (AEs) and Serious Adverse Events (SAEs)	Overall incidence of treatment-emergent adverse events and serious adverse events throughout the study.	Throughout the study (up to week 156)

Collaborators and Investigators

• Sponsor: Second Xiangya Hospital of Central South University

Study record dates

Study Major Dates

• Study Start (Estimated): April 18, 2026
• Primary Completion (Estimated): December 31, 2028
• Study Completion (Estimated): December 31, 2029

Study Registration Dates

• First Submitted: April 22, 2026
• First Submitted That Met QC Criteria: April 22, 2026
• First Posted (Actual): April 30, 2026

Study Record Updates

• Last Update Posted (Actual): April 30, 2026
• Last Update Submitted That Met QC Criteria: April 22, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Keywords: Prediabetes; Impaired Fasting Glucose; Lifestyle Intervention; Impaired Glucose Tolerance; PPAR agonist; Chiglitazar Sodium
• Additional Relevant MeSH Terms: Endocrine System Diseases; Metabolic Diseases; Glucose Metabolism Disorders; Diabetes Mellitus; Hyperglycemia; Nutritional and Metabolic Diseases; Prediabetic State; Glucose Intolerance
• Other Study ID Numbers: PRECISE trial

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No