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.
Highlights
Nonalcoholic fatty liver disease (NAFLD) is a common comorbidity of type 2 diabetes mellitus (T2DM) and one half to two thirds of T2DM patients have NAFLD [1]
Since weight reduction is the main strategy for decreasing hepatic steatosis, it may be postulated that Sodium-glucose cotransporter 2 inhibitors (SGLT2is) have potential for the management of T2DM-associated NAFLD
Before Propensity score (PS) matching, the SGLT2i group (n = 102) was significantly younger and had higher body weight and body mass index (BMI) compared with the non-SGLT2i control group (n = 663)
Summary
Nonalcoholic fatty liver disease (NAFLD) is a common comorbidity of type 2 diabetes mellitus (T2DM) and one half to two thirds of T2DM patients have NAFLD [1]. In a recent phase 4 study (n = 84), empagliflozin 25 mg/day for 24 weeks reduced liver fat content by 22% as measured by magnetic resonance imaging (MRI) in European patients with T2DM [13]. After treatment for 24 weeks with 2.5 mg luseogliflozin, another SGLT2i, the MRI-PDFF was reduced significantly from 21.5 ± 7.2% to 15.7 ± 6.8% in Japanese patients with T2DM (n = 40) [15]. In another European study (n = 32), treatment with dapagliflozin 10 mg/day for 8 weeks significantly decreased liver MRI-PDFF by 13% in patients with T2DM [16] These findings suggest that SGLT2is may have additional benefit of improving steatosis in T2DM-associated NAFLD
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