The European Medicines Agency’s Committee for Medicinal Products for Human Use has finalised a review of GLP-1-based diabetes therapies and concluded that “presently available data do not confirm recent concerns over an increased risk of pancreatic adverse events with these medicines”.
The drugs in question include glucagon-like peptide-1 (GLP-1) agonists such as Byetta (exenatide), now owned by Bristol-Myers Squibb and AstraZeneca, and Novo Nordisk’s Victoza (liraglutide), but also dipeptidylpeptidase-4 (DPP-4) inhibitors, a class led by Merck & Co’s Januvia (sitagliptin). The CHMP review, and a similar probe in the USA, was initiated following the publication of a study by a group of independent academic researchers that suggested an increased risk of pancreatitis and cellular changes called pancreatic-duct metaplasia in patients with type-2 diabetes treated with GLP-1-based therapies.
Those findings were based on examination of a small number of pancreatic tissue samples obtained from organ donors with and without diabetes mellitus, who died due to causes other than diabetes. However, the CHMP says that the study “had a number of methodological limitations and potential sources of bias, most importantly differences between the studied groups with respect to age, gender, disease duration and treatments, which preclude a meaningful interpretation of the results”.
The CHMP also considered “after a review of all available non-clinical and clinical data that there is no change in evidence regarding the risks of pancreatic adverse events associated with the use of GLP-1 based therapies”. It notes that a small number of cases of pancreatitis have been reported in clinical trials “although these need to be interpreted cautiously” and all these medicines already carry warnings, but the CHMP considered that “there would be value in harmonising the wording of these warnings across all GLP-1 based therapies”
With regard to pancreatic cancer, the committee says that data from clinical trials “do not indicate an increased risk with these medicines [and] the number of events is too small to draw final conclusions”. The CHMP notes that two large independent studies have been under way since 2011 to study the risk profile of diabetes treatments in general, and more specifically in relation to the pancreas.
First results of these studies, which are funded by the European Commission, are expected in the spring of 2014.
