Dapagliflozin‐Associated Reduction in Liver Fat Is Independent of Weight Loss in Patients With Type 2 Diabetes

OBJECTIVE: This study aimed to investigate the association between SGLT2 inhibitor (dapagliflozin) use in patients with type 2 diabetes (T2D) and changes in body weight and liver fat. METHODS: This is a secondary analysis of a randomized placebo-controlled trial. Fifty-six patients with T2D were randomized to placebo or 10 mg dapagliflozin. Anthropometrics, liver MRI-proton density fat fraction (PDFF), fasting glucose, HbA1c, and liver function tests were measured at baseline and at 12 months. The relationship between dapagliflozin use and changes in body weight and liver fat was investigated using multiple linear regression models and mediation analysis. RESULTS: In this cohort, 76% of participants had hepatic steatosis. Groups were similar in cardiometabolic risk factors and in liver fat fraction values. Compared to placebo, dapagliflozin resulted in reduction in liver MRI-PDFF (-3.7% vs. 0.5%, p = 0.001), body weight (-3.84 vs. -1.42 kg, p = 0.015), and HbA1c (-0.52 vs. 0.11, p = 0.012). Mediation analysis confirmed the direct effect of the SGLT2 inhibitor on change in liver fat and showed that the indirect effect of weight loss on change in liver fat was not statistically significant. CONCLUSIONS: Twelve months of dapagliflozin was associated with a significant reduction in liver fat as measured by MRI-PDFF compared to placebo; this effect was independent of weight loss and other known beneficial metabolic effects of SGLT2 inhibition. TRIAL REGISTRATION: ClinicalTrials.gov: NCT03782259.