BACKGROUND:Empagliflozin is an oral, potent, and selective inhibitor of sodium glucose cotransporter 2, inhibition of which reduces renal glucose reabsorption and results in increased urinary glucose excretion. Linagliptin is an oral inhibitor of dipeptidyl peptidase-4 approved for the treatment of type 2 diabetes in the United States, Europe, Japan, and Canada. Due to their complementary modes of action, there is a good rationale to combine empagliflozin with linagliptin to improve glycemic control in patients with type 2 diabetes. OBJECTIVE: This study was conducted to investigate the pharmacokinetics of empagliflozin and linagliptin after coadministration in healthy volunteers. METHODS: This was an open-label, randomized, multiple-dose, crossover study with 3 treatments in 2 treatment sequences. Sixteen healthy male subjects received treatment A (empagliflozin 50 mg once daily [QD] for 5 days), treatment B (empagliflozin 50 mg QD and linagliptin 5 mg QD for 7 days), and treatment C (linagliptin 5 mg QD for 7 days) in sequence AB then C, or sequence C then AB. RESULTS:Sixteen healthy male subjects aged between 18 and 50 years with a body mass index of 18.5 to 29.9 kg/m(2) were included in the study. Linagliptin total exposure (AUC over a uniform dosing interval τ at steady state geometric mean ratio [GMR], 1.03 [90% CI, 0.96-1.11]) and peak exposure (C(max) at steady state GMR, 1.01 [90% CI, 0.87-1.19) exposure was unaffected by coadministration of empagliflozin. Empagliflozin total exposure (AUC over a uniform dosing interval τ at steady state GMR, 1.02 [90% CI, 0.97-1.07]) was unaffected by coadministration of linagliptin. There was a reduction in empagliflozin peak exposure (C(max) at steady state GMR, 0.88 [90% CI, 0.79-0.99]) when linagliptin was coadministered that was not considered clinically meaningful. No adverse events were reported during the coadministration period. No hypoglycemia was reported. Empagliflozin and linagliptin were well tolerated. CONCLUSION: These data support the coadministration of empagliflozin and linagliptin without dose adjustments. European Union Drug Regulating Authorities Clinical Trials Registration: EudraCT 2008-006089-27.
RCT Entities:
BACKGROUND:Empagliflozin is an oral, potent, and selective inhibitor of sodium glucose cotransporter 2, inhibition of which reduces renal glucose reabsorption and results in increased urinary glucose excretion. Linagliptin is an oral inhibitor of dipeptidyl peptidase-4 approved for the treatment of type 2 diabetes in the United States, Europe, Japan, and Canada. Due to their complementary modes of action, there is a good rationale to combine empagliflozin with linagliptin to improve glycemic control in patients with type 2 diabetes. OBJECTIVE: This study was conducted to investigate the pharmacokinetics of empagliflozin and linagliptin after coadministration in healthy volunteers. METHODS: This was an open-label, randomized, multiple-dose, crossover study with 3 treatments in 2 treatment sequences. Sixteen healthy male subjects received treatment A (empagliflozin 50 mg once daily [QD] for 5 days), treatment B (empagliflozin 50 mg QD and linagliptin 5 mg QD for 7 days), and treatment C (linagliptin 5 mg QD for 7 days) in sequence AB then C, or sequence C then AB. RESULTS: Sixteen healthy male subjects aged between 18 and 50 years with a body mass index of 18.5 to 29.9 kg/m(2) were included in the study. Linagliptin total exposure (AUC over a uniform dosing interval τ at steady state geometric mean ratio [GMR], 1.03 [90% CI, 0.96-1.11]) and peak exposure (C(max) at steady state GMR, 1.01 [90% CI, 0.87-1.19) exposure was unaffected by coadministration of empagliflozin. Empagliflozin total exposure (AUC over a uniform dosing interval τ at steady state GMR, 1.02 [90% CI, 0.97-1.07]) was unaffected by coadministration of linagliptin. There was a reduction in empagliflozin peak exposure (C(max) at steady state GMR, 0.88 [90% CI, 0.79-0.99]) when linagliptin was coadministered that was not considered clinically meaningful. No adverse events were reported during the coadministration period. No hypoglycemia was reported. Empagliflozin and linagliptin were well tolerated. CONCLUSION: These data support the coadministration of empagliflozin and linagliptin without dose adjustments. European Union Drug Regulating Authorities Clinical Trials Registration: EudraCT 2008-006089-27.