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
Author:
Charbonnel Bernard1, Karasik Avraham2, Liu Ji3, Wu Mei3, Meininger Gary3,
Affiliation:
1. Centre Hospitalier Universitaire de Nantes, Nantes, France 2. Chaim Sheba Medical Center, Tel Hashomer, Israel 3. Merck Research Laboratories, Rahway, New Jersey
Abstract
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] ≥7 and ≤10%) with metformin alone.
RESEARCH DESIGN AND METHODS—After a screening diet/exercise run-in period, a metformin dose titration/stabilization period, and a 2-week, single-blind, placebo run-in period, 701 patients, aged 19–78 years, with mild to moderate hyperglycemia (mean A1C 8.0%) receiving ongoing metformin (≥1,500 mg/day) were randomly assigned to receive the addition of placebo or sitagliptin 100 mg once-daily in a 1:2 ratio for 24 weeks. 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 reductions 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 β-cell function, and quantitative 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 weight decreased similarly with sitagliptin and placebo.
CONCLUSIONS—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.
Publisher
American Diabetes Association
Subject
Advanced and Specialized Nursing,Endocrinology, Diabetes and Metabolism,Internal Medicine
Reference15 articles.
1. Kim D, Wang L, Beconi M, Eiermann GJ, Fisher MH, He H, Hickey GJ, Kowalchick JE, Leiting B, Lyons K, Marsilio F, McCann ME, Patel RA, Petrov A, Scapin G, Patel SB, Roy RS, Wu JK, Wyvratt MJ, Zhang BB, Zhu L, Thornberry NA, Weber AE: (2R)-4-Oxo-4-[3-(trifluoromethyl)-5,6-dihydro[1,2,4]triazolo[4,3-a]pyrazin-7(8H)-yl]-1-(2,4,5-trifluorophenyl)butan-2-amine: a potent, orally active dipeptidyl peptidase IV inhibitor for the treatment of type 2 diabetes. J Med Chem 48: 141–151, 2005 2. Herman GA, Stevens C, Van Dyck K, Bergman A, Yi B, DeSmet M, Snyder K, Hilliard D, Tanen M, Tanaka W, Wang AQ, Chen L, Zeng W, Musson D, Laethem M, Zhou YY, Winchell G, Davies MJ, Ramael S, Gottesdiener KM, Wagner JA: Pharmacokinetics and pharmacodynamics of single doses of sitagliptin, an inhibitor of dipeptidyl peptidase-IV, in healthy subjects. Clin Pharm Ther 78: 675–688, 2005 3. Herman GA, Bergman A, Stevens C, Kotey P, Yi B, Zhao P, Dietrich B, Golor G, Schrodter A, Keymeulen B, Lasseter KC, Kipnes MS, Snyder K, Hilliard D, Tanen M, Cilissen C, De Smet M, de Lepeleire I, Van Dyck K, Wang AQ, Zeng W, Davies MJ, Tanaka W, Holst JJ, Deacon CF, Gottesdiener KM, Wagner JA: Effect of single oral doses of sitagliptin, a dipeptidyl peptidase-4 inhibitor, on incretin and plasma glucose levels following an oral glucose tolerance test in patients with type 2 diabetes. J Clin Endocrinol Metab. 91: 4612−4619, 2006 4. Scott R, Herman GA, Zhao PL, Chen X, Wu M, Stein PP: Twelve-week efficacy and tolerability of MK-0431, a dipeptidyl peptidase IV (DPP-IV) inhibitor, in the treatment of type 2 diabetes (Abstract). Diabetes 54: A10, 2005 5. Herman GA, Hanefeld M, Wu M, Chen X, Zhao PL, Stein PP: Effect of MK-0431, dipeptidyl peptidase IV (DPP-IV) inhibitor, on glycemic control after 12 weeks in patients with type 2 diabetes (Abstract). Diabetes 54: A134, 2005
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