On August 28, the US Food and Drug Administration (FDA) published a warning that a class of medications for type 2 diabetes, dipeptidyl peptidase-4 (DPP-4) inhibitors, may cause sever joint pain. The agency now requires that a new Warning and Precaution about this risk should be placed on all medicines in this drug class, which include sitagliptin, saxagliptin, linagliptin, and alogliptin.
The agency cautioned that patients should not stop taking their DPP-4 inhibitor medicine, but should contact their healthcare professional right immediately they experience severe and persistent joint pain. Thus, healthcare professionals should consider DPP-4 inhibitors as a possible cause of severe joint pain and discontinue the drug if appropriate. DPP-4 inhibitors are prescribed together 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 cardiovascular disease. These medicines are available as single-ingredient products and in combination with other diabetes medicines such as metformin.
The FDA conducted a s search of the FDA Adverse Event Reporting System (FAERS) database and the medical literature. The search yielded cases of severe joint pain associated with the use of DPP-4 inhibitors. Symptoms began from one day to years after they began taking a DPP-4 inhibitor. After the patients discontinued the DPP-4 inhibitor medicine, their symptoms resolved, usually in less than a month. Some patients developed severe joint pain again when they restarted the same medicine or another DPP-4 inhibitor.
The agency requests that healthcare professionals and patients should report side effects involving DPP-4 inhibitors to the FDA MedWatch program. A reporting form is available online at this link, or call 1-800-332-1088 to request a reporting form, then complete and return to the address on the pre-addressed form, or submit by fax to 1-800-FDA-0178.
The following medications contain DPP-4 inhibitors:
Janumet (sitagliptin and metformin)
Janumet XR (sitagliptin and metformin extended release)
Kombiglyze XR (saxagliptin and metformin extended release)
Glyxambi (linagliptin and empagliflozin)
Jentadueto (linagliptin and metformin)
Kazano (alogliptin and metformin)
Oseni (alogliptin and pioglitazone)