In patients with type 2 diabetes mellitus (T2DM) whose disease is not adequately controlled on metformin, sodium-glucose co-transporter 2 (SGLT2) inhibitors may have better long-term outcomes compared to sulfonylureas (Sus) as second-line therapy, according to a meta-analysis of RCTs in Clinical Drug Investigation. A search of PubMed, Embase, Cochrane Central Register of Controlled Trials, and ClinicalTrials.gov yielded five studies (n = 4,300) comparing SGLT2 inhibitors with SUs as add-on to metformin. SGLT2 inhibitors, compared to SUs, did not significantly change hemoglobin A1c (HbA1c) (mean difference [MD] − 0.06; 95% confidence interval [CI] [− 0.12, 0.08]), but were associated with less hypoglycemia (odds ratio [OR] 0.12; 95% CI [0.07, 0.21]). SGLT2 inhibitor patients lost about 3.5 kg, while SUs resulted in weight gain of about 1 kg (MD − 4.39; 95% CI [− 4.64, − 4.14]); SGLT2 inhibitor patients also had decreased blood pressure. However, SGLT2 inhibitors led to an increased risk for genital tract infections. When comparing HbA1c levels at baseline and 12–52 weeks, there were no significant between-group differences; however, at 104–208 weeks, SGLT2 inhibitors led to a greater reduction in HbA1c compared to SUs.
