Written by Babatunde Carew
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When compared to DPP-4 inhibitors, SGLT-2 inhibitors were associated with a reduced risk of cirrhosis in patients with type 2 diabetes (T2DM), while GLP-1 receptor agonists showed no risk reduction.
SGLT2s save the liver, GLP1s don’t deliver?
According to the ADA, up to 70% of patients with T2DM have coexisting metabolic dysfunction-associated steatotic liver disease (MASLD). As the authors highlight, studies have shown that SGLT2 inhibitors and GLP1RAs reduce hepatic steatosis, but further data are needed to determine their effect on the cirrhosis pathway in patients with diabetes. This population-based cohort study investigated whether GLP-1RAs and SGLT-2 inhibitors reduce the risk of cirrhosis in T2DM patients compared to DPP-4 inhibitors. SGLT-2 inhibitors demonstrated a 36% risk reduction in cirrhosis incidence (HR 0.64, 95%CI 0.46–0.90), while GLP-1RAs showed no significant change in cirrhosis incidence (HR 0.90, 95%CI 0.68–1.19). In general, GLP1RAs tend to be prescribed to patients with worse glycemic control and more advanced diabetes than SGLT2 inhibitors, given their more potent effect. A clear limitation in this study is that the GLP1RA cohort had more: obesity (91.1% vs 70%), A1c over 8 (72.5% vs 69.9%), and microvascular complications than the SGLT2i group. Further, since patients were not screened for hepatic steatosis with imaging prior to study enrollment, there may have been a higher rate of pre-existing unidentified MASLD than is noted. Finally, the authors point out that this study should not be interpreted as a head-to-head comparison between GLP-1RAs and SGLT2 inhibitors given the study design.
How does this change my practice?
This study changes my current practice. In patients with MASLD and T2DM, I typically prescribe GLP1RAs preferentially, given their well-documented effect on decreasing hepatic steatosis. I may lean to SGLT2is more often in those without other significant indications for GLP1RA in the future. Future studies examining the effect of dual GIP/GLP1RA, such as tirzepatide, in this population would be interesting.
Source
Glucagon-Like Peptide 1 Receptor Agonists and Sodium-Glucose Cotransporter 2 Inhibitors and the Prevention of Cirrhosis Among Patients With Type 2 Diabetes. Diabetes Care. 2025 Jan 8:dc241903. doi: 10.2337/dc24-1903. Epub ahead of print. PMID: 39774820
