Safety and tolerability of sitagliptin
Original source: BMC Endocrine Disorders 2008, 8:14
Authors: Debora Williams-Herman, Elizabeth Round, Arlene S. Swern, Bret Musser, Michael J. Davies, Peter P. Stein, Keith D. Kaufman and John M. Amatruda
Publication date: 27 October 2008
DOI (digital document ID): 10.1186/1472-6823-8-14
Requires subscription? No
Publicly-available abstract: Yes
Synopsis:
The authors are trying to assess the safety and of sitagliptin (Januvia) by combining the results of 12 separate double-blind human trials of up to 2 years in duration. (Double-blind trials are ones in which neither the investigators nor the patients know who is getting the drug under test and who is getting an alternate therapy or no drug therapy. This helps keep the results unbiased.)
A total of 6139 patients were involved in the studies; 3415 were either given 100 mg Januvia per day or the equivalent dose of another oral anti-diabetic pill; 2724 were given a placebo (a pill that has no drug action to it). The shortest study ran 18 weeks (about 4 months) and the longest ran 2 years. The patients were either given sitagliptin (Januvia) alone, or with metformin (similar to Janumet), or as addition to other antidiabetic drugs such as metformin (Glucophage), sulfonylurea, pioglitazone (Actos), and/or rosiglitazone (Avandia). The patients not getting the Januvia were getting either a placebo or one or more of the above antidiabetic drugs.
A number of known adverse reactions and side effects were examined in both the sitagliptin groups and the various control groups. According to the abstract, the only significant side effect was an increase in patient-reported hypoglycemic events among those patients who were also taking sulfonylurea drugs. The definition of "hypoglycemia" was somewhat loose, not requiring the patient to test his blood glucose and add it to the report. The authors do examine the frequency of reports of nausea and stomach pain, pancreatitis, immune system suppression, nose and throat discomfort, skin reactions (hives, discoloration, redness, etc.), and swelling in the heart and chest. These adverse reactions were considered to be similar in frequency between those taking Januvia and those who were not. The reasons for other studies reporting different results were discussed and discounted. (In at least one case, it was one of the longer-term studies that was looking specifically for adverse effects.)
The authors conclude that Under most circumstances, sitagliptin is safe and effective compared to other oral antidiabetic medications.
Reliability: The research was published in a peer-reviewed journal. One of the authors is a medical doctor.
All of the authors work for Merck, or worked for Merck during the period the research was being done. Merck manufactures Januvia, so the authors have a bias towards proving this medication safe and effective.
While a large number of patient experiences were collated into this analysis, most of the component studies were very small in scale.
Since most of the studies aggregated in this analysis only went on for four to six months, it is easy to misinterpret the data as indicating the drug is as safe over two years as it is over four months. People taking drugs to manage Type 2 diabetes are likely to stay on the same drug for much longer than the two-year longest studies examined -- so there is a possibility that there will be side effects from long-term use that have not yet shown up in laboratory and clinical studies.
Practical Applications:
Based on the authors' analysis, Januvia -- for the short-term and intermediate term -- is as safe as other drugs used to manage Type 2 diabetes.
However, because the severe reactions and deaths that have been tied to other new drugs* didn't start showing up in the media until the drugs were out in the marketplace for more than five years, and being taken by tens of thousands of patients, it is probably premature to say that Januvia is safe to be taken by the everyone covered by the prescribing instructions for the entire length of time one might expect it to be used. As with any medication, discuss the pros and cons with your doctor, as well as any additional concerns and risk factors you might have. Untreated Type 2 diabetes can cause serious complications up to and including death.
*Avandia (rosiglitazone), made by Glaxo Smith Kline, is the most recent drug with this sort of safety issue.
For further reading:
Januvia prescription information for doctors: http://www.merck.com/product/usa/pi_circulars/j/januvia/januvia_pi.pdf
Januvia site for consumers: http://www.januvia.com/sitagliptin/januvia/consumer/index.jsp
Merck website: http://www.merck.com/
Drugs.com consumer information for Januvia: http://www.drugs.com/cdi/januvia.html
Drugs.com professional information for Januvia: http://www.drugs.com/pro/januvia.html
This synopsis was based on the provisional (online preprint) article.
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