Abstract 14623: SGLT2 Inhibitors versus Sulfonylureas as Add-On Therapy to Metformin in Type 2 Diabetes: A Systematic Review and Meta-Analysis

Abstract

Background: Traditionally, in patients with type 2 diabetes mellitus (T2DM) poorly controlled on metformin sulfonylureas were used as add-on therapy. Sodium glucose cotransporter 2 inhibitors (SGLT2i) have emerged as novel antidiabetic agents that have also shown improvement in cardiovascular outcomes. Aim: To conduct a meta-analysis comparing SGLT2i with sulfonylureas as add-on therapy to metformin in patients with poorly controlled type 2 diabetes mellitus (T2DM). Methods: We conducted a comprehensive search of PubMed, EMBASE, and Cochrane Library up till March 2023, to identify studies comparing SGLT2i versus sulfonylureas as add-on therapy to metformin in patients with poorly controlled T2DM (regardless of the presence of comorbid cardiovascular disease). Effect estimates were pooled using a random-effects model, and reported as risk ratios (RR) for dichotomous outcomes, and mean differences (MD) for continuous outcomes, along with 95% confidence intervals (CIs) for each. Results: Eleven studies met the inclusion criteria, all reporting mortality outcomes. Metformin-SGLT2i significantly reduced all-cause mortality (RR=0.76 [0.60, 0.95]; p=0.02; Figure ) and myocardial infarction (RR: 0.65 [0.47, 0.89]; p=0.008), in comparison to metformin-sulfonylureas. Metformin-SGLT2i was also associated with a significantly greater reduction in HbA1c (MD: -0.10% [-0.17 - -0.03]; p=0.004), fasting plasma glucose (MD: -0.55 [-0.69 - -0.41]; p<0.001), systolic blood pressure (MD: -4.77 mmHg [-5.39, -4.16]; p<0.001), and weight (MD: -4.57 kg [-4.74, -4.39]; p<0.00), compared with metformin-sulfonylurea. Moreover, metformin-SGLT2i was associated with a significantly lower risk of hypoglycemic events (RR=0.13 [0.10-0.17]; p<0.001). Conclusion: In patients with poorly controlled T2DM on metformin, addition of SGLT2i may yield superior outcomes compared with sulfonylureas.