The U.S. Food and Drug Administration (FDA) has issued a new warning and precaution about the risks of severe and disabling joint pain related to the class of dipeptidyl peptidase-4 (DPP-4) inhibitors used to treat diabetes.1 Drugs in this class include alogliptin (Nesina), linagliptin (Tradjenta), saxagliptin (Onglyza) and sitagliptin (Januvia). All single-agent DPP-4 inhibitors and their combinations are subject to the warning. Combinations include sitagliptin/metformin and ER (Janumet/XR), saxagliptin/metformin ER (Kombiglyze XR), linagliptin/empagliflozin (Glyxambi), linaglitptin/metformin (Jentadueto), alogliptin/metformin (Kazano) and alogliptin/pioglitazone (Oseni).
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The onset of joint pain in patients taking these therapies can occur at any time during treatment, from one day to years after starting the drug therapy. Patients experienced symptom relief after discontinuing the medication. When re-challenged with a DPP-4 inhibitor, some patients had a recurrence of severe joint pain.
Healthcare professionals should consider DPP-4 inhibitors as a possible cause of severe and persistent joint pain in patients receiving these treatments if other causes are ruled out. Healthcare professionals are encouraged to report any suspected adverse drug reactions to the FDA’s MedWatch Program. Directions for the program’s Online Voluntary Reporting Form are available online, as well as more detailed information about the FDA Adverse Event Reporting System (FAERS).2–4
Additionally, the FDA has strengthened the warnings and precautions sections of the drug labels for the sodium-glucose cotransporter-2 (SGLT2) inhibitor canagliflozin (Invokana, Invokamet).5 This warning is related to an increased risk of bone fractures. The FDA added new information about decreases in bone mineral density seen with canagliflozin at both the hip and spine areas. Healthcare professionals should consider factors that contribute to fracture risk prior to starting patients on canagliflozin. Bone fractures have been seen in patients taking canagliflozin as early as 12 weeks after beginning treatment.
Michele B. Kaufman, PharmD, CGP, RPh, is a freelance medical writer based in New York City and a pharmacist at New York Presbyterian Lower Manhattan Hospital.
- U.S. Food and Drug Administration. FDA drug safety communication: FDA warns that DPP-4 inhibitors for type 2 diabetes may cause severe joint pain. 2015 Aug 25.
- U.S. Food and Drug Administration. MedWatch online voluntary reporting form. 2015.
- U.S. Food and Drug Administration. MedWatch voluntary report. 2015.
- U.S. Food and Drug Administration. FDA adverse event reporting system (FAERS). 2015.
- U.S. Food and Drug Administration. Invokana and Invokamet (canagliflozin): Drug safety communication—new information on bone fracture risk and decreased bone mineral density. 2015 Sep 10.