FDA issues gliptin joint pain warning
pharmafile | September 1, 2015 | News story | Manufacturing and Production | DPP-4 inhibitors, ESC, FDA, TECOS, adverse effects, drug safety, gliptins, safety alert, safety warning
The FDA has issued a safety alert, warning of joint pain caused by the gliptins, a common class of drugs for treatment type 2 diabetes.
The Agency’s drug safety team released a safety alerts for the gliptins, also known as the dipeptidyl peptidase-4 (DPP-4) inhibitors. The warning covers the entire class of drugs.
This includes: Merck’s Januvia (sitagliptin) and Janumet (sitagliptin and metformin), AstraZeneca’s Onglyza (saxagliptin) and its metformin combination drug Kombiglyze, Eli Lilly and Boehringer Ingelheim’s Tradjenta (linagliptin) and Glyxambi (empagliflozin and linagliptin) and Jentadueto (linagliptin and metformin), and Takeda’s Nesina (alogliptin), Kazano (alogliptin and metformin) and Oseni (alogliptin and pioglitazone).
The warnings have come about after a search of the FDA Adverse Event Reporting System database and medical journals revealed cases of severe joint pain in patients prescribed these treatments. Of the 33 reports of severe joint pain, 28 occured in Januvia and Janumet patients, the FDA says, with Onglyza accounting for five, Tradjenta two and Nesina one. Some patients took more than one DPP-4 drug over the course of their treatment.
As a result the FDA has added a new warning and precaution about the risk to the labels of all medicines in this drug class. The regulator advises that “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.”
Many industry observers consider this class of drugs to be under threat from the challenge posed by Boehringer Ingelheim and Lilly’s sodium glucose co-transporter type 2 (SGLT-2) inhibitor Jardiance (empagliflozin). Recent clinical trial results found Jardiance is the first diabetes drug to show it can reduce the risk of heart attacks, strokes and cardiovascular deaths.
This class of drug already features FDA safety warnings about their risk of pancreatitis and allergic reactions, as well as low blood sugar (hypoglycaemia) when used in combination with other diabetes drugs. An FDA advisory committee has said that the labels of Takeda’s Nesina and AstraZeneca’s Onglyza should carry a warning of the risk of heart problems.
However, a study presented at the European Society of Cardiology congress in London, a new sub-analysis of Merck’s TECOS study confirmed that Januvia appears to have a positive safety profile in patients with a prior history of heart failure.
The previous analysis looked at the long-term cardiovascular safety of adding Januvia to usual care in more than 14,000 patients with type 2 diabetes and established cardiovascular disease, and found no difference in the rates of hospitalisation for heart failure.
But these results were adjusted to control for baseline heart failure, which, “although this was a pre-specified endpoint, left some questions unanswered,” says Dr Darren McGuire, the lead researcher from University of Texas Southwestern Medical Center, in Dallas, Texas.
“Now we present unadjusted analyses (also pre-specified) with identical results, and we complement these with mulitivariable analyses – all yielding the identical conclusion: no signal of any sort for heart failure risk with sitagliptin. The stability of these findings across a very extensive set of complementary/sensitivity analyses is completely reassuring, both scientifically and for patients and providers, that no matter how we sliced and diced the data the same result was observed” he adds.
Lilian Anekwe
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