Sodium-glucose co-transporter 2 inhibitors for type 2 diabetes mellitus: An overview for the primary care physician

Aims: Sodium-glucose co-transporter type 2 (SGLT2) inhibitors are a new class of anti-hyperglycaemic agents in type 2 diabetes mellitus (T2DM). This review examines their mechanism of action and provides an overview of safety and efficacy from the main studies of SGLT2 inhibitors marketed in the United States and Europe, namely, canagliflozin, dapagliflozin and empagliflozin. Methods: We searched the PubMed database to identify relevant publications on the mechanism of action of SGLT2 inhibitors and clinical trial reports. Results: Clinical trials in patients with T2DM have shown significant improvements in glycaemic control vs placebo with canagliflozin, dapagliflozin and empagliflozin: patients were more likely to reach target glycated haemoglobin levels compared with patients receiving placebo. All SGLT2 inhibitors also led to modest reductions in body weight and blood pressure vs placebo. Generally, all agents were well tolerated, with the most common adverse events with this class being genital mycotic infections and urinary tract infections. Hypoglycaemia was reported at rates similar to those seen with placebo, except when SGLT2 inhibitors were given in combination with insulin or an insulin secretagogue. Long-term outcome data are available only for empagliflozin: in the EMPA-REG OUTCOME study, empagliflozin demonstrated reduced risk of the composite end-point of 3-point major adverse cardiovascular events (cardiovascular death, non-fatal myocardial infarction or non-fatal stroke), primarily because of a significant reduction in cardiovascular mortality. Conclusions: SGLT2 inhibitors are an exciting addition to the list of available agents for T2DM, and may be suitable for various types of patients who need additional glycaemic control.