OBJECTIVE: This open-label study investigated potential drug-drug interactions between empagliflozin and metformin. METHODS: 16 healthy men received treatment A (empagliflozin 50 mg q.d. for 5 days), treatment B (empagliflozin 50 mg q.d. for 4 days with metformin 1,000 mg b.i.d. for 3 days and 1,000 mg q.d. on Day 4) and treatment C (metformin 1,000 mg b.i.d. for 3 days and 1,000 mg q.d .on Day 4) in the sequence AB then C, or C then AB. RESULTS: Metformin had no clinically relevant effect on the area under the steady state plasma concentration-time curve (AUC(τ,ss) geometric mean ratio (GMR): 96.9; 90% CI: 92.3 - 101.7) or the maximum plasma concentration at steady state (C(max,ss) GMR: 100.5; 90% CI: 88.8 - 113.7) of empagliflozin. Similarly, empagliflozin had no clinically relevant effect on AUC(τ,ss) (GMR: 100.7; 90% CI: 95.9 - 105.6) or C(max,ss) (GMR: 103.6; 90% CI: 96.5 - 111.2) of metformin. The renal clearance of empagliflozin and metformin were unaffected by co-administration. Both drugs were well tolerated alone and in combination and did not cause hypoglycemia. CONCLUSIONS: These data support co-administration of empagliflozin and metformin without dose adjustment.
OBJECTIVE: This open-label study investigated potential drug-drug interactions between empagliflozin and metformin. METHODS: 16 healthy men received treatment A (empagliflozin 50 mg q.d. for 5 days), treatment B (empagliflozin 50 mg q.d. for 4 days with metformin 1,000 mg b.i.d. for 3 days and 1,000 mg q.d. on Day 4) and treatment C (metformin 1,000 mg b.i.d. for 3 days and 1,000 mg q.d .on Day 4) in the sequence AB then C, or C then AB. RESULTS:Metformin had no clinically relevant effect on the area under the steady state plasma concentration-time curve (AUC(τ,ss) geometric mean ratio (GMR): 96.9; 90% CI: 92.3 - 101.7) or the maximum plasma concentration at steady state (C(max,ss) GMR: 100.5; 90% CI: 88.8 - 113.7) of empagliflozin. Similarly, empagliflozin had no clinically relevant effect on AUC(τ,ss) (GMR: 100.7; 90% CI: 95.9 - 105.6) or C(max,ss) (GMR: 103.6; 90% CI: 96.5 - 111.2) of metformin. The renal clearance of empagliflozin and metformin were unaffected by co-administration. Both drugs were well tolerated alone and in combination and did not cause hypoglycemia. CONCLUSIONS: These data support co-administration of empagliflozin and metformin without dose adjustment.
Authors: Vikas Kumar Dawra; David L Cutler; Susan Zhou; Rajesh Krishna; Haihong Shi; Yali Liang; Christine Alvey; Anne Hickman; Didier Saur; Steven G Terra; Vaishali Sahasrabudhe Journal: Clin Pharmacol Drug Dev Date: 2018-05-22