Empagliflozin for the Treatment of Nonalcoholic Steatohepatitis in Patients with Type 2 Diabetes Mellitus

Background and Aims Sodium-glucose cotransporter-2 (SGLT2) inhibitors are a novel class of drugs that lower glucose by inducing renal glycosuria. We aimed to explore whether SGLT2 inhibitor added to the usual care for patients with type 2 diabetes mellitus (T2DM) and biopsy-proven nonalcoholic steatohepatitis (NASH) will benefit NASH histology. Methods In this investigator-initiated, single-arm, open-label, pilot study, nine biopsy-proven NASH patients with T2DM were given empagliflozin 25 mg daily for 24 weeks. Liver biopsy was repeated at the end of treatment. The histological outcomes were compared with the placebo group of a previous 48-week clinical trial. Results There was a significant reduction in body mass index (median change, Delta = -0.7 kg per m(2), p = 0.011), waist circumference (Delta = -3 cm, p = 0.033), systolic blood pressure (Delta = -9 mmHg, p = 0.024), diastolic blood pressure (Delta = -6 mmHg, p = 0.033), fasting blood glucose (Delta = -1.7 mmol/L, p = 0.008), total cholesterol (Delta = -0.5 mmol/L, p = 0.011), gamma glutamyl transpeptidase (Delta = -19 U/L, p = 0.013), volumetric liver fat fraction (Delta = -7.8%, p = 0.017), steatosis (Delta = -1, p = 0.014), ballooning (Delta = -1, p = 0.034), and fibrosis (Delta = 0, p = 0.046). All histological components either remained unchanged or improved, except in one patient who had worsening ballooning. Empagliflozin resulted in significantly greater improvements in steatosis (67% vs. 26%, p = 0.025), ballooning (78% vs. 34%, p = 0.024), and fibrosis (44% vs. 6%, p = 0.008) compared with historical placebo. Conclusion This pilot study provides primary histological evidence that empagliflozin may be useful for the treatment of NASH. This preliminary finding should prompt larger clinical trials to assess the effectiveness of empagliflozin and other SGLT2 inhibitors for the treatment of NASH in T2DM patients. Trial registry number ClincialTrials.gov number, NCT02964715.