Metformin-Dapagliflozin Effects on IGF-1 in Male T2DM With MASLD

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.

Inclusion criteria

• Males aged 30-60 years;
• Meeting the WHO diagnostic criteria for type 2 diabetes mellitus, with HbA1c levels between 7.0% and 10.0%;
• Having received a stable dose of metformin (≥1500 mg/day or the maximum tolerated dose) as monotherapy for at least 8 weeks;
• 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;
• No prior use of SGLT2 inhibitors, insulin secretagogues, insulin, or GLP-1 receptor agonists;
• Willing to participate voluntarily and sign the informed consent form.

Exclusion criteria

• Type 1 diabetes mellitus or other specific types of diabetes;
• Weekly alcohol intake exceeding 210g for males;
• Concomitant chronic liver diseases (viral hepatitis, autoimmune liver disease, Wilson's disease, hemochromatosis, etc.);
• Known pituitary or hypothalamic diseases affecting the GH-IGF-1 axis;
• Previous or current use of GH preparations or IGF-1 preparations;
• Baseline estimated glomerular filtration rate (eGFR) <45 mL/min/1.73m²;
• Previous diagnosis of cardiovascular diseases (coronary heart disease, stroke, heart failure) or severe liver diseases (decompensated cirrhosis);
• Active malignant tumors;
• Allergy to dapagliflozin or similar drugs;
• Use of medications affecting IGF-1 levels (such as oral estrogens, high-dose glucocorticoids) within the past 3 months;
• Diabetic ketoacidosis, severe infection, or surgical stress within 1 month prior to enrollment.