Clinical trials are conducted before a new drug is released for sale, in part to test for bad things that might happen when people take it. But clinical trials don’t involve all that many people: several thousand at the most. After the clinical trials are successfully completed, however, the drug is sold to millions upon millions. Merck’s sales of Januvia and Janumet, for example, totaled over a billion dollars in the first six months of this year alone.
Those millions of Januvia-takers constitute an informal “post-marketing” trial that involves a much larger population over a much longer time than formal clinical trials. For that reason, it can sometimes detect rare or long-term adverse effects that were not noted previously. Any adverse events that occur in people during post-marketing must be reported to the FDA. That’s how the FDA learned of the cases of pancreatitis in users of Byetta. And now it’s learned of the same phenomenon in users of Januvia (sitagliptin) and Janumet (sitagliptin plus metformin).
The FDA has just reported that sitagliptin has generated 88 post-marketing cases of acute pancreatitis in patients using sitagliptin, including two cases of hemorrhagic or necrotizing pancreatitis, between October 16, 2006, and February 9, 2009. Nineteen of the cases (21%) occurred within 30 days of starting sitagliptin or sitagliptin/metformin, and 47 of the cases (53%) resolved once sitagliptin was discontinued.
The FDA also noted that 45 of the pancreatitis cases (51 percent) were associated with at least one other risk factor for developing pancreatitis, such as diabetes, obesity, high cholesterol and/or high triglycerides. This fact is highly regarded by Merck, which issued a statement rebutting the conclusion that sitagliptin is associated with pancreatitis.
Merck noted that in clinical trials of up to two years long, with more than 6,000 patients, sitagliptin was not associated with an increase in the incidence of pancreatitis. And clinical studies, they believe, are what people should be paying attention to. They noted that because post-marketing events are reported voluntarily from a population of uncertain size, “it is generally not possible to reliably establish the frequency of such events or establish a causal relationship between a medicine and a specific adverse event.”
Merck added that there have been reports of pancreatitis following use of many other prescription and nonprescription medications, including other type 2 diabetes prescription medications. Like Byetta, to which the comment may be referring, sitagliptin acts on GLP-1. Januvia inhibits DPP-4, which breaks down GLP-1, and Byetta mimics natural GLP-1.
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