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FDA Warns That DPP-4 Inhibitors for Type-2 Diabetes May Cause Severe Joint Pain

New ‘warning and precautions’ section added to labels

The FDA is warning that the type-2 diabetes (T2D) drugs sitagliptin, saxagliptin, linagliptin, and alogliptin may cause joint pain that can be severe and disabling. The agency has added a new “warning and precaution” section about this risk to the labels of all medications in this drug class, called dipeptidyl peptidase-4 (DPP-4) inhibitors.

Patients should not stop taking their DPP-4 inhibitor medications, but should contact their health care professionals right away if they experience severe and persistent joint pain. Health care professionals should consider DPP-4 inhibitors as a possible cause of severe joint pain and discontinue the drug if appropriate.

DPP-4 inhibitors are used along with diet and exercise to lower blood sugar in adults with T2D. When untreated, T2D can lead to serious problems, including blindness, nerve and kidney damage, and heart disease. These medications are available as single-ingredient products and in combination with other diabetes drugs, such as metformin.

In a search of the FDA Adverse Event Reporting System (FAERS) database and the medical literature, the agency identified cases of severe joint pain associated with the use of DPP-4 inhibitors. Patients started having symptoms from 1 day to years after they started taking a DPP-4 inhibitor. After the patients discontinued the DPP-4 inhibitor medication, their symptoms were relieved, usually in less than a month. Some patients developed severe joint pain again when they restarted the same medication or another DPP-4 inhibitor.

The following DPP-4 inhibitors have been approved by the FDA:


  • Glyxambi (linagliptin and empagliflozin)

  • Janumet (sitagliptin and metformin)

  • Janumet XR (sitagliptin and metformin extended release)

  • Januvia (sitagliptin)

  • Jentadueto (linagliptin and metformin)

  • Kazano (alogliptin and metformin)

  • Kombiglyze XR (saxagliptin and metformin extended release)

  • Nesina (alogliptin)

  • Onglyza (saxagliptin)

  • Oseni (alogliptin and pioglitazone)

  • Tradjenta (linagliptin)

Source: FDA; August 28, 2015.

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