Reference

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

All Rights Reserved. Pharmacokinetics and pharmacodynamic effects of the oral DPP-4 inhibitor sitagliptin in middle-aged obese subjects. Herman, Gary A.; Bergman, Arthur; Liu, Fang; Stevens, Cathy; Wang, Amy Q.; Zeng, Wei; Chen, Li; Snyder, Karen; Hilliard, Deborah; Tanen, Michael; Tanaka, Wesley; Meehan, Alan G.; Lasseter, Kenneth; Dilzer, Stacy; Blum, Robert; Wagner, John A. (Merck Research Laboratories, Rahway, NJ, USA). Journal of Clinical Pharmacology, 46(8), 876-886 (English) 2006 Sage Publications. CODEN: JCPCBR. ISSN: 0091-2700. DOCUMENT TYPE: Journal CA Section: 1 (Pharmacology) 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 examd. 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 concns. of sitagliptin were achieved within 2 days of starting treatment, and >90% of the dose was excreted unchanged in urine. Sitagliptin treatment led to ~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 non-diabetic obese subjects, treatment with sitagliptin 200 mg bid was generally well tolerated without assocd. hypoglycemia and led to maximal inhibition of plasma DPP-4 activity, increased active GLP-1, and reduced glycemic excursion.Except for chemicals metioned above, 486460-32-6 and 89750-14-1 are also used. .

Efficacy and safety of the dipeptidyl peptidase-4 inhibitor sitagliptin added to ongoing metformin therapy in patients with type 2 diabetes inadequately controlled with metformin alone

All Rights Reserved. Efficacy and safety of the dipeptidyl peptidase-4 inhibitor sitagliptin added to ongoing metformin therapy in patients with type 2 diabetes inadequately controlled with metformin alone. Charbonnel, Bernard; Karasik, Avraham; Liu, Ji; Wu, Mei; Meininger, Gary (SITAGLIPTIN STUDY 020 GROUP; Centre Hospitalier Universitaire de Nantes, Nantes, Fr.). Diabetes Care, 29(12), 2638-2643 (English) 2006 American Diabetes Association, Inc. 9035-68-1 and 486460-32-6 are also occured in this study. CODEN: DICAD2. ISSN: 0149-5992. DOCUMENT TYPE: Journal CA Section: 1 (Pharmacology) OBJECTIVE: The efficacy and safety of the dipeptidyl peptidase-4 inhibitor, sitagliptin, added to ongoing metformin therapy, were assessed in patients with type 2 diabetes who had inadequate glycemic control (HbA1c [A1C] 37 and ￡10%) with metformin alone. RESEARCH DESIGN AND METHODS: After a screening diet/exercise run-in period, a metformin dose titrn./stabilization period, and a 2-wk, single-blind, placebo run-in period, 701 patients, aged 19-78 years, with mild to moderate hyperglycemia (mean A1C 8.0%) receiving ongoing metformin (31,500 mg/day) were randomly assigned to receive the addn. of placebo or sitagliptin 100 mg once-daily in a 1:2 ratio for 24 wk. Patients exceeding specific glycemic limits were provided rescue therapy (pioglitazone) until the end of the study. The efficacy analyses were based on an all-patients-treated population using an ANCOVA and excluded data obtained after glycemic rescue. RESULTS: At week 24, sitagliptin treatment led to significant redns. compared with placebo in A1C (-0.65%), fasting plasma glucose, and 2-h postmeal glucose. Fasting insulin, fasting C-peptide, fasting proinsulin-to-insulin ratio, postmeal insulin and C-peptide areas under the curve (AUCs), postmeal insulin AUC-to-glucose AUC ratio, homeostasis model assessment of b-cell function, and quant. insulin sensitivity check index were significantly improved with sitagliptin relative to placebo. A significantly greater proportion of patients achieved an A1C <7% with sitagliptin (47.0%) than with placebo (18.3%). There was no increased risk of hypoglycemia or gastrointestinal adverse experiences with sitagliptin compared with placebo. Body wt. decreased similarly with sitagliptin and placebo. CONCLUSION: Sitagliptin 100 mg once-daily added to ongoing metformin therapy was efficacious and well tolerated in patients with type 2 diabetes who had inadequate glycemic control with metformin alone. .