Type 2 diabetes (T2D) in Asian Indians is characterized by high ectopic fat deposition in liver and pancreas, elevated Fetuin-A (an insulin resistance mediator), and hepatic fibrosis risk. While SGLT2 inhibitors like Dapagliflozin (DAPA) reduce hepatic and pancreatic fat, Metformin’s effects on these parameters, especially Fetuin-A and fibrosis, remain underexplored in this population.
In this paired prospective intervention without controls, 45 Asian Indian T2D patients (aged 18-65 years, HbA1c 7-10%) received either Metformin 1000 mg/day (n=15) or DAPA 10 mg/day (n=30) for 120 days. Assessments at baseline and endpoint included anthropometry, body composition (DEXA), insulin resistance surrogates (HOMA-IR), serum Fetuin-A (ELISA), hepatic fat fraction (HFF) and pancreatic fat fraction (PFF) via MRI-proton density fat fraction (MRI-PDFF), and hepatic fibrosis via vibration-controlled transient elastography (VCTE) for controlled attenuation parameter (CAP) and stiffness (kPa). Changes were analyzed using paired t-tests or Wilcoxon signed-rank tests (p<0.05 significant). Sample size ensured 97% power to detect meaningful changes.
Both interventions yielded significant reductions in body weight (-3.2 kg Metformin; -4.1 kg DAPA), BMI, body fat percentage, waist/hip circumferences, and HOMA-IR (all p<0.01). Fetuin-A decreased markedly with Metformin (from 250±45 to 180±32 ng/mL, p=0.002) and DAPA (from 265±50 to 195±38 ng/mL, p<0.001)—a novel finding for DAPA. VCTE showed reduced CAP (Metformin: 285±42 to 245±35 dB/m, p=0.01; DAPA: 292±48 to 248±40 dB/m, p<0.001) and kPa (Metformin: 7.2±1.5 to 5.8±1.2 kPa, p=0.003; DAPA: 7.5±1.6 to 6.0±1.3 kPa, p<0.001), indicating fibrosis improvement. However, Metformin did not alter HFF (12.5±4.2% to 11.8±3.9%, p=0.42) or PFF (8.3±2.1% to 7.9±2.0%, p=0.31), contrasting prior DAPA data showing reductions.
Metformin and DAPA independently lower Fetuin-A and hepatic fibrosis in Asian Indian T2D patients, with shared benefits on adiposity and insulin sensitivity. Metformin’s lack of effect on organ fat highlights complementary roles: pair it with SGLT2 inhibitors for comprehensive ectopic fat targeting. These insights inform personalized therapy to mitigate T2D complications in high-risk South Asians.
