Effect of Initial Combination Therapy With Sitagliptin, a Dipeptidyl Peptidase-4 Inhibitor, and Metformin on Glycemic Control in Patients With Type 2 Diabetes
- Barry J. Goldstein, MD1,
- Mark N. Feinglos, MD2,
- Jared K. Lunceford, PHD3,
- Jeremy Johnson, MD, BS3,
- Debora E. Williams-Herman, MD3 and
- for the Sitagliptin 036 Study Group*
- 1Division of Endocrinology, Diabetes, and Metabolic Diseases, Jefferson Medical College, Philadelphia, Pennsylvania
- 2Division of Endocrinology, Metabolism, and Nutrition, Duke University Medical Center, Durham, North Carolina
- 3Clinical and Quantitative Sciences, Merck Research Laboratories, Rahway, New Jersey
- Address correspondence and reprint requests to Debora Williams-Herman, MD, Merck Research Laboratories, RY34-A232, Rahway, NJ 07065. E-mail: debora_williamsherman{at}merck.com
Abstract
OBJECTIVE—To assess the efficacy and safety of initial combination therapy with sitagliptin and metformin in patients with type 2 diabetes and inadequate glycemic control on diet and exercise.
RESEARCH DESIGN AND METHODS—In a 24-week, randomized, double-blind, placebo-controlled, parallel-group study, 1,091 patients with type 2 diabetes and A1C 7.5–11% were randomized to one of six daily treatments: sitagliptin 100 mg/metformin 1,000 mg (S100/M1000 group), sitagliptin 100 mg/metformin 2,000 mg (S100/M2000 group), metformin 1,000 mg (M1000 group), metformin 2,000 mg (M2000 group) (all as divided doses administered twice daily [b.i.d.]), sitagliptin 100 mg q.d. (S100 group), or placebo. Patients who had an A1C >11% or a fasting glucose value >280 mg/dl after the run-in period were not eligible to be randomized; these patients could participate in an open-label substudy and were treated with S100/M2000 for 24 weeks.
RESULTS—The mean baseline A1C was 8.8% in the randomized patients. The placebo-subtracted A1C change from baseline was −2.07% (S100/M2000), −1.57% (S100/M1000), −1.30% (M2000), −0.99% (M1000), and −0.83% (S100) (P < 0.001 for comparisons versus placebo and for coadministration versus respective monotherapies). The proportion of patients achieving an A1C <7% and <6.5% was 66 and 44%, respectively, in the S100/M2000 group (P < 0.001 vs. S100 or M2000). For the open-label cohort (n = 117; baseline A1C 11.2%) treated with S100/M2000, the within-group mean A1C change from baseline was −2.9%. The incidence of hypoglycemia was low (0.5–2.2%) across active treatment groups and not significantly different from that in the placebo group (0.6%). The incidence of gastrointestinal adverse experiences was similar for coadministration therapies compared with their respective metformin monotherapy.
CONCLUSIONS—The initial combination of sitagliptin and metformin provided substantial and additive glycemic improvement and was generally well tolerated in patients with type 2 diabetes.
- APT, all patients treated
- AUC, area under the curve
- FPG, fasting plasma glucose
- GLP, glucagon-like peptide
- HOMA-β, homeostasis model assessment of β-cell function
- HOMA-IR, HOMA of insulin resistance
- OHA, oral antihyperglycemic agent
- PPG, postprandial plasma glucose
Footnotes
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Published ahead of print at http://care.diabetesjournals.org on 7 May 2007. DOI: 10.2337/dc07-0627. Clinical trial reg. no. NCT00103857, clinicaltrials.gov.
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↵* Members of the Sitagliptin 036 Study Group, as well as additional information, are listed in an online appendix available at http://dx.doi.org/10.2337/dc07-0627.
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B.J.G. has received honoraria and grant/research support from and has been a consultant for Merck. M.N.F. has served on an advisory board for Merck.
A table elsewhere in this issue shows conventional and Système International (SI) units and conversion factors for many substances.
The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked “advertisement” in accordance with 18 U.S.C Section 1734 solely to indicate this fact.
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- Accepted May 3, 2007.
- Received March 30, 2007.
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