Label Changes About Side Effects For These Type 2 Diabetes Medicines In The Drug Class Called Dipeptidyl Peptidase-4 (DPP-4) Inhibitors
In August 2015 the FDA announced that it has found indications of a new side effect for a class of diabetes drugs -- dipeptidyl peptidase-4 (DPP-4) inhibitors -- that includes Januvia, Onglyza, Tradjenta, and Nesina.
The FDA found drug adverse event reports of arthralgia, or severe pain in one or more joints, associated with the use of DPP-4 inhibitor diabetes drugs, with Januvia being the one implicated most often, followed by Onglyza.
According to the FDA, patients started having symptoms of the new side effect from one day to years after they started taking Januvia, Onglyza, Tradjenta, Nesina or one of the "combination" DPP-4 inhibitors, e.g., Janumet (sitagliptin and metformin).
In more detail, the FDA reported that after the DPP-4 inhibitor medicine was discontinued, the patients' symptoms were usually relieved within less than a month of stopping the subject drug. Furthermore, some patients developed severe joint pain again when they restarted the same medicine or another DPP-4 inhibitor.
This last fact provides some substantiation for linking this severe joint pain side effect with Januvia, Onglyza, Tradjenta, Nesina, and the other drugs in this DPP-4 inhibitors class.
Januvia / Onglyza / Tradjenta / Nesina
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We get the following more detailed information from the "FDA Drug Safety Communication: FDA warns that DPP-4 inhibitors for type 2 diabetes may cause severe joint pain" document that was issued on August 28, 2015:
In a search of the FDA Adverse Event Reporting System (FAERS) database, we identified 33 cases of severe arthralgia reported with the use of dipeptidyl peptidase-4 (DPP-4) inhibitors from October 16, 2006, approval date of the first DPP-4 inhibitor, through December 31, 2013. Each case involved the use of one or more DPP-4 inhibitor. [Januvia (sitagliptin)] (n=28) was the most frequently reported, followed by [Onglyza (saxagliptin)] (n=5), [Tradjenta (linagliptin)] (n=2), [Nesina (alogliptin)] (n=1), and vildagliptin (n=2); vildagliptin is not marketed in the United States. In five cases, the patient experienced severe arthralgia with two different DPP-4 inhibitors. All 33 patients experienced arthralgia that resulted in a substantial reduction in their prior level of activity, including 10 patients who were hospitalized due to disabling joint pain. In 22 cases, symptoms appeared within 1 month of initiation of treatment with a DPP-4 inhibitor. In 20 of the 33 cases, the DPP-4 inhibitor was suspected as a possible cause of arthralgia and was discontinued within a month following the onset of symptoms. However, 8 of the remaining 13 cases reported a period of 44 days to 1 year between the onset of symptoms and discontinuation of the DPP-4 inhibitor. In 23 of the 33 cases, symptoms resolved less than 1 month after discontinuation of the drug.
Reports of eight of the 33 cases documented a positive rechallenge. In these eight cases, individuals discontinued treatment, experienced a resolution of symptoms, restarted therapy with a DPP-4 inhibitor (a different member of the class in six of the eight cases), experienced the reappearance of the arthralgia, and subsequently, experienced resolution of the symptoms when DPP-4 inhibitor therapy was again discontinued. Twenty-one of the 33 patients were treated for arthritis with drug therapies that included corticosteroids, nonsteroidal anti-inflammatory drugs, methotrexate, and immune-modulating drugs....
We also searched the medical literature and identified seven case reports, two of which were also identified in the FAERS database.... [footnotes omitted]
Due to this drug safety development, the FDA has mandated that the respective drug companies add a new Warning and Precaution about this risk to the drug labels of all medicines in this dipeptidyl peptidase-4 (DPP-4) inhibitors class.
Here is a list of those drugs, which was included in this August 2015 FDA Drug Safety Communication:
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
We will continue to monitor this emerging drug safety issue concerning reports of arthralgia, or severe pain in one or more joints, associated with the use of these newer diabetes drugs.