Sitagliptin inhibited plasma dipeptidyl peptidose-IV activity and increased glucagons-like peptide-1 in nondiabetic obese subjects.
“Sitagliptin (MK-0431) is an oral, potent, and selective dipeptidyl peptidose-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,” investigators in the United States report.
G.A. Herman and colleagues at Merck Research Laboratories explained, “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.”
The investigators discovered, “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 similar to 90% inhibition of plasma DPP-4 activity, increased active glucagon-like peptide-1 (GLP-1) levels by 2.7-fold (p<0.001), and decreased postoral glucose tolerance test glucose excursion by 35% (p<0.050) compared to placebo."
The researchers concluded, “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.”
Herman and colleagues published their study in the Journal of Clinical Pharmacology (Pharmacokinetics and pharmacodynamic effects of the oral DPP-4 inhibitor sitagliptin in middle-aged obese subjects. J Clin Pharmacol, 2006;46(8):876-886).
For additional information, contact G.A. Herman, Merck Research Laboratories, RY34-A536, 126 E Lincon Avenue, Rahway, NJ 07065, USA.
The publisher of the Journal of Clinical Pharmacology can be contacted at: Sage Publications Inc., 2455 Teller Rd., Thousand Oaks, CA 91320, USA.