Metabolic Dysfunction-Associated Steatotic Liver Disease, Type 2 Diabetes
Conditions
Keywords
Dapagliflozin, Metformin, Serum IGF-1, Type 2 Diabetes Mellitus, Metabolic Dysfunction-Associated Steatotic Liver Disease
Brief summary
This is a 3-month, single-center, prospective, randomized, parallel-controlled, open-label trial investigating the effects of metformin combined with dapagliflozin on serum IGF-1 levels in male patients with type 2 diabetes mellitus (T2DM) and metabolic dysfunction-associated steatotic liver disease (MASLD). A total of 84 eligible male patients (aged 30-60 years, HbA1c 7.0%-10.0%, CAP ≥248 dB/m, on stable metformin monotherapy for ≥8 weeks) will be randomized 1:1 to either continue metformin alone or receive metformin plus dapagliflozin 10 mg/day for 12 weeks. The primary endpoint is the change in serum IGF-1 from baseline to 3 months between groups. Secondary endpoints include changes in hepatic steatosis (CAP), liver stiffness (LSM), FIB-4 index, metabolic parameters, and safety outcomes. The study aims to determine whether adding dapagliflozin to metformin can restore the suppressed GH-IGF-1 axis and provide mechanistic insights into its hepatoprotective effects.
Detailed description
Screening & Enrollment (-1 to 0 week): Male T2DM patients on stable metformin (≥1500 mg/d) for ≥8 weeks are screened. CAP measurement via FibroScan® confirms MASLD (≥248 dB/m). Eligible patients provide written informed consent. Baseline & Randomization (Day 0): Comprehensive assessments include demographics, physical exam, laboratory tests (FPG, HbA1c, insulin, HOMA-IR, liver/renal function, lipids, hsCRP), serum IGF-1/IGFBP3, and FibroScan® (CAP/LSM). Patients are then randomized 1:1 to control (metformin alone) or experimental (metformin + dapagliflozin 10 mg/d) groups. Follow-up (Weeks 4 and 12): At Week 4, patients undergo physical exam, FPG, HbA1c, liver/renal function tests, adverse event recording, and adherence assessment. At Week 12, all baseline assessments are repeated, including IGF-1/IGFBP3 and FibroScan®, to evaluate changes from baseline. Data Analysis (Weeks 13-24): Data are double-entered, cleaned, and locked. Primary analysis compares ΔIGF-1 between groups using t-test/Mann-Whitney U test with ANCOVA adjustment. Secondary endpoints, correlations, and subgroup analyses are performed. All tests are two-sided with significance at P \< 0.05 using SPSS or R software.
Interventions
DRUGMetformin + Dapagliflozin
Maintain the stable pre-enrollment dose of metformin (≥1500 mg/day or maximum tolerated dose) plus dapagliflozin 10 mg/day orally, administered once daily before breakfast, for 3 consecutive months. Other concomitant medications (e.g., antihypertensives, lipid-lowering agents) for both groups should remain unchanged during the study period unless clinically necessary adjustments are required. Patients should be instructed to maintain stable dietary and exercise habits throughout the study.
DRUGMetformin
Maintain the stable pre-enrollment dose of metformin monotherapy (≥1500 mg/day or maximum tolerated dose) for 3 consecutive months. Other concomitant medications (e.g., antihypertensives, lipid-lowering agents) for both groups should remain unchanged during the study period unless clinically necessary adjustments are required. Patients should be instructed to maintain stable dietary and exercise habits throughout the study.
Sponsors
The 95th Hospital of Putian，Putian, Fujian, China
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
MALE
Age
30 Years to 60 Years
Healthy volunteers
No
Inclusion criteria
1. Males aged 30-60 years; 2. Meeting the WHO diagnostic criteria for type 2 diabetes mellitus, with HbA1c levels between 7.0% and 10.0%; 3. Having received a stable dose of metformin (≥1500 mg/day or the maximum tolerated dose) as monotherapy for at least 8 weeks; 4. Meeting the diagnostic criteria for MASLD: Controlled Attenuation Parameter (CAP) value ≥248 dB/m detected, with the presence of at least one cardiometabolic risk factor; 5. No prior use of SGLT2 inhibitors, insulin secretagogues, insulin, or GLP-1 receptor agonists; 6. Willing to participate voluntarily and sign the informed consent form.
Exclusion criteria
1. Type 1 diabetes mellitus or other specific types of diabetes; 2. Weekly alcohol intake exceeding 210g for males; 3. Concomitant chronic liver diseases (viral hepatitis, autoimmune liver disease, Wilson's disease, hemochromatosis, etc.); 4. Known pituitary or hypothalamic diseases affecting the GH-IGF-1 axis; 5. Previous or current use of GH preparations or IGF-1 preparations; 6. Baseline estimated glomerular filtration rate (eGFR) \<45 mL/min/1.73m²; 7. Previous diagnosis of cardiovascular diseases (coronary heart disease, stroke, heart failure) or severe liver diseases (decompensated cirrhosis); 8. Active malignant tumors; 9. Allergy to dapagliflozin or similar drugs; 10. Use of medications affecting IGF-1 levels (such as oral estrogens, high-dose glucocorticoids) within the past 3 months; 11. Diabetic ketoacidosis, severe infection, or surgical stress within 1 month prior to enrollment.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| ΔIGF-1 | 12 weeks | The difference in the change value of serum IGF-1 levels (ΔIGF-1) from baseline to 3 months between the two groups. |
| Changes in non-invasive indicators of liver fibrosis | 12 weeks | Differences in the change values of the FIB-4 index from baseline to 3 months between the two groups |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Changes in liver fat content | 12 weeks | Differences in the change value of CAP (ΔCAP) from baseline to 3 months between the two groups |
| Changes in non-invasive indicators of liver fibrosis | 12 weeks | Differences in the change values of LSM from baseline to 3 months between the two groups |
| ΔIGF-1/IGFBP3 molar ratio | 12 weeks | Differences in changes in the IGF-1/IGFBP3 molar ratio between the two groups |
| Changes in glucose metabolism indicators | 12 weeks | Differences in HbA1c between the two groups |
| ΔBMI | 12 weeks | Differences in changes in BMI between the two groups |
| Changes in liver function indicators | 12 weeks | Differences in ALT, AST, and GGT between the two groups |
Countries
China
Contacts
CONTACTRongfeng Zhu, Dr
STUDY_CHAIRRongfeng Zhu
The 95th Hospital of Putian
Outcome results
None listed