Cancers du pancréas et sécurité des incrétines : état des lieux en 2014

Patients with diabetes, in particular those with type 2 diabetes (T2DM), have an increased risk of developing cancer, particularly pancreatic cancer. The class of incretins, DPP4 inhibitors and GLP-1 receptor agonists, has been suspected to increase the risk of serious pancreatic complications, pancreatitis and pancreatic cancer, first on the basis of proved GLP-1 trophic effects on the exocrine pancreas raising fears of a possible carcinogenic risk. Studies in animal models have reinforced this concern although recent data have questioned these works. Conclusions drawn from data from large registries, FDA in particular, have made the effect of a thunderclap, and histological data published by the same group have found a significant excess risk of pancreatic cancer and precancerous lesions. All findings have been questioned by other analyses of the same data. Large studies with two DPP4 inhibitors (SAVOR-TIMI 53 and EXAMINE) to which today led authorities (FDA, EMA, HAS/Ansm) and scientific societies (ADA, EASD, IDF) to conclude the absence of excess risk of cancer of the pancreas and thyroid in T2DM patients treated with incretin. A huge number of T2DM patients (n >80,000) are now followed to assess cardiovascular safety of the incretin' class. No doubt that cancer will be carefully considered. Prospective studies specifically designed to measure the risk of unwanted effects of incretins have been initiated (SAFEGUARD). At the present time, there is no formal argument in favour of such a risk. However, in my personal opinion, at least by forensic caution, I recommend not to prescribe these drugs in subjects with prior pancreatitis or a family history of pancreatitis, or pancreatic cancer or thyroid medullary carcinoma.