| Reference | 1. Diabetes Care. 2015 Nov;38(11):2106-14. doi: 10.2337/dc15-0109. Epub 2015 Aug 26.
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Safety and Efficacy of Omarigliptin (MK-3102), a Novel Once-Weekly DPP-4
Inhibitor for the Treatment of Patients With Type 2 Diabetes.
<br>
Sheu WH(1), Gantz I(2), Chen M(3), Suryawanshi S(3), Mirza A(3), Goldstein BJ(3),
Kaufman KD(3), Engel SS(3).
<br>
Author information: <br>
(1)Division of Endocrinology and Metabolism, Department of Internal Medicine,
Taichung Veterans General Hospital, Taichung, Taiwan; School of Medicine,
National Yang-Ming University, Taipei, Taiwan; and College of Medicine, National
Defense Medical Center, Taipei, Taiwan.
(2)Merck & Co., Inc., Kenilworth, NJ [email protected].
(3)Merck & Co., Inc., Kenilworth, NJ.
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OBJECTIVE: This study was conducted to determine the optimal dose of
omarigliptin, a once-weekly (q.w.) dipeptidyl peptidase IV (DPP-4) inhibitor, for
the treatment of patients with type 2 diabetes and evaluate the long-term safety
of that dose.<br>
RESEARCH DESIGN AND METHODS: In a multicenter, double-blind, 12-week, dose-range
finding study, 685 oral antihyperglycemic agent-naïve or washed-out subjects with
type 2 diabetes were randomized to one of five once-weekly doses of omarigliptin
(0.25 mg, 1 mg, 3 mg, 10 mg, or 25 mg) or placebo. The primary efficacy end point
was change from baseline in HbA1c, and secondary end points were 2-h postmeal
glucose (PMG) and fasting plasma glucose (FPG). Analysis included all patients
who received at least one dose of the study medication. Subjects who completed
the base study were eligible to enter a 66-week extension study.
RESULTS: Once-weekly treatment for 12 weeks with omarigliptin provided
dose-related reductions in HbA1c, 2-h PMG, and FPG. At week 12, the omarigliptin
25-mg dose provided the greatest glycemic efficacy. The placebo-adjusted
least-squares mean reductions from baseline in HbA1c, 2-h PMG, and FPG were
-0.72% (-7.8 mmol/mol), -2.5, and -1.3 mmol/L, respectively (all P < 0.001). The
incidence of adverse events was similar across dose groups, with a low incidence
of symptomatic hypoglycemia and no effect on body weight. Omarigliptin was
generally well-tolerated throughout the base and extension studies.
CONCLUSIONS: Omarigliptin 25 mg q.w., compared with placebo, provided significant
glucose lowering and was generally well tolerated for up to 78 weeks in patients
with type 2 diabetes.
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2. J Med Chem. 2014 Apr 24;57(8):3205-12. doi: 10.1021/jm401992e. Epub 2014 Apr 2.
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Omarigliptin (MK-3102): a novel long-acting DPP-4 inhibitor for once-weekly
treatment of type 2 diabetes.
<br>
Biftu T(1), Sinha-Roy R, Chen P, Qian X, Feng D, Kuethe JT, Scapin G, Gao YD, Yan
Y, Krueger D, Bak A, Eiermann G, He J, Cox J, Hicks J, Lyons K, He H, Salituro G,
Tong S, Patel S, Doss G, Petrov A, Wu J, Xu SS, Sewall C, Zhang X, Zhang B,
Thornberry NA, Weber AE.
<br>
Author information: <br>
(1)Department of Discovery Chemistry, ‡Department of Metabolic Disorders,
§Department of Pharmacology, ∥Department of Drug Metabolism, ⊥Basic
Pharmaceutical Sciences, and #Department of Safety Assessment and Animal
Resources, Merck & Co., Inc. , Whitehouse Station, New Jersey 08889, United
States.
<br>
In our effort to discover DPP-4 inhibitors with added benefits over currently
commercially available DPP-4 inhibitors, MK-3102 (omarigliptin), was identified
as a potent and selective dipeptidyl peptidase 4 (DPP-4) inhibitor with an
excellent pharmacokinetic profile amenable for once-weekly human dosing and
selected as a clinical development candidate. This manuscript summarizes the
mechanism of action, scientific rationale, medicinal chemistry, pharmacokinetic
properties, and human efficacy data for omarigliptin, which is currently in phase
3 clinical development.
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