Liver function effects of SGLT2 inhibitor and GLP-1 receptor agonist combination treatment in patients with type 2 diabetes (post hoc analysis of RECAP study).

Aim: The favor effect on liver disease by odium-glucose cotransporter inhibitor (SGLT2i) and GLP-1 receptor agonist (GLP1Ra) was reported; however, the effect of the combination treatment of these drugs was not well known.

Methods: We retrospectively analyzed data for 643 patients with type 2 diabetes receiving SGLT2i + GLP1Ra combination treatment for at least 1 year (331 and 312 patients in the GLP1Ra- and SGLT2i-preceding groups, respectively). Propensity score (PS) matching was used to compare the effects of the preceding drugs on liver function.

Results: The mean AST and ALT values at baseline, at the initiation of combination treatment, and at final observation were 29.8 ± 20.0 and 37.7 ± 29.5, 28.7 ± 17.3 and 35.3 ± 6.0, 26.0 ± 14.6 and 30.1 ± 21.6 IU/L, respectively, indicative of significant improvements in liver function (P < 0.001). Conversely, significant progress in the fibrosis-4 (FIB-4) index category was observed even after the combination treatment (P = 0.03). Subgroup analysis revealed that a significant decrease in ALT was observed only in patients with a baseline ALT ≥30 IU/L after the combination treatment (P = 0.005). Improvement of the FIB-4 index category was observed in patients in the baseline FIB-4 index ≥2.6 group and in the 1.3 ≤FIB-4 index <2.6 group (46% and 19%, respectively). The matched model showed no significant differences in liver function after combination treatment between the SGLT2i- and GLP1Ra-preceding groups.

Conclusions: SGLT2i + GLP1Ra combination treatment significantly improved liver dysfunction and prevented the progression of FIB-4 index category among patients with an FIB-4 index ≥1.3.