The first DPP-IV inhibitor, Januvia (sitagliptin, Merck), was approved in 2006 for use in type 2 adults. It is a once-daily drug that helps to stimulate insulin production while suppressing glucagon production by the pancreas, thereby decreasing the amount of glucose in the body.

Januvia does not cause weight gain and is not associated with hypoglycemia when used alone. And unlike some other oral medications, the drug has a very low incidence of gastrointestinal side effects (e.g., nausea, vomiting, diarrhea).

How They Work

Dipeptidyl peptidase-IV (DPP-IV) is a naturally occuring enzyme that breaks down incretins, which are hormones generated during the digestive process. Incretins bind to beta cell receptors on the pancreas, stimulating the release of insulin. The incretin known as glucagon-like peptide-1 (or GLP-1) also helps to suppress the production of glucagon by the pancreas (and subsequent glucose release by the liver), but after GLP-1 is released by the gut, it only lasts about two minutes in the human body before it is broken down by DPP-IV.

Drugs in the DPP-IV inhibitor class block the action of the DPP-IV enzyme, which helps these important incretins regulate blood glucose levels by increasing insulin production and lowering glucagon output.

Side Effects

The most commonly reported side effect of Januvia is headache and nasopharyngitis, or inflammation of the nasal passages. When Januvia is taken with pioglitizone, the most commonly reported side effect is upper respiratory tract infection.

Because Januvia is a relatively new medication and DPP-IV is a new drug class, further long-term research and follow-up studies are needed to determine the full range of potential side effects and risks associated with this drug.