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

Abstract

The 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.

Comparative effectiveness of sodium‐glucose co‐transporter‐2 inhibitors and dipeptidyl peptidase‐4 inhibitors on liver function in patients with type 2 diabetes in Japan: A real‐world data analysis

“…19 Furthermore, in a Taiwanese database study of patients with T2D, ALT reduction from baseline was also significantly greater in patients receiving an SGLT2i than in those receiving a DPP4i (mean difference: -4.0 IU/L; P < .001), with a similar HbA1c reduction between the groups. 20 These results may be explained by the SGLT2i-specific effects, including increased gluconeogenesis and hepatic glucose production, 21 adiponectin [22][23][24] and hepatic β-oxidation. 25 SGLT2is inhibit hepatocyte death and attenuation of abnormal oxidative and inflammatory responses, 26 and may contribute to maintaining or improving albumin synthesis.…”

Non-alcoholic fatty liver disease: from understanding risk factors to finding optimal treatment regimens: A review

“…Ингибиторы НГЛТ-2 повышают уровень адипонектина в плазме у пациентов СД 2. При этом прирост адипонектина являлся более значительным у пациентов с индексом массы тела (ИМТ) <30 кг/м 2 [84].…”

The Role of Adipokines in Inflammatory Mechanisms of Obesity

“…Another widely used group of preparations in the treatment of type 2 diabetes is sodium glucose-like transporter 2 inhibitors (SGLT-2). The meta-analysis dedicated to reviewing the influence of sodium–glucose cotransporter-2 inhibitors on plasma adiponectin levels revealed significantly increased plasma adiponectin in type 2 diabetic patients administered tofogliflozin, luseogliflozin, and ipragliflozin, but not dapagliflozin [ 145 ]. In another study, dapagliflozin was shown to downregulate circulating leptin levels in patients with type 2 diabetes and class 3 obesity during a 1-year administration [ 146 ].…”