Initial combination therapy with sitagliptin, a dipeptidyl peptidase-4 inhibitor, and metformin for patients with Type 2 diabetes mellitus

Abstract

The two incretin hormones, glucagon-like peptide (GLP)-1 and glucose-dependent insulinotropic polypeptide potentiate nutrient-dependent insulin secretion following meal ingestion. Metabolic control can be improved markedly by administration of exogenous GLP-1, but the native peptide is almost immediately degraded by the enzyme dipeptidyl peptidase (DPP)-4 and, therefore, has little clinical value. Oral formulations that inhibit DPP-4, thereby prolonging the duration of endogenous incretin action, have, therefore, been developed. Sitagliptin, a once-daily, orally active, competitive and fully reversible inhibitor of DPP-4, was, as first in its class, introduced to the market as Januvia™. Recently, the US FDA approved initial combination therapy with sitagliptin and metformin (Janumet™) in order to help more patients with Type 2 diabetes mellitus get closer to accepted glycemic control targets, as recommended by standard guidelines. This article reviews initial treatment with Janumet as an alternative to monotherapy.

Keywords::

• dipeptidyl peptidase-4
• glucagon-like peptide-1
• glucose-dependent insulinotropic polypeptide
• incretin
• inhibitor
• sitagliptin
• Type 2 diabetes

Financial & competing interests disclosure

Tina Vilsbøll has worked as a consultant and received lecture fees from Novo Nordisk, Novartis, Merck, Sharp & Dohme and Lilly during the last years, as well as being on the Advisory Board for Merck Sharp & Dohme and Novartis. The author has no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.