Pharmacokinetics and pharmacodynamic effects of the oral DPP-4 inhibitor sitagliptin in middle-aged obese subjects.

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Herman GA, Bergman A, Liu F, Stevens C, Wang AQ, Zeng W, Chen L, Snyder K, Hilliard D, Tanen M, Tanaka W, Meehan AG, Lasseter K, Dilzer S, Blum R, Wagner JA

Pharmacokinetics and pharmacodynamic effects of the oral DPP-4 inhibitor sitagliptin in middle-aged obese subjects.

J Clin Pharmacol. 2006 Aug;46(8):876-86.

PubMed ID

16855072 [ View in PubMed

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Abstract

Sitagliptin (MK-0431) is an oral, potent, and selective dipeptidyl peptidase-IV (DPP-4) inhibitor developed for the treatment of type 2 diabetes. This multicenter, randomized, double-blind, placebo-controlled study examined the pharmacokinetic and pharmacodynamic effects of sitagliptin in obese subjects. Middle-aged (45-63 years), nondiabetic, obese (body mass index: 30-40 kg/m2) men and women were randomized to sitagliptin 200 mg bid (n = 24) or placebo (n = 8) for 28 days. Steady-state plasma concentrations of sitagliptin were achieved within 2 days of starting treatment, and >90% of the dose was excreted unchanged in urine. Sitagliptin treatment led to approximately 90% inhibition of plasma DPP-4 activity, increased active glucagon-like peptide-1 (GLP-1) levels by 2.7-fold (P < .001), and decreased post-oral glucose tolerance test glucose excursion by 35% (P < .050) compared to placebo. In nondiabetic obese subjects, treatment with sitagliptin 200 mg bid was generally well tolerated without associated hypoglycemia and led to maximal inhibition of plasma DPP-4 activity, increased active GLP-1, and reduced glycemic excursion.

DrugBank Data that Cites this Article

Drugs

Sitagliptin

Drug Targets

Drug	Target	Kind	Organism	Pharmacological Action	Actions
Sitagliptin	Dipeptidyl peptidase 4	Protein	Humans	Yes	Inhibitor	Details