Glucometabolic control of once-weekly dulaglutide switched from DPP4 inhibitor versus daily empagliflozin add-on in patients with type 2 diabetes inadequately controlled with metformin, sulfonylurea, and DPP4 inhibitor: A randomised trial

Aims: To compare the effectiveness and safety of empagliflozin and dulaglutide in patients with type 2 diabetes (T2D) inadequately controlled by oral triple therapy. Methods: In this 24-week, multi-center, randomized trial, patients with T2D and HbA_1c level ≥7.5% (58 mmol/mol) on metformin, sulfonylurea, and dipeptidyl peptidase 4 inhibitor (DPP4-i) were randomly assigned into two groups: daily empagliflozin add-on or once-weekly dulaglutide switched from DPP4-i. The primary endpoint was changes from baseline HbA_1c at 24 weeks. Results: In total, 152 patients were recruited to the empagliflozin-added quadruple group (n = 76) or the switched-to-dulaglutide triple group (n = 76). At week 24, both groups showed significant reduction in HbA1c level from baseline with greater reduction with empagliflozin (the mean treatment difference: –0.27% [95% CI –0.50 to –0.04, p = 0.024]) (–2.88 mmol/mol [95% CI –5.37 to –0.39], p = 0.024). Empagliflozin significantly reduced body weight from baseline to week 24 (–1.72 kg [95% CI –1.98 to –0.59, p < 0.001]). No serious adverse events were reported with either empagliflozin or dulaglutide. Conclusions: Empagliflozin, compared with once-weekly dulaglutide switched from DPP4-i, demonstrated greater HbA_1c reduction and weight loss in patients with T2D inadequately controlled with metformin, sulfonylurea, and DPP4-i. Trial registration: cris.nih.go.kr