Long-term effectiveness and safety of quadruple combination therapy with empagliflozin versus dapagliflozin in patients with type 2 diabetes: 3-year prospective observational study

Aims: To investigate the long-term effectiveness and safety of two distinct sodium-glucose co-transporter 2 (SGLT2) inhibitors, empagliflozin and dapagliflozin, in inadequately controlled type 2 diabetes (T2D) despite a combined administration of metformin, glimepiride and dipeptidyl peptidase-4 inhibitor. Methods: A total of 362 patients with T2D were enrolled for this 3-year open-label, prospective observational study. Empagliflozin (25 mg/day, n = 185) or dapagliflozin (10 mg/day, n = 177) was added to the existing triple drug regimen. HbA1c, fasting plasma glucose (FPG), body weight, and other cardiometabolic variables and adverse events were evaluated. Results: At 3 years, changes in HbA1c and FPG were-1.7% (standard error [SE] 0.10) and-60.0 mg/dL(2.2), and-1.1%(0.12) and-48.1 mg/dL(3.6), for empagliflozin and dapagliflozin group, respectively (P = 0.001 and P = 0.055). Empagliflozin group showed significantly greater body weight reduction (-4.5 kg [SE 0.35] vs.-1.0 kg [SE 0.40], P = 0.024) and had beneficial effects on HDL cholesterol and LDL cholesterol (both P < 0.05). The overall incidence of adverse events, cardiovascular events and mortality did not differ between the two groups. Conclusions: Quadruple combination therapy with either empagliflozin or dapagliflozin showed a positive long-term effect in the glycemic control and body weight reduction with generally well tolerance. In general, the use of empagliflozin performed better than dapagliflozin. Clinical Trial Number NCT03748810 (ClinicalTrials.gov). (c) 2021 The Authors. Published by Elsevier B.V. This is an open access article under the CC BY NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).