Canagliflozin extends life span and leads to less weight gain in C57BL6 male mice

Abstract

ABSTRACTSGLT2 inhibitors are widely prescribed drugs for type 2 diabetes and heart failure. It seems that their beneficial health effects are multifaceted and not only limited to the amelioration of glycemic profile. It is suggested that SGLT2 inhibitors-induced glycosuria causes a metabolic shift that mimics the fasting response. It is also known that calorie restriction leads to enhanced longevity in mice. Thus, we hypothesized that long-term treatment of mice with SGLT2 inhibitors might extend their life span. To this end male C57BL6 mice at the age of 4 months were put on a normal chow diet or on a diet supplemented with 200 mg/kg canagliflozin. The canagliflozin-treated mice showed lower body weight gain over time and increased life span. The median survival of control mice was 107.5 weeks, while that of the canagliflozin-treated group was 112.5 weeks (p=0.011). No difference was seen in the presence or severity of cataracts. This study showed for the first time an enhanced median survival of canagliflozin-treated male mice with a homogeneous genetic background (C57BL6). Further analyses are in progress to elucidate the metabolic adaptations and mechanisms underlying this effect.