Sodium-Glucose Cotransporter-2 Inhibitors Ameliorate Liver Enzyme Abnormalities in Korean Patients With Type 2 Diabetes Mellitus and Nonalcoholic Fatty Liver Disease

Abstract

Sodium-glucose cotransporter-2 inhibitors (SGLT2is) are reported to reduce body fat in patients with type 2 diabetes mellitus (T2DM), and SGLT2i-induced weight reduction may help improve comorbid nonalcoholic fatty liver disease (NAFLD). This study aimed to investigate the potential benefit of SGLT2is over other oral antidiabetic drugs (OADs) in patients with T2DM-associated NAFLD. We enrolled real-world Korean patients with T2DM-associated NAFLD in whom initial metformin therapy had been modified by stepwise addition of OAD(s) due to insufficient glucose control. Propensity score (PS) matching was used for the comparison of changes in clinical and biochemical parameters to balance potential covariates. Among the 765 enrolled patients, 663 patients received additional OADs other than SGLT2i and 102 patients received SGLT2i therapy. PS matching selected 150 and 100 patients from the control and the SGLT2i group, respectively. The SGLT2i group lost more weight than the control group at 6 months (mean -1.3 kg vs. 0.0 kg; P < 0.001). Alanine aminotransferase (ALT) levels also decreased more in the SGLT2i group at 3 (-11 U/L vs. -1 U/L), 6 (-12 U/L vs. -1 U/L), and 12 months (-14 U/L vs. -2 U/L) (all P < 0.05). Addition of SGLT2is was an independent predictor of ALT improvement in a multivariate logistic regression model (odds ratio 1.91; P = 0.016). Compared with other OADs, addition of SGLT2is was more effective in weight reduction and ALT improvement in patients with T2DM and comorbid NAFLD.

Keywords: alanine aminotransferase; body weight; propensity score (PS) matching (PSM); sodium-glucose cotransporter 2 (SGLT2) inhibitor; type 2 diabetes mellitus.

Figure 1

Flowchart of the selection process. *Other liver diseases included viral hepatitis B and C, autoimmune hepatitis, drug-induced liver injury, and history of excessive alcohol intake (daily intake > 30 g for men and > 20 g for women). GLP-1, glucagon-like peptide-1; US, ultrasound; SGLT2i, sodium-glucose cotransporter-2 inhibitor.

Figure 2

Sensitivity analysis of odds ratio of SGLT2is for managing ALT levels. This Forest plot indicates the odds ratio of SGLT2i over control for the endpoint of ALT decrease ≥ 15% of baseline values. The benefit of SGLT2i for ALT decrease was more prominent in younger patients, male sex, high baseline BMI, and patients with less weight reduction.