Safety profiles of JANUVIA and JANUMET drugs established through clinical development program

Sep 28 2009

Merck & Co., Inc., issued the following statement today in response to the U.S. Food and Drug Administration's (FDA's) update on JANUVIA (sitagliptin) and JANUMET (sitagliptin/metformin).

"Merck has thoroughly reviewed the safety data for sitagliptin, and sitagliptin was not associated with an increase in the incidence of pancreatitis in preclinical studies or in clinical trials of up to two years in duration with more than 6,000 patients. Merck has also carefully reviewed post marketing adverse experience reports, and Merck believes these data do not demonstrate that a causal relationship exists between sitagliptin and pancreatitis. Merck appreciates the important role that the FDA plays in assessing the safety of medicines and, as we do with all of our medicines, we will continue to monitor the safety of JANUVIA and will share the data with regulatory agencies and the medical community," said John Amatruda, M.D., Senior Vice President and Franchise Head, Diabetes and Obesity, Merck Research Laboratories. "Patients with type 2 diabetes are more likely to develop pancreatitis than other people, and as FDA noted in a publication earlier this year, 'diagnosis [of drug-induced pancreatitis] poses a challenge since it can be difficult to rule out other causes.' Merck would encourage any patient with concerns to speak with their physician."

There have been reports of pancreatitis following use of many other prescription medications and non-prescription medications, including other type 2 diabetes prescription medications.

JANUVIA is indicated, as an adjunct to diet and exercise, to improve glycemic control in adult patients with type 2 diabetes. JANUMET is indicated as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus when treatment with both sitagliptin and metformin is appropriate. JANUMET and JANUVIA should not be used in patients with type 1 diabetes or for the treatment of diabetic ketoacidosis. JANUMET and JANUVIA have not been studied in combination with insulin.

Merck carefully monitors post marketing reports for all of our medicines, including JANUVIA and JANUMET, and updates the label as appropriate. Post-marketing events are reported voluntarily from a population of uncertain size, and 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 has carefully reviewed the reports of pancreatitis in the post-marketing database, including the reports of more serious cases. In our review, the reports showed that the more serious cases also had other serious medical conditions. As is often the case with post-marketing reports, any causal association between sitagliptin and pancreatitis is difficult to assess due to such factors as the incompleteness of the reports and other serious concurrent conditions in some of the patients. Based on a qualitative assessment of the reports, Merck voluntarily added pancreatitis to the post-marketing adverse events section of the labeling for JANUVIA and JANUMET earlier this year as a reported adverse event to make physicians aware of these reports.

The safety profile of JANUVIA and JANUMET has been established through an extensive clinical development program. In addition, in the nearly three years of marketed use, more than 18 million total prescriptions have been dispensed for sitagliptin worldwide.

Merck has published a peer-reviewed analysis of safety data pooled from twelve Phase IIb/III trials in 6,139 patients studied for up to two years in our clinical development program, in which the incidence rates of pancreatitis (0.1% sitagliptin vs. 0% non-exposed), acute pancreatitis (0% vs. 0.1%), and chronic pancreatitis (0.1% vs. 0%) reported in patients treated with sitagliptin were not meaningfully different from that in patients not exposed to sitagliptin.

Merck will continue communicating with patients and healthcare providers about JANUVIA and JANUMET in ways that will help inform their decisions about appropriate treatment choices. Patients should talk with their healthcare providers if they have any questions, and before starting or stopping treatment with any prescription medicine.