Efficacy and safety of sodium glucose co‐transport‐2 inhibitors in type 2 diabetes: a meta‐analysis of randomized clinical trials

Aims Sodium glucose co‐transport‐2 ( SGLT ‐2) inhibitors, a new class of glucose‐lowering agents, reduce tubular glucose reabsorption, producing a reduction of blood glucose without stimulating insulin release. The aim of the present meta‐analysis is the assessment of the overall efficacy and safety profile of these drugs. Methods A meta‐analysis was performed including all trials with a duration of at least 12 weeks, comparing a SGLT ‐2 inhibitor with a non‐ SGLT ‐2 inhibitor agent in type 2 diabetes. The principal outcome of this analysis was the effect of SGLT ‐2 inhibitors on HbA1c at 12, 24 and 52 weeks. Hypoglycaemia, genital and urinary infections were retrieved and combined to calculate Mantel–Haenszel odds ratio ( MH‐OR ). Furthermore, data on body mass index (BMI), endpoint fasting plasma glucose, systolic and diastolic blood pressure, creatinine, hematocrit and lipid profile were collected. Results Among placebo‐controlled trials, HbA1c reduction at 12, 24 and 52 weeks was 0.5 [0.4; 0.6], 0.6 [0.6; 0.5] and 0.6 [0.7; 0.5]%. In placebo‐controlled studies, 24‐week reduction of HbA1c with SGLT ‐2 inhibitors was greater in trials enrolling patients with a lower mean age and duration of diabetes, and a higher baseline BMI , HbA1c and fasting glucose. In placebo‐controlled trials, SGLT ‐2 inhibitors determined a weight loss during the first 24 weeks, which was maintained up to 52 weeks. Conclusions SGLT ‐2 inhibitors are effective in the treatment of type 2 diabetes, providing additional benefits, such as weight loss, reduction of blood pressure and increase in high‐density lipoprotein ( HDL )‐cholesterol. Apart from genital and urinary infections, rather frequent but usually mild, SGLT ‐2 inhibitors appear to be well tolerated.