SGLT2 Inhibitor and GLP-1 Receptor Agonist Co-Treatment: Liver Function Effects in Patients with Type 2 Diabetes Mellitus

Abstract

Purpose We evaluated the effects of sodium-glucose cotransporter inhibitors (SGLT2is) and GLP-1 receptor agonists (GLP1Ras) combination treatment in patients with type 2 diabetes mellitus (T2DM). Methods We retrospectively analyzed data for 643 patients with T2DM receiving SGLT2i + GLP1Ra combination treatment for at least one year (331 and 312 patients in the GLP1Ra- and SGLT2i-preceding groups, respectively). We used multiple imputation to generate replacement values for missing data, and thereafter, performed sensitivity analysis on the complete dataset. Propensity score matching was used to compare the effects of the preceding drugs on liver function. Results The mean AST/ALT values at baseline, at the initiation of combination treatment, and at final observation were 29.8 ± 20.0/37.7 ± 29.5, 28.7 ± 17.3/35.3 ± 6.0, and 26.0 ± 14.6/30.1 ± 21.6 IU/L, respectively, indicative of significant improvements in liver function (p < 0.001). Conversely, the FIB-4 index increased significantly from 1.28 ± 0.80 at baseline to 1.38 ± 0.83 (p < 0.001). Subgroup analysis showed no significant increases in FIB-4 index and ALT values for patients with baseline FIB-4 index ≥ 1.3 and ALT ≥ 30 IU/L. The matched model showed no significant differences in liver function or FIB-4 index after combination treatment between the SGLT2i- and GLP1Ra-preceding groups. Conclusion SGLT2i + GLP1Ra combination treatment significantly improved liver function and prevented FIB-4 index increases among patients with FIB-4 index ≥ 1.3. Further, even though the preceding drug did not affect liver function, prior use of SGLT2is appeared to be beneficial for improving liver function.