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

Overview

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.

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.