The effects of dapagliflozin on hepatic and visceral fat in type 2 diabetes patients with non‐alcoholic fatty liver disease

Abstract

Background and Aim: Sodium-glucose cotransporter 2 inhibitors have shown excellent results in glucose control in type 2 diabetes mellitus (T2DM) patients, while also promoting weight loss. These mechanisms may be beneficial in the treatment of non-alcoholic fatty liver disease (NAFLD). Our study aims to investigate the effect of dapagliflozin on hepatic and visceral fat contents and related biochemical markers in T2DM with NAFLD patients. Methods: This is a double-blinded placebo-controlled randomized, single-center study. Non-insulin-dependent T2DM patients with NAFLD were prospectively enrolled and randomly assigned to receive either dapagliflozin (10 mg/day) or placebo for 12 weeks. The primary end-point was the changes in intrahepatic lipid contents, evaluated by the liver attenuation index. Results: Of 40 patients enrolled, 38 patients completed the study (dapagliflozin group, n = 18; placebo group, n = 20). Baseline demographic and laboratory findings were similar in both groups. After 12 weeks of treatment, dapagliflozin significantly decreased intrahepatic lipid contents demonstrated by an increase in liver attenuation index in comparison with the placebo treatment (5.8 ± 5.1 vs 0.5 ± 6.1 Hounsfield units, P = 0.006). Significant reduction in bodyweight, bodyfat, visceral fat/subcutaneous fat ratio, hemoglobin A1c, and alanine aminotransferase were also observed in the dapagliflozin-treated group as compared with the placebo group (all P < 0.05). There was no significant difference in adipokines including adiponectin, leptin, and tumor necrosis factor-α changes between the dapagliflozin-treated group and the placebo group (all P = nonsignificant). Conclusion: Dapagliflozin treatment for 12 weeks is associated with improvement in hepatic fat content, a decrease in visceral fat and bodyweight, enhanced glycemic control, and improved liver biochemistry among T2DM patients with NAFLD.* P < 0.05, comparison of baseline and post-treatment data within groups.

Efficacy and safety of oral semaglutide in patients with non‐alcoholic fatty liver disease complicated by type 2 diabetes mellitus: A pilot study

“…In general, lifestyle modifications for weight reduction and treatment of extrahepatic comorbidities take precedence over direct NAFLD treatment. 8 , 9 , 10 Recently, anti‐diabetic drugs, such as glucagon‐like peptide‐1 receptor agonists (GLP‐1 RAs) 11 , 12 , 13 and sodium/glucose cotransporter 2 inhibitors (SGLT2‐Is), 14 , 15 , 16 , 17 , 18 , 19 , 20 have been investigated as effective drugs for NAFLD treatment.…”

Adipokines in Non-Alcoholic Fatty Liver Disease: Are We on the Road toward New Biomarkers and Therapeutic Targets?

“…The effect of SGLT2 on adipokine levels was poorly explored in clinical trials with NAFLD patients. A study verified no significant differences in adiponectin and leptin levels in the dapagliflozin-treated group compared to the placebo group [ 157 ], whereas the lower serum level of high-molecular-weight adiponectin was correlated with an improved response to dapagliflozin in T2DM patients with NAFLD [ 156 ]. Altogether, SGLT2 inhibitors seem to be an interesting therapeutic option for T2DM patients with NAFLD, but clinicians need to consider their efficacy and safety when individualizing the treatment [ 156 ].…”

Influence of Sodium-Glucose Cotransporter-2 Inhibitors on Plasma Adiponectin in Patients with Type 2 Diabetes: A Meta-Analysis of Randomized Controlled Trials

“…Since three studies included multiple dose groups of SGLT-2 inhibitors, these datasets were included in the meta-analysis as independent comparisons [22,23,25]. The studies included in the meta-analysis were published between 2012 and 2021, and performed in Japan [23][24][25][26][27][28][29], China [30], Thailand [35], the United Kingdom [22], Italy [31], Sweden [32], Germany [33], and the United States [34]. Various SGLT-2 inhibitors were used in these studies, such as dapagliflozin, tofogliflozin, luseogliflozin, ipragliflozin, empagliflozin, and canagliflozin.…”

“…Accordingly, it has been proposed that the benefits of SGLT-2 inhibitors on cardiorenal outcomes in patients with T2DM may be related to the increased plasma adiponectin following the treatment [21]. However, previous randomized controlled trials (RCTs) evaluating the effect of SGLT2 inhibitors on plasma level of adiponectin in patients with T2DM showed inconsistent results [22][23][24][25][26][27][28][29][30][31][32][33][34][35]. Although a previous meta-analysis suggested that SGLT-2 inhibitors were associated with an increment of plasma adiponectin [36] in T2DM patients, only ten studies published before 2018 were included, and the recent published RCTs were not included [32][33][34][35].…”

“…However, previous randomized controlled trials (RCTs) evaluating the effect of SGLT2 inhibitors on plasma level of adiponectin in patients with T2DM showed inconsistent results [22][23][24][25][26][27][28][29][30][31][32][33][34][35]. Although a previous meta-analysis suggested that SGLT-2 inhibitors were associated with an increment of plasma adiponectin [36] in T2DM patients, only ten studies published before 2018 were included, and the recent published RCTs were not included [32][33][34][35]. Besides, the significant heterogeneity of the metaanalysis made the results difficult to be interpreted.…”