Efficacy and safety of sodium-glucose cotransporter 2 inhibitors as add-on to metformin and sulfonylurea treatment for the management of type 2 diabetes: a meta-analysis.

This study evaluates the efficacy and safety of sodium-glucose cotransporter 2 (SGLT2) inhibitors as add-on to metformin and sulfonylurea treatment for type 2 diabetes management. The literature search was conducted in electronic databases and meta-analyses of mean differences in the changes from baseline in selected disease endpoints (efficacy endpoints) or odds ratios (for safety endpoints) were performed to compare outcomes between SGLT2 inhibitor- and placebo-/comparator-treatments. Seven studies (5,143 patients; age 56.75 years [95% CI: 56.19, 57.37]; body mass index 29.53 kg/m [28.23, 30.83]; and 51.87% [50.46, 53.57] males) were included. Compared to placebo, SGLT2 inhibitors significantly (p < 0.00001) reduced glycated hemoglobin (HbA1c; -0.79% [95% CI: -0.90, -0.68]), fasting plasma glucose (FPG; -1.73 mmol/L [-1.86, -1.60]) and body weight (-1.85 kg [-2.11, -1.59]) after 52-78 weeks of treatment. There were no significant differences in reduction of either HbA1c, FPG or body weight between 18-24 weeks and after 52-76 weeks of treatment. Treatment with SGLT2 inhibitors as add-on to metformin and sulfonylurea was also associated with significant reductions in blood pressure and triglycerides and increase in high-density lipoprotein-cholesterol. Incidence of hypoglycemia was significantly higher, but incidence of hyperglycemia was significantly lower in SGLT2 inhibitor group. Overall, drug-related adverse events were more common in SGLT2 group mainly due to higher incidence of genital tract infections.