Omarigliptin is being developed as a potent, once-weekly, oral dipeptidyl peptidase-4 inhibitor for the treatment of type 2 diabetes. This double-blind, randomized, placebo-controlled study evaluated the effects of age, sex, and obesity on the pharmacokinetics of omarigliptin in healthy subjects. A single oral dose of omarigliptin 10 mg (n = 6/panel) or placebo (n = 2/panel) was administered in the fasted state to elderly nonobese men and women,young obese (30 ࣘ body mass index [BMI] ࣘ 35 kg/m 2 ) men and women, and young nonobese women of nonchildbearing potential. Plasma was collected at selected postdose times for evaluation of omarigliptin concentrations. Pharmacokinetic parameters were compared with historical data from a previously-conducted single-dose study in young, healthy, nonobese men. There were no clinically significant differences in omarigliptin AUC 0-Ý , the primary pharmacokinetic parameter for assessing efficacy and safety, based on age, sex, or BMI (pooled nonobese elderly versus pooled nonobese young, young nonobese female versus young nonobese male, and pooled young obese versus pooled young nonobese). There were no serious adverse events or hypoglycemic events attributable to omarigliptin administration. Demographic factors and BMI had no meaningful effect on omarigliptin pharmacokinetics, suggesting that dose adjustment based on age, sex, or obesity is not required.
Keywords demographic analysis, dipeptidyl peptidase-4 inhibitor, omarigliptin, pharmacokinetics, type 2 diabetes mellitusIncretin hormones, including glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP), are released by the intestine in response to a meal. These peptides lower blood glucose concentrations by stimulating glucose-dependent insulin secretion from β-cells. In addition, GLP-1 decreases glucagon levels reduces food intake, induces satiety, and delays gastric emptying.1 The effects of incretin hormones are short-lived (1-2 minutes) because they are rapidly degraded by the enzyme dipeptidyl peptidase-4 (DPP-4) in vivo.2-4 One therapeutic approach to mitigate this limitation is prolongation of the effects of GLP-1 and GIP by inhibition of DPP-4.