Henagliflozin's Impact on Prediabetes Remission

Type 2 Diabetes Clinical Trial

Official title:

Effect of Henagliflozin on the Remission of Prediabetes Population: A National Multicenter, Randomized Controlled Study

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT06448130
• Other study ID #: MA-DM-IV-004
• Status: Not yet recruiting
• Phase: Phase 4
• Start date: June 2024
• Est. completion date: December 2027

Study information

• Verified date: June 2024
• Source: Shandong Provincial Hospital
• Contact: Xiude Fan, MD&PhD
• Phone: +8613186067538
• Email: fanxiudexjtu[@]163.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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 information / eligibility

• Status: Not yet recruiting
• Enrollment: 984
• Est. completion date: December 2027
• Est. primary completion date: December 2026
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 65 Years

Eligibility

Inclusion Criteria:

1. Male or female subjects between the ages of 18 and 65 years;

2. Individuals without hypoglycemic therapy before, including hypoglycemic drugs or traditional Chinese medicine formulations with hypoglycemic effects;

3. 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%;

4. Individuals willing to provide written informed consent and can comply with study procedures and follow-up.

Exclusion Criteria:

1. Allergic to Henagliflozin;

2. Previously diagnosed with diabetes;

3. HbA1c = 6.5% or FPG = 7.0 mmol/L or PPG = 11.1 mmol/L;

4. Use of GLP-1 receptor agonists, orlistat, or other weight-reducing drugs in the past 3 months;

5. Fluctuation in weight by 5% or more in the past month;

6. 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);

7. Untreated hyperthyroidism or hypothyroidism, excluding those with normal thyroid function after treatment;

8. 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);

9. 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;

10. Other obesity caused by endocrine disorders, such as Cushing's syndrome;

11. Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) levels > 3 times of the upper limit of the normal range (UNL);

12. eGFR less than 30 mL/min/1.73 m2, severe kidney damage, end-stage renal disease or requiring dialysis;

13. Significant cardiovascular diseases including myocardial infarction, congestive heart failure (=grade III New York Heart Association), left ventricular ejection fraction=40%, or cerebrovascular accidents;

14. Impaired consciousness and various mental health disorders;

15. Malignant tumors and other serious illnesses;

16. Pregnant or breast-feeding or planning pregnancy within 24 months;

17. Enrolled in another clinical trial currently or within the 3 months prior to enrollment;

18. 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).

Related Conditions & MeSH terms

• Diabetes Mellitus, Type 2
• Glucose Intolerance
• Glucose Metabolism Disorders
• Metabolic Diseases
• PreDiabetes
• Prediabetic State
• Type 2 Diabetes

Intervention

Drug:
• Henagliflozin 5mg
Henagliflozin 5mg + lifestyle intervention
• Henagliflozin 10mg
Henagliflozin 10mg+ lifestyle intervention
• Placebo
Placebo+ lifestyle intervention

Locations

Country	Name	City	State
China	The Second Affiliated Hospital of Baotou Medical College	Baotou	Inner Mongolia
China	Beijing Chao Yang Hospital	Beijing
China	Beijing Hospital	Beijing
China	Beijing Luhe Hospital	Beijing
China	Binzhou City Central Hospital	Binzhou	Shandong
China	The First Hospital of Jilin University	Changchun	Jilin
China	Xiangya Hospital of Central South University	Changsha	Hunan
China	First Affiliated Hospital of Chongqing Medical University	Chongqing
China	Chuzhou First People's Hospital	Chuzhou	Anhui
China	Dongying People's Hospital	Dongying	Shandong
China	Shunde Hospital of Southern Medical University	Foshan	Guangdong
China	Fujian Medical University Union Hospital	Fuzhou	Fujian
China	Fujian Provincial Hospital	Fuzhou	Fujian
China	Southern Medical University	Guangzhou	Guangdong
China	Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University	Guanzhou	Guangdong
China	The Second Affiliated Hospital of Harbin Medical University	Ha'erbin	Heilongjiang
China	The First Affiliated Hospital of University of Science and Technology of China	Hefei	Anhui
China	Jinan Central Hospital	Jinan	Shandong
China	Shandong Provincial Hospital Affiliated to Shandong First Medical University	Jinan	Shandong
China	LanZhou University	Lanzhou	Gansu
China	Liaocheng People's Hospital	Liaocheng	Shandong
China	The Central Hospital of Lishui City	Lishui	Zhejiang
China	Affiliated Hospital of Southwest Medical University	Luzhou	Sichuan
China	Second Affiliated Hospital of Nanchang University	Nanchang	Jiangsu
China	The First Affiliated Hospital of Nanchang University	Nanchang	Jiangxi
China	The First Affiliated Hospital with Nanjing Medical University,	Nanjing	Jiangsu
China	First Affiliated Hospital of Guangxi Medical University	Nanning	Guangxi
China	Baoshan Hospital of Integrated Traditional Chinese and Western Medicine	Shanghai
China	Shanghai 10th People's Hospital	Shanghai
China	Shanghai Ninth People's Hospital Affiliated to Shanghai Jiao Tong University	Shanghai
China	First Affiliated Hospital of China Medical University	Shenyang	Liaoning
China	People's Hospital of Liaoning Province	Shenyang	Liaoning
China	Shenzhen Second People's Hospital	Shenzhen	Guangdong
China	The Second Affiliated Hospital of Shandong First Medical University	Tai'an	Shandong
China	North China University of Technology Affiliated Hospital	Tangshan	Hebei
China	Peking University Binhai Hospital	Tianjin
China	Tianjin First Central Hospital	Tianjin
China	First Affiliated Hospital of Xinjiang Medical University	Ürümqi	Xinjiang
China	The Affiliated Hospital of Weifang Medical University	Weifang	Shandong
China	Weifang People's Hospital	Weifang	Shandong
China	First Affiliated Hospital of Wenzhou Medical University	Wenzhou	Zhejiang
China	Wenzhou Central Hospital	Wenzhou	Zhejiang
China	Tongji Hospital	Wuhan	Hubei
China	Wuxi People's Hospital	Wuxi	Jiangsu
China	Xiangyang Central Hospital	Xiangyang	Hubei
China	Xinyang Central Hospital	Xinyang	Henan
China	The Affiliated Hospital of Xuzhou Medical University	Xuzhou	Jiangsu
China	Yantai Affiliated Hospital of Binzhou Medical University	Yantai	Shandong
China	Ningxia Medical University	Yinchuan	Ningxia
China	First Affiliated Hospital of Zhengzhou University	Zhengzhou	Henan

Sponsors (1)

Lead Sponsor	Collaborator
Shandong Provincial Hospital

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Normoglycemia Achievement Rates Post-6-Month Intervention	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).	From 6 months post-intervention to 12 months
Secondary	Blood Glucose Control Normalization	Proportion and duration of normalization of blood glucose levels within 24 months in the three study groups.	From 6 months post-intervention to 24 months
Secondary	Incidence of New-Onset Type 2 Diabetes	Incidence of new-onset type 2 diabetes within 24 months in the three study groups.	From 0 to 24 months
Secondary	Changes in HbA1c Levels	Changes in HbA1c levels over the 24-month period in the three study groups.	From 0 to 24 months
Secondary	Impact of Glycemic Status at 12 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.	From 12 months to 24 months
Secondary	Changes in blood pressure over 24 Months	Changes in systolic and diastolic blood pressure in the three study groups over 24 Months.	From 0 to 24 months
Secondary	Changes in serum uric acid levels over 24 Months	Changes in serum uric acid levels in the three study groups over 24 Months.	From 0 to 24 months
Secondary	Changes in hepatic steatosis over 24 Months	Changes in hepatic steatosis assessed by abdominal ultrasound in the three study groups over 24 Months.	From 0 to 24 months
Secondary	Changes in carotid intima-media thickness over 24 Months	Changes in carotid intima-media thickness measured by carotid ultrasound in the three study groups over 24 Months.	From 0 to 24 months
Secondary	Changes in Total Cholesterol (TC) over 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.	From 0 to 24 months
Secondary	Changes in Triglycerides (TG) over 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.	From 0 to 24 months
Secondary	Changes in Low-Density Lipoprotein Cholesterol (LDL-c) over 24 Month	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.	From 0 to 24 months
Secondary	Changes in High-Density Lipoprotein Cholesterol (HDL-c) over 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.	From 0 to 24 months
Secondary	Changes in Body Weight over 24 Months	Measurement of body weight in kilograms (kg) at multiple time points within the 24-month period.	From 0 to 24 months
Secondary	Changes in Body Mass Index (BMI) over 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.	From 0 to 24 months
Secondary	Changes in Body Fat Content over 24 Months	Measurement of body fat content as a percentage (%) of total body weight at multiple time points within the 24-month period.	From 0 to 24 months
Secondary	Changes in Waist Circumference over 24 Months	Measurement of waist circumference in centimeters (cm) at multiple time points within the 24-month period.	From 0 to 24 months
Secondary	Changes in Hip Circumference over 24 Months	Measurement of hip circumference in centimeters (cm) at multiple time points within the 24-month period.	From 0 to 24 months
Secondary	Changes in C-peptide Levels over the First 6 Months	Measurement of C-peptide levels in nanomoles per liter (nmol/L) at multiple time points within the 6-month period.	From 0 to 6 months
Secondary	Changes in Insulin Levels over the First 6 Months	Measurement of insulin levels in milliunits per liter (mU/L) at multiple time points within the 6-month period.	From 0 to 6 months
Secondary	Major Adverse Cardiovascular Events	Major Adverse Cardiovascular Events (MACE) in the three study groups over 0-24 months.	From 0 to 24 months
Secondary	Risk of Retinal Diseases	Risk of retinal diseases (e.g., diabetic retinopathy) in the three study groups over 0-24 months.	From 0 to 24 months
Secondary	Risk of Renal diseases	Risk of renal diseases (e.g., diabetic nephropathy/chronic kidney disease) in the three study groups over 0-24 months.	From 0 to 24 months