The safety and efficacy evaluation of sodium-glucose co-transporter 2 inhibitors for patients with non-alcoholic fatty liver disease: An updated meta-analysis

Abstract

Background: In recent years, sodium-glucose co-transporter 2 inhibitors (SGLT2is) have been increasingly used in the treatment of patients with non-alcoholic fatty liver disease (NAFLD). This updated metaanalysis aimed to evaluate the efficacy and safety of SGLT2is for patients with NAFLD. Methods: PubMed, Embase, Cochrane Library, Web of Science, Wan Fang, China National Knowledge Infrastructure and VIP databases were searched for relevant studies from inception to April 30, 2021. Values of weighted mean differences (WMDs) and risk ratios (RRs) were determined for continuous and dichotomous outcomes, respectively. Results: A total of 1,498 patients with NAFLD from 20 studies were included for further analysis. Pooled analyses indicated significant improvements in body mass index [WMD: −0.84 kg/m 2 , 95% CI ( −1.09, −0.60)], alanine aminotransferase [WMD: −4.36 U/L, 95% CI ( −7.17, −1.54)], aspartate aminotransferase [WMD: −2.94 U/L, 95% CI ( −5.33, −0.55)], fasting plasma glucose [WMD: −4.08 mmol/L, 95% CI ( −6.21, −1.95)] and fibrosis-4 index [WMD: −0.08, 95% CI ( −0.11, −0.05)] following SGLT2i treatment ( p < 0.01 for all above parameters). There was no significant difference in the incidence of total adverse events between the SGLT2i group and the control group (RR = 0.78, 95% CI (0.58, 1.06), p = 0.11]. Conclusion: SGLT2is seem to be a promising treatment for patients with NAFLD to improve metabolic and fibrosis indexes without increasing the incidence of adverse events. Most included studies were conducted in NAFLD patients with diabetes. Therefore, the results of this meta-analysis are more applicable to the diabetic population.

Effects of novel glucose-lowering drugs on the lipid parameters: A systematic review and meta-analysis

“…The primary line of care is weight reduction by adopting a healthy lifestyle (i.e., changes in diet and exercise). Unfortunately, weight loss by lifestyle changes alone is often a challenge for obese patients [ 8 ]. According to a study, fewer than half of patients can reduce their weight with lifestyle interventions alone [ 9 ].…”

Effects of SGLT2 inhibitors on hepatic fibrosis and steatosis: A systematic review and meta-analysis

“…SGLT2i could decrease hepatic fat content and liver enzymes and improve body composition in contrast to other antihyperglycemic drugs, independent of insulin resistance, plasma glucose, and weight loss (19,47). However, other investigations found that improvement in NAFLD is closely associated with body weight and plasma glucose (48,49). Hence, it is yet known whether the positive effects of SGLT2i on hepatic fibrosis and steatosis are attributed to a direct effect of SGLT2i or adjustments of metabolic disturbance.…”

SGLT-2 Inhibitors in NAFLD: Expanding Their Role beyond Diabetes and Cardioprotection

“…Of note, the overall improvement in hepatic steatosis is also found in patients treated with other classes of anti-diabetic drugs, like thiazolidinediones and dipeptidyl peptidase-4 (DPP-4) inhibitors, raising the question of steatosis improvement due to glycemic control [ 148 , 160 , 162 , 170 ]. Moreover, the vast majority of the aforementioned studies are limited by the small sample size, heterogenous inclusion criteria, especially regarding the presence of NAFLD, as well as the duration of follow up, thus meta-analyses have been conducted to better assess the true benefit of SGLT-2i in patients with DM and NAFLD [ 171 , 172 , 173 ]. In the largest one, comprising 9 randomized trials, with 7281 and 4088 patients in the SGLT-2i and control arm, (standard of care (SOC) or placebo), respectively, the use of SGLT-2i resulted in improvement of serum transaminases, body weight, and liver fat as measured by proton density fat fraction.…”