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One year ago, we reviewed the newly approved diabetes drug sitagliptin (JANUVIA) and classified it as Do Not Use Until 2014 because it did not represent a breakthrough for diabetes treatment, it is less effective than the older diabetes drug glipizide (GLUCOTROL) and clinical studies showed it could cause health risks and damage kidneys. We also stated that inadequate information about its safety was available.
Now, an increasing body of evidence documents the risks associated with...
One year ago, we reviewed the newly approved diabetes drug sitagliptin (JANUVIA) and classified it as Do Not Use Until 2014 because it did not represent a breakthrough for diabetes treatment, it is less effective than the older diabetes drug glipizide (GLUCOTROL) and clinical studies showed it could cause health risks and damage kidneys. We also stated that inadequate information about its safety was available.
Now, an increasing body of evidence documents the risks associated with sitagliptin, and several reviews have cautioned against its use. We are therefore re-categorizing the drug as Do Not Use, removing our previous proviso that it might be safe to use after 2014.
Our new warning is especially urgent because, due to massive promotion, this drug has quickly become one of the 100 top-selling drugs in the country, with 2.7 million prescriptions filled in 2007, totaling $472 million.
Since the drug was approved, the FDA has required that important new risk information be added to the drug’s label:
• “There have been postmarketing reports of serious allergic and hypersensitivity reactions in patients treated with JANUVIA such as anaphylaxis, angioedema, and exfoliative skin conditions including Stevens-Johnson syndrome [see box]. In such cases, promptly stop JANUVIA, assess for other potential causes, institute appropriate monitoring and treatment, and initiate alternative treatment for diabetes.”
• “Hypoglycemia [low blood sugar] was also reported more commonly in patients treated with the combination of JANUVIA and sulfonylurea [see table], with or without metformin, than in patients given the combination of placebo and sulfonylurea, with or without metformin.” Related to this, the following statement was also added: ’When used with a sulfonylurea , a lower dose of sulfonylurea may be required to reduce the risk of hypoglycemia.’”
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Stevens-Johnson syndrome is a condition caused by, among other things, individual drugs or drug interactions. Patients with Stevens-Johnson syndrome may experience skin cell necrosis, or skin cell death: portions of a layer of the skin called the epidermis dies and become separated from another layer called the dermis. Although the condition is potentially life-threatening, it is treatable if detected early enough, and death in these patients is extremely rare. |
Doubts raised
A lack of support for sitagliptin in the scientific community has been growing as major medical journals have published less-than-stellar reviews of the drug. For instance, La Revue Prescrire, a French publication for physicians and pharmacists, has taken a strong stance against the drug. In a February 2008 article, several reasons are given for this conclusion:
• “Sitagliptin has not been tested for its effect on morbidity or mortality endpoints.”
• “Sitagliptin induced a limited reduction in glycated haemoglobin levels [a measure of blood sugar control], which usually remained above the cutoff point (7 percent) generally used to define proper sugar control.”
• “In the short term, the main adverse effects of sitagliptin are nausea and constipation. In the long term, there is a risk of infections, especially upper respiratory tract infections … Sitagliptin sometimes increases creatinine levels [a measure of kidney function].”
The review concluded that “whether used alone or in combination, the antidiabetic effects of sitagliptin, so far studied on surrogate endpoints [measures of blood sugar control] are too modest, given the outstanding safety issues, to recommend its use in patients with type 2 diabetes.”
Two months later, in April 2008, the Cochrane Collaboration, which performs comprehensive reviews of drugs, analyzed the data on sitagliptin and published the following findings:
• “Since the new DPP-4 inhibitors [such as sitagliptin] may influence immune function additional long-term data on the safety of these drugs are necessary. Also, cardiovascular outcomes like heart attacks and strokes should not be increased with any antidiabetic therapy but data so far are lacking.”
• “All-cause infections (for example nasopharyngitis, upper respiratory tract infection, urinary tract infection) showed a statistically significant increase after sitagliptin treatment.
The Cochrane Collaboration concluded that “until new information arrives, DPP-4 inhibitors should only be used under controlled conditions and in individual patients.”
The earlier statement of the U.S. Medical Letter in January 2007 appears particularly prescient in light of these later conclusions:
The effectiveness of sitagliptin compared to older drugs and its long-term safety and efficacy remain to be established. Metformin and sulfonylureas (see table below) appear to be more effective in lowering HbA1c levels in the short term, and they cost much less.
Public Citizen agrees.
* Do Not Use in Worst Pills, Best Pills
** Limited Use in Worst Pills, Best Pills
