Sodium-Glucose Cotransporter-2 Inhibitor Use and Risk of Liver-Related Events in Patients with Type 2 Diabetes: A Meta-Analysis of Observational Cohort Studies

<p dir="ltr"><b>Background: </b>The effect of sodium-glucose cotransporter-2 (SGLT2) inhibitors on the risk of major adverse liver-related outcomes (MALOs) is uncertain.</p><p dir="ltr"><b>Purpose</b>: We performed a meta-analysis of observational cohort studies to quantify the magnitude of the association between SGLT-2-inhibitor use and risk of developing MALOs in people with type 2 diabetes (T2DM).</p><p dir="ltr"><b>Data Sources:</b> We systematically reviewed three large electronic databases from inception to January 2025.</p><p dir="ltr"><b>Study Selection: </b>We included<b> </b>active-comparator, new-user cohort studies comparing SGLT-2-inhibitor use versus other glucose-lowering medications in patients with T2DM.</p><p dir="ltr"><b>Data Extraction: </b>The primary outcome was the incidence rate of MALOs defined as a composite of hepatic decompensation events, hepatocellular carcinoma, liver transplantation, or liver-related deaths. Secondary outcomes included each of the above as individual events. Meta-analysis was performed using random-effects models.</p><p dir="ltr"><b>Data Synthesis: </b>We identified eight cohort studies with aggregate data on 626,104 patients with T2DM (397,806 SGLT2-inhibitor new-users and 228,298 new users of other glucose-lowering agents). During a median of 2.7 years, SGLT-2-inhibitor use was<b> </b>associated with a significantly lower risk of MALOs (random-effects HR 0.83, 95%CI 0.72-0.95; <i>I</i>^<em>2</em>=83.1%) and liver-related deaths (random-effects HR 0.64, 95%CI 0.50-0.82; <i>I</i>^<em>2</em>=0%). The significant risk reduction in MALOs was observed when SGLT-2-inhibitor use was compared to DPP-4 inhibitors, metformin, or pioglitazone but not GLP-1 receptor agonists. Sensitivity analyses did not modify these results. The funnel plot did not show significant publication bias.</p><p dir="ltr"><b>Limitations</b>: Observational design of the cohort studies and high level of heterogeneity.</p><p dir="ltr"><b>Conclusions: </b>SGLT-2-inhibitor use was associated with a lower risk of MALOs in patients with T2DM.</p>