The potential risks of pancreatitis and pancreatic cancer with GLP‐1‐based therapies are far outweighed by the proven and potential (cardiovascular) benefits

Abstract Recent suggestions that glucagon‐like peptide‐1 (GLP‐1)‐based therapies could cause pancreatitis, and even pancreatic cancer, are based on: Animal studies The worrying histological changes are not reproduced in all studies and are unexpectedly variable with different GLP‐1‐based therapies. An observational study Singh's findings that pancreatitis is doubled with GLP‐1‐based therapies could relate to their use in obese patients who are prone to pancreatitis risk factors—gallstones and hypertriglyceridaemia. The other observational studies do not find an association between GLP‐1‐based therapies and pancreatitis. US Food and Drug Administration adverse event reporting system The increased reports of pancreatitis and pancreatic cancer are likely to be attributable to ‘notoriety bias’. A study of organ donor pancreases Butler's findings for those on GLP‐1‐based therapies vs. those not, could have other explanations. Meanwhile: Meta analysis Randomized control trials with GLP‐1‐based therapies do not find increased pancreatitis risk. Meta‐analysis of 53 randomized controlled trials including 20 212 dipeptidyl peptidase‐4 inhibitor‐treated patients found a significantly reduced risk of major adverse cardiovascular events [odds ratio 0.689 (0.528–0.899), P = 0.006] for dipeptidyl peptidase‐4 inhibitors compared with control subjects. Cardiovascular risk The evidence suggests that there is more than a possibility that some of the GLP‐1 receptor agonists, and possibly also some dipeptidyl peptidase‐4 inhibitors, may be associated with reduced cardiovascular events. Eight ongoing long‐term cardiovascular randomized controlled trials will report from September 2013 onwards. These trials should resolve the issue of pancreatitis risk and substantiate the extent of benefit. Conclusion Whilst we should remain vigilant, currently the balance of evidence is strongly in support of GLP‐1‐based therapy, with benefits far outweighing potential risks.