The potential risks of pancreatitis and pancreatic cancer with GLP-1-based therapies are far outweighed by the proven and potential (cardiovascular) benefits.
Recent suggestions that glucagon-like peptide-1 (GLP-1)-based therapies could cause pancreatitis, and even pancreatic cancer, are based on:


METHODS
The worrying histological changes are not reproduced in all studies and are unexpectedly variable with different GLP-1-based therapies.
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.
The increased reports of pancreatitis and pancreatic cancer are likely to be attributable to 'notoriety bias'.
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.
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.


CONCLUSIONS
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.
Department of Diabetes and Endocrinology, City Hospital, Birmingham, UK.
R E J
RE
Ryder
D016907:Adverse Drug Reaction Reporting Systems; D002318:Cardiovascular Diseases / Q000209:etiology / Q000517:prevention & control*; D003924:Diabetes Mellitus, Type 2 / Q000150:complications / Q000188:drug therapy* / Q000473:pathology; D003925:Diabetic Angiopathies / Q000517:prevention & control; D054873:Dipeptidyl-Peptidase IV Inhibitors / Q000009:adverse effects / Q000627:therapeutic use; D000077270:Exenatide; D005260:Female; D052216:Glucagon-Like Peptide 1 / Q000009:adverse effects / Q000031:analogs & derivatives / Q000627:therapeutic use; D000067757:Glucagon-Like Peptide-1 Receptor; D006801:Humans; D054795:Incretins / Q000009:adverse effects / Q000627:therapeutic use*; D000069450:Liraglutide; D008297:Male; D010190:Pancreatic Neoplasms / Q000139:chemically induced* / Q000473:pathology; D010195:Pancreatitis / Q000139:chemically induced* / Q000473:pathology; D018579:Patient Selection; D010455:Peptides / Q000009:adverse effects / Q000627:therapeutic use; D016032:Randomized Controlled Trials as Topic; D018027:Receptors, Glucagon / Q000819:agonists*; D018570:Risk Assessment; D012307:Risk Factors; D014688:Venoms / Q000009:adverse effects / Q000627:therapeutic use; D000067758:Glucagon-Like Peptide-2 Receptor
D054873:Dipeptidyl-Peptidase IV Inhibitors; D000077270:Exenatide; D052216:Glucagon-Like Peptide 1; D000067757:Glucagon-Like Peptide-1 Receptor; D054795:Incretins; D000069450:Liraglutide; D010455:Peptides; D018027:Receptors, Glucagon; D014688:Venoms; C000593833:GLP1R protein, human; C479460:lixisenatide; D000067758:Glucagon-Like Peptide-2 Receptor