R E J Ryder1. 1. Department of Diabetes and Endocrinology, City Hospital, Birmingham, UK.
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.
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.
Authors: Giuseppe Floresta; George P Keeling; Siham Memdouh; Levente K Meszaros; Rafael T M de Rosales; Vincenzo Abbate Journal: Biomedicines Date: 2021-04-01