Abstract
Purpose:
Linagliptin is an oral antihyperglycemic drug that acts by inhibiting the dipeptidyl
peptidase-4 enzyme. A 5-mg once-daily regimen is available, but an alternative regimen
was needed for twice-daily fixed-dose combinations. Although linagliptin has non-linear
pharmacokinetics, simulation suggested 2.5 mg twice-daily would provide bioequivalent
exposure and comparable plasma dipeptidyl peptidase-4 inhibition to 5 mg once-daily.
Methods:
This crossover study compared steady-state pharmacokinetics and pharmacodynamics of
linagliptin 5 mg once-daily and 2.5 mg twice-daily, both administered for 7 days.
Results:
In total, 16 healthy volunteers entered the study, and 15 completed both treatment
periods. Exposure over 24-h at steady state (AUC0–24,ss) was similar for linagliptin 5 mg once-daily and 2.5 mg twice-daily (132 vs. 124 nmol · h/L),
and the 90% confidence interval of the adjusted geometric mean ratio of AUC0–24,ss was well within the acceptance range for bioequivalence (ratio 93.9%; 90% confidence
interval 89.5, 98.5). Median dipeptidyl peptidase-4 inhibition over a 24-h interval
at steady state was 85.9% with linagliptin 5 mg once-daily and 86.5% with 2.5 mg twice-daily,
and median dipeptidyl peptidase-4 inhibition values were approximately 80.0% at trough.
Most subjects had no adverse events and there were no serious adverse events.
Conclusions:
Linagliptin 5 mg once-daily and 2.5 mg twice-daily provided bioequivalent exposure
and similar inhibition of dipeptidyl peptidase-4 over the whole dosing interval.
Key words
linagliptin - metformin - diabetes - fixed-dose combination - pharmacokinetics - pharmacodynamics
