Benefits of combining SGLT2 inhibitors and pioglitazone on risk of MASH in type 2 diabetes—A real‐world study

Abstract Aims Both pioglitazone and glucagon‐like peptide 1 receptor agonists (GLP1RA) alone improve metabolic dysfunction‐associated steatohepatitis (MASH) in randomized clinical trials, whereas preclinical studies suggested MASH benefits with sodium glucose co‐transporter 2 inhibitors (SGLT2i). In the real world, patients with type 2 diabetes often require multiple agents for glycaemic control. Here, we investigated the benefits of combining these agents on risks of MASH. Materials and Methods Longitudinal changes in FibroScan‐aspartate aminotransferase (FAST) score were measured in 888 patients with type 2 diabetes. Use of pioglitazone, GLP1RA and/or SGLT2i was defined as continuous prescriptions of ≥180 days prior to their last reassessment FibroScan. Multivariable logistic regression analysis was conducted to evaluate the associations between use of these agents and FAST score changes. Results Over a median follow‐up of 3.9 years, the increasing number of these agents used was significantly associated with more reductions in FAST score ( p for trend <0.01). Dual combination was independently associated with a higher likelihood of achieving low FAST score at reassessment than single use of any of these agents (odds ratio [OR] 2.84, p = 0.01). Among the different drug combinations, using SGLT2i and pioglitazone (median dose 15 mg daily) together, as compared to not using any of these three agents, was associated with a higher likelihood of both low FAST score at reassessment (OR 6.51, p = 0.008) and FAST score regression (OR 12.52, p = 0.009), after adjusting for changes in glycaemic control and body weight during the study. Conclusions Combining SGLT2i and pioglitazone is a potentially useful strategy to ameliorate ‘at‐risk’ MASH in patients with type 2 diabetes.