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DPP-4 Inhibitors

by Mark T. Marino, MD

Sitagliptin results in a low incidence of hypoglycemia, comparable to that of placebo, when tested as a stand-alone therapy. It is associated with a somewhat higher rate of hypoglycemia when used in combination with other drugs, especially with a sulfonylurea such as glipizide or glimepiride.

As mentioned earlier, DPP-4 was discovered through its association with the immune system, and some researchers thought that inhibiting it might impair the immune system. So far, data from clinical studies have not demonstrated a serious immunosuppresive effect. They do indicate, though, that sitagliptin increases the risk of upper respiratory infections and nasopharyngitis (inflammation of the nose and pharynx), found in 6.3% and 5.2% of study subjects, respectively, who took sitagliptin versus 3.3% and 3.4% for placebo.

The most worrying side effects are those reported since the drug came onto the market. These reactions seem to be allergic in nature and include anaphylaxis, a bodywide reaction that results in low blood pressure, and angioedema, a swelling of the tongue, face, and throat. Both of these may be life-threatening. The reactions have occurred anytime from immediately after taking the first dose until three months after starting the drug. There have also been reports of skin reactions, including a very severe type of drug reaction called Stevens–Johnson syndrome. Other diabetes drugs are not typically associated with Stevens–Johnson syndrome.

One more choice
DPP-4 inhibitors may be a useful addition to the treatment options for Type 2 diabetes. While the current DPP-4 inhibitors do not seem to have major, clearcut advantages over other therapies, they may be a reasonable alternative for people who cannot take certain other drugs. They may also be used with metformin when blood glucose control is not ideal. Whether these drugs could be used to preserve or improve pancreatic beta-cell function, as well, will be determined through further clinical trials. As options for treating Type 2 diabetes expand, new drugs, including DPP-4 inhibitors, help make it possible for more people to follow an effective, individualized plan for their diabetes.

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