The FDA has added a new Warning and Precaution about this risk to the labels of all medicines in this drug class, called dipeptidyl peptidase-4 (DPP-4) inhibitors.
Patients should not stop taking their DPP-4 inhibitor medicine, but should contact their health care professional 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 type 2 diabetes. When untreated, type 2 diabetes can lead to serious problems, including blindness, nerve and kidney damage, and heart disease. These medicines are available as single-ingredient products and in combination with other diabetes medicines such as metformin (see Table 1 below).
In a search of the FDA Adverse Event Reporting System (FAERS) database and the medical literature,1-4 we 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 medicine, their symptoms were relieved, usually in less than a month. Some patients developed severe joint pain again when they restarted the same medicine or another DPP-4 inhibitor.
We urge health care professionals and patients to report side effects involving DPP-4 inhibitors to the FDA MedWatch program.
List of FDA-approved DPP-4 inhibitors
- Januvia (sitagliptin)
- Janumet (sitagliptin and metformin)
- Janumet XR (sitagliptin and metformin extended release)
- Onglyza (saxagliptin)
- Kombiglyze XR (saxagliptin and metformin extended release)
- Tradjenta (linagliptin)
- Glyxambi (linagliptin and empagliflozin)
- Jentadueto (linagliptin and metformin)
- Nesina (alogliptin)
- Kazano (alogliptin and metformin)
- Oseni (alogliptin and pioglitazone)