Background:

Dipeptidyl peptidase IV (DPP-4) inhibitors improve glycemic control in patients with type 2 diabetes by prolonging the half-life of incretin peptides, which stimulate insulin secretion and decrease glucagon release in a glucose-dependent manner. MK-3102 is a novel long-acting DPP-4 inhibitor.

In vitro: MK-3102 is a competitive, reversible inhibitor of DPP-4 and is more potent than sitagliptin. It is highly selective over all proteases tested, including QPP, FAP, PEP, DPP8, and DPP9. The compound has weak ion channel activity [1].

In vivo: MK-3102 was evaluated for its ability to improve glucose tolerance in lean mice. When orally administered 1 h prior to dextrose challenge in an oral glucose tolerance test, it significantly reduced blood glucose excursion in a dosedependent manner from 0.01 mg/kg to 0.3 mg/kg [1].

Clinical trial: MK-3102 is currently in phase 3 clinical trial for type 2 diabetes mellitus. Dose-dependent efficacy in 2 h post meal glucose reduction, fasting plasma glucose reduction, and HbA1c and safety profile similar to that seen with once daily DPP-4 inhibitor such as sitagliptin was observed in a 12-week phase IIB dose-rangefinding study [1].

Reference:
[1] Biftu T, 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.  Omarigliptin (MK-3102): a novel long-acting DPP-4 inhibitor for once-weekly treatment of type 2 diabetes. J Med Chem. 2014 Apr 24;57(8):3205-12.