Timothy Garvey, Luc Van Gaal, Lawrence A. Leiter, Ujjwala Vijapurkar, James List, Robert Cuddihy, Jimmy Ren, Michael J. Davies

Metabolism. 2018. doi: 10.1016/j.metabol.2018.02.002

Type 2 diabetic patients with increased visceral fat mass and insulin resistance are at a higher risk for cardiovascular disease and premature death. The increased visceral fat impairs adipose tissue function and is the result of combinatorial processes, including increased macrophage recruitment (MCP-1 production), increased inflammatory cytokines (IL-6 and TNF-a secretion), and reduced anti-inflammatory factors (adipokine and adiponectin).

Canagliflozin is a sodium glucose co-transporter 2 inhibitor that significantly lowered HbA1c and lowered incidences of hypoglycemia compared to glimepiride (sulfonylurea). In addition, canagliflozin demonstrated cardio- and renoprotective effects. This post hoc analysis accessed the effects of canagliflozin (300mg) compared to glimepiride on adipokines, inflammatory biomarkers, and chemokines that are associated with impaired adipose tissue function, insulin resistance, and cardiovascular disease in type 2 diabetic patients.

Decreases in HbA1c and body weight are similar in patients treated with canagliflozin and glimepiride and are consistent with the observations in the overall study population. Serum adiponectin was analyzed using the xMAP (Multi-Analyte Profiling) technology platform. Serum levels of IL-6 and TNF-a were measured using the ultra-high-sensitivity assay, single molecule array (Simoa). Patients receiving canagliflozin demonstrated a significant increase in adiponectin and a decrease in IL-6 compared to those taking glimepiride.

Taken together, these indicate that canagliflozin improve adipose tissue function to reduce cardiovascular events in type 2 diabetics.