Omarigliptin (MK-3102): A Comprehensive Pharmacological and Clinical Monograph

Executive Summary

Omarigliptin, known by its developmental code MK-3102, is a potent and highly selective small molecule inhibitor of the dipeptidyl peptidase-4 (DPP-4) enzyme. Developed by Merck & Co., it was engineered as a long-acting oral agent for the management of Type 2 Diabetes Mellitus (T2DM), distinguished within its class by a pharmacokinetic profile amenable to a once-weekly dosing regimen. This feature was designed to enhance patient convenience and medication adherence, addressing a significant challenge in the management of chronic diseases.

The mechanism of action of omarigliptin is consistent with other DPP-4 inhibitors, or "gliptins." By competitively and reversibly inhibiting the DPP-4 enzyme, it prevents the rapid degradation of endogenous incretin hormones, primarily glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP). The resulting increase in active incretin levels enhances glucose-dependent insulin secretion from pancreatic β-cells and suppresses glucagon release from α-cells, leading to improved glycemic control with a low intrinsic risk of hypoglycemia.

An extensive global clinical development program, O-QWEST, involving approximately 8,000 patients, demonstrated the robust efficacy and favorable safety profile of omarigliptin. In pivotal Phase 3 trials, once-weekly omarigliptin (25 mg) was proven to be non-inferior to the once-daily market leader, sitagliptin, in reducing glycosylated hemoglobin (HbA1c) levels. The drug was generally well-tolerated, with a safety profile comparable to both placebo and active comparators, and exhibited a weight-neutral effect.