Henagliflozin's Impact on Prediabetes Remission
- Conditions
- Type 2 DiabetesGlucose Metabolism DisordersPrediabetic StatePreDiabetes
- Interventions
- Registration Number
- NCT06448130
- Lead Sponsor
- Shandong Provincial Hospital
- Brief Summary
This clinical trial evaluates the effectiveness of Henagliflozin combined with lifestyle interventions for managing patients with prediabetes. As global prediabetes rates rise, increasing the risk of diabetes and vascular issues, addressing treatment gaps is essential. Henagliflozin, a novel SGLT2 inhibitor developed in China, aims to improve glucose control and metabolic health when paired with lifestyle changes.
The study's primary objectives include: assessing whether Henagliflozin can achieve normoglycemia in prediabetic patients after 6 months of treatment.
The trial will compare three groups (Henagliflozin 5mg, 10mg, and a placebo), focusing on efficacy and safety. Participants, assigned randomly, will undergo a 6-month treatment phase and an 18-month follow-up. Regular health assessments will monitor glucose levels, metabolic health, and risks of major complications like cardiovascular events and microvascular diseases, with additional evaluations of C-peptide and insulin changes.
Structured as a multicenter, randomized, double-blind, placebo-controlled study, it involves 984 prediabetic adults across 50 medical institutions in China. This comprehensive approach could redefine prediabetes management by integrating drug therapy with lifestyle modifications.
- Detailed Description
This research is launched in light of the global surge in prediabetes, a condition that markedly increases the risk of developing type 2 diabetes and related vascular complications. While lifestyle modifications are the frontline defense against prediabetes, the variability in individual responses often requires the integration of pharmacological treatments. Studies have shown that drugs such as metformin, acarbose, SGLT2 inhibitors, GLP-1 agonists, GIP/GLP-1 receptor agonists, thiazolidinediones, and orlistat effectively curb the progression to diabetes. Yet, there remains a gap in specific research addressing the intervention needs of the prediabetic population in China.
Currently, acarbose is the only drug approved in the Chinese market for treating patients with impaired glucose tolerance, highlighting a limited range of therapeutic options for prediabetes. SGLT2 inhibitors, as a newer class of hypoglycemic agents, have demonstrated significant promise in reducing major cardiovascular events in high-risk patients with type 2 diabetes, enhancing outcomes in heart failure, and providing renal protection. However, there is a scarcity of large-scale, prospective studies on the impact of SGLT2 inhibitors in prediabetes. Henagliflozin, the first original SGLT2 inhibitor developed in China and launched on December 31, 2021, is being studied to assess its effectiveness combined with lifestyle interventions in the prediabetic demographic, aiming to fill a crucial void in the current treatment paradigm.
This study aims to assess the combined benefits of Henagliflozin and lifestyle modifications in managing prediabetes. The investigators conducted a two-year prospective, randomized, double-blind, placebo-controlled trial across 50 medical institutions in various provinces of China. It is planned to enroll 984 adult prediabetic patients who had not previously been treated with antidiabetic medications. Participants meeting inclusion criteria were randomly assigned to one of three groups: Henagliflozin 5mg, Henagliflozin 10mg, or placebo. The intensive intervention phase, consisting of pharmacotherapy combined with lifestyle changes, lasted for 6 months, followed by an 18-month follow-up period focusing solely on lifestyle interventions.
The primary endpoint is the proportion of participants achieving normoglycemia after 6 months of intervention, with subsequent assessments at 12 months. Secondary endpoints include short-term (0-12 months) and long-term (12-24 months) changes in glucose control, metabolic indicators such as body weight, body mass index (BMI), body fat content, waist and hip circumference, lipid profiles, blood pressure, serum uric acid levels, hepatic steatosis, and carotid intima-media thickness. Exploratory outcomes encompass changes in C-peptide and insulin levels from baseline to 6 months, and the risk of major adverse cardiovascular events (MACE) from baseline to 24 months and beyond.
Recruitment & Eligibility
- Status
- NOT_YET_RECRUITING
- Sex
- All
- Target Recruitment
- 984
- Male or female subjects between the ages of 18 and 65 years;
- Individuals without hypoglycemic therapy before, including hypoglycemic drugs or traditional Chinese medicine formulations with hypoglycemic effects;
- Prediabetic patients as defined by Expert Consensus on Intervention for Prediabetes in Chinese Adults, 2023 Edition:1)Fasting plasma glucose (FPG) between 6.1 and 7.0 mmol/L and/or 2-hour postprandial glucose (2h-PPG) between 7.8 and 11.1 mmol/L; 2)And/or HbA1c between 5.7% and 6.5%;
- Individuals willing to provide written informed consent and can comply with study procedures and follow-up.
- Allergic to Henagliflozin;
- Previously diagnosed with diabetes;
- HbA1c ≥ 6.5% or FPG ≥ 7.0 mmol/L or PPG ≥ 11.1 mmol/L;
- Use of GLP-1 receptor agonists, orlistat, or other weight-reducing drugs in the past 3 months;
- Fluctuation in weight by 5% or more in the past month;
- Use of drugs affecting glucose synthesis, absorption, or metabolism, such as glucocorticoids (e.g., prednisone, dexamethasone), contraceptives, growth hormone, hormonal replacement therapy (estrogen and progesterone), immunosuppressants (e.g., cyclosporine A, tacrolimus), anti-tuberculosis drugs (e.g., isoniazid, rifampicin);
- Untreated hyperthyroidism or hypothyroidism, excluding those with normal thyroid function after treatment;
- Persistently uncontrolled hypertension (used antihypertensive drugs but was not effectively controlled in the 3 months prior to enrollment) or currently use 3 or more antihypertensive drugs (including diuretics);
- Assessed by the investigator to be at high risk of genitourinary system infections, such as history of recurrent urinary tract infections or reproductive system infections, long-term placement of urinary catheters, or history of urological surgery;
- Other obesity caused by endocrine disorders, such as Cushing's syndrome;
- Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) levels > 3 times of the upper limit of the normal range (UNL);
- eGFR less than 30 mL/min/1.73 m2, severe kidney damage, end-stage renal disease or requiring dialysis;
- Significant cardiovascular diseases including myocardial infarction, congestive heart failure (≥grade III New York Heart Association), left ventricular ejection fraction≤40%, or cerebrovascular accidents;
- Impaired consciousness and various mental health disorders;
- Malignant tumors and other serious illnesses;
- Pregnant or breast-feeding or planning pregnancy within 24 months;
- Enrolled in another clinical trial currently or within the 3 months prior to enrollment;
- Identified by the investigator that lacks sufficient motivation to continue the long-term clinical trial (e.g., out-of-town study, work plan, need to care for family members), or considered prefer to withdraw from the trial for non-medical reasons (such as social issues).
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description placebo+ lifestyle intervention Placebo placebo 10mg + placebo 5mg po qd + lifestyle intervention for 6 months Henagliflozin5mg + lifestyle intervention Henagliflozin 5mg Henagliflozin 5mg+ placebo 10mg po qd + lifestyle intervention for 6 months Henagliflozin10mg+ lifestyle intervention Henagliflozin 10mg Henagliflozin 10mg+ placebo 5mg po qd + lifestyle intervention for 6 months
- Primary Outcome Measures
Name Time Method Normoglycemia Achievement Rates Post-6-Month Intervention From 6 months post-intervention to 12 months This measure assesses the proportion of participants who achieve normoglycemia from the end of a 6-month intervention until the 12-month assessment point. Normoglycemia is defined as fasting plasma glucose (FPG) less than 6.1 mmol/L and 2-hour post-prandial glucose (2h-PPG) less than 7.8 mmol/L. The measure includes rates of sustained remission (normal glycemic status lasting more than 6 months post-medication cessation), partial remission (lasting 3-6 months), and temporary remission (lasting less than 3 months).
- Secondary Outcome Measures
Name Time Method Incidence of New-Onset Type 2 Diabetes From 0 to 24 months Incidence of new-onset type 2 diabetes within 24 months in the three study groups.
Blood Glucose Control Normalization From 6 months post-intervention to 24 months Proportion and duration of normalization of blood glucose levels within 24 months in the three study groups.
Changes in HbA1c Levels From 0 to 24 months Changes in HbA1c levels over the 24-month period in the three study groups.
Changes in serum uric acid levels over 24 Months From 0 to 24 months Changes in serum uric acid levels in the three study groups over 24 Months.
Changes in Body Mass Index (BMI) over 24 Months From 0 to 24 months Calculation of BMI in kg/m² using the formula: weight (kg) / (height (m)²), measured at multiple time points within the 24-month period.
Risk of Renal diseases From 0 to 24 months Risk of renal diseases (e.g., diabetic nephropathy/chronic kidney disease) in the three study groups over 0-24 months.
Changes in hepatic steatosis over 24 Months From 0 to 24 months Changes in hepatic steatosis assessed by abdominal ultrasound in the three study groups over 24 Months.
Impact of Glycemic Status at 12 Months From 12 months to 24 months Impact of glycemic status at 12 months on subsequent reversal to normoglycemia and risk of new-onset type 2 diabetes during the 12-24 month follow-up period in the three study groups.
Changes in blood pressure over 24 Months From 0 to 24 months Changes in systolic and diastolic blood pressure in the three study groups over 24 Months.
Changes in carotid intima-media thickness over 24 Months From 0 to 24 months Changes in carotid intima-media thickness measured by carotid ultrasound in the three study groups over 24 Months.
Changes in Total Cholesterol (TC) over 24 Months From 0 to 24 months Measurement of Total Cholesterol (TC) levels in millimoles per liter (mmol/L) using standardized laboratory procedures. Fasting blood samples will be collected at multiple time points within the 24-month period to assess changes over time.
Changes in Triglycerides (TG) over 24 Months From 0 to 24 months Measurement of Triglycerides (TG) levels in millimoles per liter (mmol/L) using standardized laboratory procedures. Fasting blood samples will be collected at multiple time points within the 24-month period to assess changes over time.
Changes in Low-Density Lipoprotein Cholesterol (LDL-c) over 24 Month From 0 to 24 months Measurement of Low-Density Lipoprotein Cholesterol (LDL-c) levels in millimoles per liter (mmol/L) using standardized laboratory procedures. Fasting blood samples will be collected at multiple time points within the 24-month period to assess changes over time.
Changes in High-Density Lipoprotein Cholesterol (HDL-c) over 24 Months From 0 to 24 months Measurement of High-Density Lipoprotein Cholesterol (HDL-c) levels in millimoles per liter (mmol/L) using standardized laboratory procedures. Fasting blood samples will be collected at multiple time points within the 24-month period to assess changes over time.
Changes in Body Weight over 24 Months From 0 to 24 months Measurement of body weight in kilograms (kg) at multiple time points within the 24-month period.
Changes in Body Fat Content over 24 Months From 0 to 24 months Measurement of body fat content as a percentage (%) of total body weight at multiple time points within the 24-month period.
Changes in Waist Circumference over 24 Months From 0 to 24 months Measurement of waist circumference in centimeters (cm) at multiple time points within the 24-month period.
Changes in Hip Circumference over 24 Months From 0 to 24 months Measurement of hip circumference in centimeters (cm) at multiple time points within the 24-month period.
Changes in C-peptide Levels over the First 6 Months From 0 to 6 months Measurement of C-peptide levels in nanomoles per liter (nmol/L) at multiple time points within the 6-month period.
Changes in Insulin Levels over the First 6 Months From 0 to 6 months Measurement of insulin levels in milliunits per liter (mU/L) at multiple time points within the 6-month period.
Major Adverse Cardiovascular Events From 0 to 24 months Major Adverse Cardiovascular Events (MACE) in the three study groups over 0-24 months.
Risk of Retinal Diseases From 0 to 24 months Risk of retinal diseases (e.g., diabetic retinopathy) in the three study groups over 0-24 months.
Trial Locations
- Locations (50)
Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University
🇨🇳Guanzhou, Guangdong, China
First Affiliated Hospital of Guangxi Medical University
🇨🇳Nanning, Guangxi, China
Southern Medical University
🇨🇳Guangzhou, Guangdong, China
North China University of Technology Affiliated Hospital
🇨🇳Tangshan, Hebei, China
Tongji Hospital
🇨🇳Wuhan, Hubei, China
Xiangya Hospital of Central South University
🇨🇳Changsha, Hunan, China
Second Affiliated Hospital of Nanchang University
🇨🇳Nanchang, Jiangsu, China
The Affiliated Hospital of Xuzhou Medical University
🇨🇳Xuzhou, Jiangsu, China
The First Affiliated Hospital with Nanjing Medical University,
🇨🇳Nanjing, Jiangsu, China
Dongying People's Hospital
🇨🇳Dongying, Shandong, China
Jinan Central Hospital
🇨🇳Jinan, Shandong, China
Shandong Provincial Hospital Affiliated to Shandong First Medical University
🇨🇳Jinan, Shandong, China
Liaocheng People's Hospital
🇨🇳Liaocheng, Shandong, China
Ningxia Medical University
🇨🇳Yinchuan, Ningxia, China
The Second Affiliated Hospital of Shandong First Medical University
🇨🇳Tai'an, Shandong, China
The Affiliated Hospital of Weifang Medical University
🇨🇳Weifang, Shandong, China
Weifang People's Hospital
🇨🇳Weifang, Shandong, China
Yantai Affiliated Hospital of Binzhou Medical University
🇨🇳Yantai, Shandong, China
First Affiliated Hospital of Wenzhou Medical University
🇨🇳Wenzhou, Zhejiang, China
Baoshan Hospital of Integrated Traditional Chinese and Western Medicine
🇨🇳Shanghai, China
Beijing Hospital
🇨🇳Beijing, China
Beijing Luhe Hospital
🇨🇳Beijing, China
Shanghai 10th People's Hospital
🇨🇳Shanghai, China
Shanghai Ninth People's Hospital Affiliated to Shanghai Jiao Tong University
🇨🇳Shanghai, China
The First Affiliated Hospital of University of Science and Technology of China
🇨🇳Hefei, Anhui, China
Beijing Chao Yang Hospital
🇨🇳Beijing, China
Shenzhen Second People's Hospital
🇨🇳Shenzhen, Guangdong, China
The Second Affiliated Hospital of Harbin Medical University
🇨🇳Ha'erbin, Heilongjiang, China
Wuxi People's Hospital
🇨🇳Wuxi, Jiangsu, China
First Affiliated Hospital of Zhengzhou University
🇨🇳Zhengzhou, Henan, China
Xiangyang Central Hospital
🇨🇳Xiangyang, Hubei, China
The First Affiliated Hospital of Nanchang University
🇨🇳Nanchang, Jiangxi, China
People's Hospital of Liaoning Province
🇨🇳Shenyang, Liaoning, China
Binzhou City Central Hospital
🇨🇳Binzhou, Shandong, China
Affiliated Hospital of Southwest Medical University
🇨🇳Luzhou, Sichuan, China
The Central Hospital of Lishui City
🇨🇳Lishui, Zhejiang, China
Chuzhou First People's Hospital
🇨🇳Chuzhou, Anhui, China
Fujian Medical University Union Hospital
🇨🇳Fuzhou, Fujian, China
LanZhou University
🇨🇳Lanzhou, Gansu, China
Fujian Provincial Hospital
🇨🇳Fuzhou, Fujian, China
Shunde Hospital of Southern Medical University
🇨🇳Foshan, Guangdong, China
Xinyang Central Hospital
🇨🇳Xinyang, Henan, China
The Second Affiliated Hospital of Baotou Medical College
🇨🇳Baotou, Inner Mongolia, China
The First Hospital of Jilin University
🇨🇳Changchun, Jilin, China
First Affiliated Hospital of China Medical University
🇨🇳Shenyang, Liaoning, China
First Affiliated Hospital of Xinjiang Medical University
🇨🇳Ürümqi, Xinjiang, China
Wenzhou Central Hospital
🇨🇳Wenzhou, Zhejiang, China
First Affiliated Hospital of Chongqing Medical University
🇨🇳Chongqing, China
Peking University Binhai Hospital
🇨🇳Tianjin, China
Tianjin First Central Hospital
🇨🇳Tianjin, China