Sodium-Glucose Transport Protein-2 Inhibitors in the Treatment of Non-alcoholic Steatohepatitis: An Evidence-Based Review

Abstract

Context: Globally, the prevalence of non-alcoholic steatohepatitis (NASH) is increasing, leading to a substantial economic burden and becoming one of the most common reasons for liver transplantation. The lack of effective therapeutic interventions to reduce disease progression makes NASH a major global healthcare problem in both developing and developed countries. This evidence-based review reports studies that evaluated the effectiveness of different sodium-glucose transport protein-2 (SGLT-2) inhibitors in treating NASH. Evidence Acquisition: We conducted a detailed literature search for research studies evaluating the effectiveness of SGLT-2 inhibitors in managing NASH. Relevant literature was gathered from databases including PubMed, EMBASE, and LILACS by applying appropriate keywords to obtain published research articles between January 2014 and June 2024. We focused on clinical studies involving human participants that administered different SGLT-2 inhibitors and evaluated their efficacy in managing NASH. Results: We retrieved 409 articles from all the databases; however, after reviewing all the full-text articles, we found that only four research articles reported the evaluation of SGLT-2 drugs studied in different clinical trials to assess their efficacy in NASH. Among the evaluated drugs, dapagliflozin, licogliflozin, canagliflozin, ertugliflozin, and empagliflozin have been potentially evaluated in reducing non-alcoholic fatty liver disease (NAFLD) and NASH associated with type 2 diabetes mellitus (T2DM). The selected SGLT-2 inhibitors reduced Body Mass Index (BMI), waist circumference, blood pressure, total cholesterol, and gamma-glutamyl transpeptidase, followed by a volumetric liver fat fraction. Single studies of empagliflozin, licogliflozin, dapagliflozin, and canagliflozin showed promising results. Conclusions: This review provides a detailed update on the recent SGLT-2 inhibitors evaluated for treating NASH. However, a controlled clinical trial with sufficient NASH patient samples and a larger follow-up is required to establish the therapeutic potential of SGLT-2 inhibitors before they are approved for NASH patients.