INTRODUCTION: This randomized, open-label, crossover study investigated potential drug-drug interactions between the sodium glucose cotransporter-2 (SGLT-2) inhibitor empagliflozin and the dipeptidyl peptidase-4 (DPP-4) inhibitor sitagliptin. Empagliflozin is a potent and selective SGLT-2 inhibitor that lowers blood glucose levels by inhibiting renal glucose reabsorption, leading to an increase in urinary glucose excretion. Sitagliptin lowers blood glucose through an insulin-dependent mechanism of action. METHODS:Sixteen healthy male volunteers received three treatments (A, B, C) in one of two treatment sequences (AB then C, or C then AB). In treatment AB, 50 mg empagliflozin was administered once daily (q.d.) for 5 days (treatment A), immediately followed by coadministration of 50 mg empagliflozin q.d. and 100 mg sitagliptin q.d. over 5 days (treatment B). In treatment C, 100 mg sitagliptin was administered q.d. for 5 days. A washout period of ≥7 days separated treatments AB and C. RESULTS: Coadministration of sitagliptin with empagliflozin did not have a clinically relevant effect on the area under the concentration-time curve of the analyte in plasma at steady state over a uniform dosing interval τ (AUC(τ,ss)) (geometric mean ratio [GMR] 110.4; 90% confidence interval [CI] 103.9, 117.3) or maximum measured concentration of the analyte in plasma at steady state over a uniform dosing interval τ (C (max,ss)) (GMR 107.6; 90% CI 97.0, 119.4) of empagliflozin. Coadministration of empagliflozin with sitagliptin did not have a clinically meaningful effect on the AUC(τ,ss) (GMR 103.1; 90% CI 98.9, 107.3) or C (max,ss) (GMR 108.5; 90% CI 100.7, 116.9) of sitagliptin. Empagliflozin and sitagliptin were well tolerated when given alone or in combination. Five subjects (31.3%) reported at least one adverse event (AE): three (18.8%) experienced an AE while receiving empagliflozin monotherapy and three (18.8%) while receiving sitagliptin monotherapy. No adverse events were reported during the coadministration period. No AEs were regarded as drug-related by the investigator. CONCLUSION: These results indicate that empagliflozin and sitagliptin can be coadministered without dose adjustments.
RCT Entities:
INTRODUCTION: This randomized, open-label, crossover study investigated potential drug-drug interactions between the sodium glucose cotransporter-2 (SGLT-2) inhibitor empagliflozin and the dipeptidyl peptidase-4 (DPP-4) inhibitor sitagliptin. Empagliflozin is a potent and selective SGLT-2 inhibitor that lowers blood glucose levels by inhibiting renal glucose reabsorption, leading to an increase in urinary glucose excretion. Sitagliptin lowers blood glucose through an insulin-dependent mechanism of action. METHODS: Sixteen healthy male volunteers received three treatments (A, B, C) in one of two treatment sequences (AB then C, or C then AB). In treatment AB, 50 mg empagliflozin was administered once daily (q.d.) for 5 days (treatment A), immediately followed by coadministration of 50 mg empagliflozin q.d. and 100 mg sitagliptin q.d. over 5 days (treatment B). In treatment C, 100 mg sitagliptin was administered q.d. for 5 days. A washout period of ≥7 days separated treatments AB and C. RESULTS: Coadministration of sitagliptin with empagliflozin did not have a clinically relevant effect on the area under the concentration-time curve of the analyte in plasma at steady state over a uniform dosing interval τ (AUC(τ,ss)) (geometric mean ratio [GMR] 110.4; 90% confidence interval [CI] 103.9, 117.3) or maximum measured concentration of the analyte in plasma at steady state over a uniform dosing interval τ (C (max,ss)) (GMR 107.6; 90% CI 97.0, 119.4) of empagliflozin. Coadministration of empagliflozin with sitagliptin did not have a clinically meaningful effect on the AUC(τ,ss) (GMR 103.1; 90% CI 98.9, 107.3) or C (max,ss) (GMR 108.5; 90% CI 100.7, 116.9) of sitagliptin. Empagliflozin and sitagliptin were well tolerated when given alone or in combination. Five subjects (31.3%) reported at least one adverse event (AE): three (18.8%) experienced an AE while receiving empagliflozin monotherapy and three (18.8%) while receiving sitagliptin monotherapy. No adverse events were reported during the coadministration period. No AEs were regarded as drug-related by the investigator. CONCLUSION: These results indicate that empagliflozin and sitagliptin can be coadministered without dose adjustments.
Authors: Simon A Hawley; Rebecca J Ford; Brennan K Smith; Graeme J Gowans; Sarah J Mancini; Ryan D Pitt; Emily A Day; Ian P Salt; Gregory R Steinberg; D Grahame Hardie Journal: Diabetes Date: 2016-07-05 Impact factor: 9.461