Glucose Metabolism Disorders, PreDiabetes, Prediabetic State, Type 2 Diabetes
Conditions
Keywords
Prediabetes management, Henagliflozin, SGLT2 inhibitors, Lifestyle interventions, Type 2 diabetes prevention, Glucose Metabolism Disorders, Metabolic Diseases
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.
Interventions
DRUGHenagliflozin 5mg
Henagliflozin 5mg + lifestyle intervention
DRUGHenagliflozin 10mg
Henagliflozin 10mg+ lifestyle intervention
DRUGPlacebo
Placebo+ lifestyle intervention
Sponsors
Shandong Provincial Hospital
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 65 Years
Healthy volunteers
No
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).
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| Changes in HbA1c Levels | From 0 to 24 months | Changes in HbA1c levels over the 24-month period in the three study groups. |
| 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. |
| 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 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 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 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. |
| 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. |
| 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. |
| 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 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. |
| 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. |
| 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 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. |
Countries
China
Contacts
Primary ContactXiude Fan, MD&PhD
Backup ContactJunming Han, PhD
Outcome results
None listed