Adverse Liver and Renal Outcomes After Initiating SGLT‐2i and GLP‐1RA Therapy Among Patients With Diabetes and MASLD

CONTEXT: The management of metabolic dysfunction-associated steatotic liver disease (MASLD) and type 2 diabetes mellitus (T2DM) presents a significant clinical challenge, with a focus on preventing progression to liver and renal complications. OBJECTIVE: To evaluate the liver and renal outcomes among new users of sodium-glucose cotransporter 2 inhibitors (SGLT2i) versus glucagon-like peptide-1 receptor agonists (GLP-1RA), dipeptidyl peptidase-4 inhibitors (DPP4i) and other anti-diabetic medications in patients with MASLD and T2DM. DESIGN: Retrospective cohort study. SETTING: Electronic health records. PARTICIPANTS: A total number of 88 306 patients with MASLD and T2DM were included in a propensity score-matched analysis comparing the effects of anti-diabetic drugs. INTERVENTION: Patients were categorized into groups based on their initiation of anti-diabetic medications. MAIN OUTCOME MEASURES: The primary outcomes were the incidence of cirrhosis, hepatic decompensations, and hepatocellular carcinoma. Secondary outcomes were a progression of chronic kidney disease (CKD), severity of CKD stages, and the need for hemodialysis. RESULTS: In the SGLT2i versus DPP4i, a reduced risk of cirrhosis was observed in the SGLT2i (HR: 0.97), along with fewer hepatic decompensations (HR: 0.84) and a lower incidence of HCC (HR: 0.50). CKD progression, particularly to stages 4-5, was significantly lower in the SGLT2i (HR: 0.53), as was hemodialysis (HR: 0.38). However, SGLT2i exhibited a slightly lower risk of CKD progression (HR: 0.77) and a reduced need for hemodialysis (HR: 0.71) compared to the GLP-1RA, while there was no difference in hepatic outcomes between the GLP-1RA and SGLT2i. CONCLUSIONS: SGLT2 inhibitors in patients with MASLD and T2DM demonstrated reduced risks of liver complications and a favorable impact on renal outcomes. These findings support the preferential consideration of SGLT2i in managing this patient population, particularly for mitigating the progression of liver and kidney diseases.