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

Abstract

AbstractThe influence of sodium-glucose cotransporter-2 (SGLT-2) inhibitors on plasma adiponectin remains not comprehensively evaluated. We performed a meta-analysis to systematically evaluate the effect of SGLT2 inhibitors on plasma level of adiponectin in patients with type 2 diabetes mellitus (T2DM). Randomized controlled trials comparing SGLT-2 inhibitors with non-active controls on plasma adiponectin in T2DM patients were retrieved by search of the Medline (PubMed), Embase, and CENTER (Cochrane Library) databases from inception to April 5, 2022. Study characteristics and outcome data were independently extracted by two authors. A random-effect model by incorporating the potential between-study heterogeneity was used to combine the results. Fourteen studies with 2142 patients contributed to the meta-analysis. Compared to placebo, SGLT-2 inhibitors significantly increased plasma adiponectin [standard mean difference (SMD): 0.35, 95% CI: 0.24 to 0.46, p<0.001] with mild heterogeneity (I2=19%). Predefined subgroup analyses suggested that tofogliflozin (SMD: 0.37, p<0.001), luseogliflozin (SMD: 0.51, p<0.001), and ipragliflozin (SMD: 0.34, p<0.001) were associated with increased adiponectin, but not for dapagliflozin (SMD: 0.14, p 0.26). In addition, SGLT-2 inhibitors were associated with increased adiponectin in studies from Asia (SMD: 0.42, p<0.001), but not in studies from the western countries (SMD: 0.16, p 0.17). Moreover, the increment of adiponectin was more significant in patients with body mass index (BMI)<30 kg/m2 (SMD: 0.46, p<0.001) than that in patients with BMI≤30 kg/m2 (SMD: 0.19, p 0.02, p for subgroup difference 0.01). In conclusion, SGLT-2 inhibitors could significantly increase plasma adiponectin as compared with placebo in T2DM patients.