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Am Fam Physician. 2009;79(5):372

Author disclosure: Nothing to disclose.

Clinical Question

Are dipeptidyl-peptidase-4 (DPP-4) inhibitors safe and effective for the treatment of type 2 diabetes?

Evidence-Based Answer

When used as monotherapy or in conjunction with metformin (Glucophage) or thiazolidinediones, the DPP-4 inhibitor sitagliptin (Januvia) decreases A1C levels by 0.7 percent, but there are no data on patient-oriented outcomes or long-term safety. Until more studies are completed, it should only be used in individual patients when there are reasons that other better-studied agents are not sufficient.

Practice Pointers

Sitagliptin is in the class of drugs called DPP-4 inhibitors, and it is the first one available in the United States. Lower doses are required for patients with moderate and severe renal impairment. It slows the inactivation of incretin hormones, which increases their release from the intestine and prolongs their action. This increases the release of insulin and decreases glucagon. Sitagliptin has been studied as a monotherapy and in conjunction with metformin and thiazolidinediones.1 In conjunction with diet and exercise, 100 mg daily of sitagliptin is indicated to improve glycemic control in adults with type 2 diabetes.

In this Cochrane Review, the authors searched for randomized controlled trials of DPP-4 inhibitors in patients with type 2 diabetes. They found 11 trials comparing sitagliptin with placebo. The trials included a total of 6,743 patients, and followed patients from 12 to 52 weeks. Compared with placebo, sitagliptin reduced A1C levels by approximately 0.7 percent. They did not find any trials reporting patient-oriented outcomes (e.g., mortality, cardiovascular outcomes, diabetic complications, costs of treatment, health-related quality of life). Compared with sitagliptin, patients taking placebo had more weight loss, but the medication was not associated with weight gain. There were no episodes of severe hypoglycemia. All types of infections were increased for patients taking sitagliptin.

The treatment algorithm from the American Diabetes Association consensus guidelines does not include DPP-4 inhibitors because, like pramlintide (Symlin), exenatide (Byetta), alpha-glucosidase inhibitors, and meglitinides (i.e., nateglinide [Starlix] and repaglinide [Prandin]), they do not lower glucose levels as well as other agents, have limited clinical data, and are relatively expensive. Long-term effects on immune function and other adverse effects should be studied before sitagliptin is chosen over better-studied alternatives.2 However, it may be tried for some patients when other agents are not appropriate.

These are summaries of reviews from the Cochrane Library.

This series is coordinated by Corey D. Fogleman, MD, assistant medical editor.

A collection of Cochrane for Clinicians published in AFP is available at

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