SGLT2 inhibitors: New medicines for addressing unmet needs in type 2 diabetes.

Abstract

The prevalence of type 2 diabetes mellitus (T2DM) is rising in Australia. Sodium glucose co-transporter 2 (SGLT2) inhibitors are an emerging treatment for T2DM. SGLT2 inhibitors offer a novel approach to lowering hyperglycaemia by suppressing renal glucose reabsorption and increasing urinary glucose excretion. The increased urinary glucose excretion has also been associated with caloric loss and osmotic diuresis. Dapagliflozin and canagliflozin are the SGLT2 inhibitors that are approved for clinical use in the US, the European Union (EU), and Australia. Their use results in reductions in HbA1c and body weight across a broad range of patient populations ranging from drug-naive patients to those who require additional therapy due to inadequate glycaemic control on their existing treatment. In addition, reductions in blood pressure (BP), particularly systolic BP, have also been noted. SGLT2 inhibitors are generally well tolerated with low rates of adverse events. Episodes of hypoglycaemia were mostly classified as minor, with low and balanced rates of severe hypoglycaemia across studies. The proportions of patients with genital infections and urinary tract infections were higher with dapagliflozin and canagliflozin versus their comparators. However, these infections were generally mild-to-moderate in intensity, treated with standard antimicrobial therapies, and rarely led to discontinuation. No dosage adjustments for dapagliflozin and canagliflozin are recommended for normal-to-mild renal impairment. Dapagliflozin and canagliflozin are not recommended for use in patients with eGFR<60 and <45mL/min/1.73m(2), respectively. Overall, SGLT2 inhibitors have shown the potential to become an important addition to the treatment armamentarium for effective management of patients with T2DM.