567
Views
14
CrossRef citations to date
0
Altmetric
Reviews

Are incretin mimetics and enhancers linked to pancreatitis and malignant transformations in pancreas?

&

Bibliography

  • Drucker DJ, Nauck MA. The incretin system: glucagon-like peptide-1 receptor agonists and dipeptidyl peptidase-4 inhibitors in type 2 diabetes. Lancet 2006;368(9548):1696-705
  • Nauck MA. Incretin-based therapies for type 2 diabetes mellitus: properties, functions, and clinical implications. Am J Med 2011;124(1 Suppl):S3-18
  • Deacon CF, Holst JJ. Dipeptidyl peptidase-4 inhibitors for the treatment of type 2 diabetes: comparison, efficacy and safety. Expert Opin Pharmacother 2013;14(15):2047-58
  • Inzucchi SE, Bergenstal RM, Buse JB, et al. Management of hyperglycaemia in type 2 diabetes: a patient-centered approach. Position statement of the American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD). Diabetologia 2012;55(6):1577-96
  • Dunning BE, Gerich JE. The role of alpha-cell dysregulation in fasting and postprandial hyperglycemia in type 2 diabetes and therapeutic implications. Endocr Rev 2007;28(3):253-83
  • Elashoff M, Matveyenko AV, Gier B, et al. Pancreatitis, Pancreatic and thyroid Cancer with Glucagon-Like Peptide-1-Based Therapies. Gastroenterology 2011;141(1):150-6
  • Singh S, Chang HY, Richards TM, et al. Glucagonlike peptide 1-based therapies and risk of hospitalization for acute pancreatitis in type 2 diabetes mellitus: a population-based matched case-control study. JAMA Intern Med 2013;173(7):534-9
  • Butler PC, Elashoff M, Elashoff R, Gale EA. A critical analysis of the clinical use of incretin-based therapies: are the GLP-1 therapies safe? Diabetes Care 2013;36(7):2118-25
  • Gier B, Matveyenko AV, Kirakossian D, et al. Chronic GLP-1 receptor activation by exendin-4 induces expansion of pancreatic duct glands in rats and accelerates formation of dysplastic lesions and chronic pancreatitis in the Kras(G12D) mouse model. Diabetes 2012;61(5):1250-62
  • Butler AE, Campbell-Thompson M, Gurlo T, et al. Marked expansion of exocrine and endocrine pancreas with incretin therapy in humans with increased exocrine pancreas dysplasia and the potential for glucagon-producing neuroendocrine tumors. Diabetes 2013;62(7):2595-604
  • Scirica BM, Bhatt DL, Braunwald E, et al. Saxagliptin and Cardiovascular Outcomes in Patients with Type 2 Diabetes Mellitus. N Engl J Med 2013;369(14):1317-26
  • White WB, Cannon CP, Heller SR, et al. Alogliptin after acute coronary syndrome in patients with type 2 diabetes. N Engl J Med 2013;369(14):1327-35
  • Hardt PD, Brendel MD, Kloer HU, Bretzel RG. Is pancreatic diabetes (type 3c diabetes) underdiagnosed and misdiagnosed? Diabetes Care 2008;31(Suppl 2):S165-9
  • Girman CJ, Kou TD, Cai B, et al. Patients with type 2 diabetes mellitus have higher risk for acute pancreatitis compared with those without diabetes. Diabetes Obes Metab 2010;12(9):766-71
  • Lai SW, Muo CH, Liao KF, et al. Risk of acute pancreatitis in type 2 diabetes and risk reduction on anti-diabetic drugs: a population-based cohort study in Taiwan. Am J Gastroenterol 2011;106(9):1697-704
  • Noel RA, Braun DK, Patterson RE, Bloomgren GL. Increased risk of acute pancreatitis and biliary disease observed in patients with type 2 diabetes: a retrospective cohort study. Diabetes Care 2009;32(5):834-8
  • Gonzalez-Perez A, Schlienger RG, Rodriguez LA. Acute pancreatitis in association with type 2 diabetes and antidiabetic drugs: a population-based cohort study. Diabetes Care 2010;33(12):2580-5
  • Shen HN, Chang YH, Chen HF, et al. Increased risk of severe acute pancreatitis in patients with diabetes. Diabet Med 2012;29(11):1419-24
  • Whitcomb DC. Clinical practice. Acute pancreatitis. N Engl J Med 2006;354(20):2142-50
  • Spanier BW, Dijkgraaf MG, Bruno MJ. Epidemiology, aetiology and outcome of acute and chronic pancreatitis: an update. Best Pract Res Clin Gastroenterol 2008;22(1):45-63
  • Cornier MA, Dabelea D, Hernandez TL, et al. The metabolic syndrome. Endocr Rev 2008;29(7):777-822
  • Shaffer EA. Gallstone disease: epidemiology of gallbladder stone disease. Best Pract Res Clin Gastroenterol 2006;20(6):981-96
  • Pagliarulo M, Fornari F, Fraquelli M, et al. Gallstone disease and related risk factors in a large cohort of diabetic patients. Dig Liver Dis 2004;36(2):130-4
  • Badalov N, Baradarian R, Iswara K, et al. Drug-induced acute pancreatitis: an evidence-based review. Clin Gastroenterol Hepatol 2007;5(6):648-61. quiz 644
  • Yang L, He Z, Tang X, Liu J. Type 2 diabetes mellitus and the risk of acute pancreatitis: a meta-analysis. Eur J Gastroenterol Hepatol 2013;25(2):225-31
  • Solanki NS, Barreto SG, Saccone GT. Acute pancreatitis due to diabetes: the role of hyperglycaemia and insulin resistance. Pancreatology 2012;12(3):234-9
  • Gukovsky I, Li N, Todoric J, et al. Inflammation, autophagy, and obesity: common features in the pathogenesis of pancreatitis and pancreatic cancer. Gastroenterology 2013;144(6):1199-209. e4
  • Park J, Euhus DM, Scherer PE. Paracrine and endocrine effects of adipose tissue on cancer development and progression. Endocr Rev 2011;32(4):550-70
  • Giovannucci E, Harlan DM, Archer MC, et al. Diabetes and cancer: a consensus report. Diabetes Care 2010;33(7):1674-85
  • Vigneri P, Frasca F, Sciacca L, et al. Diabetes and cancer. Endocr Relat Cancer 2009;16(4):1103-23
  • Muniraj T, Chari ST. Diabetes and pancreatic cancer. Minerva Gastroenterol Dietol 2012;58(4):331-45
  • Vincent A, Herman J, Schulick R, et al. Pancreatic cancer. Lancet 2011;378(9791):607-20
  • Calle EE, Rodriguez C, Walker-Thurmond K, Thun MJ. Overweight, obesity, and mortality from cancer in a prospectively studied cohort of U.S. adults. N Engl J Med 2003;348(17):1625-38
  • Ben Q, Xu M, Ning X, et al. Diabetes mellitus and risk of pancreatic cancer: a meta-analysis of cohort studies. Eur J Cancer 2011;47(13):1928-37
  • Brodovicz KG, Kou TD, Alexander CM, et al. Impact of diabetes duration and chronic pancreatitis on the association between type 2 diabetes and pancreatic cancer risk. Diabetes Obes Metab 2012;14(12):1123-8
  • Zechner D, Knapp N, Bobrowski A, et al. Diabetes increases pancreatic fibrosis during chronic inflammation. Exp Biol Med (Maywood) 2014;239(6):670-6
  • Rosen ED, Spiegelman BM. Adipocytes as regulators of energy balance and glucose homeostasis. Nature 2006;444(7121):847-53
  • Giorda CB, Nada E, Tartaglino B, et al. A systematic review of acute pancreatitis as an adverse event of type 2 diabetes drugs: from hard facts to a balanced position. Diabetes Obes Metab 2014. [ Epub ahead of print]
  • Blomgren KB, Sundstrom A, Steineck G, Wiholm BE. Obesity and treatment of diabetes with glyburide may both be risk factors for acute pancreatitis. Diabetes Care 2002;25(2):298-302
  • Noto H, Goto A, Tsujimoto T, Noda M. Cancer risk in diabetic patients treated with metformin: a systematic review and meta-analysis. PLoS One 2012;7(3):e33411
  • Soranna D, Scotti L, Zambon A, et al. Cancer risk associated with use of metformin and sulfonylurea in type 2 diabetes: a meta-analysis. Oncologist 2012;17(6):813-22
  • Lin HC, Hsu YT, Kachingwe BH, et al. Dose effect of thiazolidinedione on cancer risk in type 2 diabetes mellitus patients: a six-year population-based cohort study. J Clin Pharm Ther 2014;39(4):354-60
  • Bowker SL, Majumdar SR, Veugelers P, Johnson JA. Increased cancer-related mortality for patients with type 2 diabetes who use sulfonylureas or insulin. Diabetes Care 2006;29(2):254-8
  • Chang CH, Lin JW, Wu LC, et al. Oral insulin secretagogues, insulin, and cancer risk in type 2 diabetes mellitus. J Clin Endocrinol Metab 2012;97(7):E1170-5
  • Currie CJ, Poole CD, Gale EA. The influence of glucose-lowering therapies on cancer risk in type 2 diabetes. Diabetologia 2009;52(9):1766-77
  • Home PD, Kahn SE, Jones NP, et al. Experience of malignancies with oral glucose-lowering drugs in the randomised controlled ADOPT (A Diabetes Outcome Progression Trial) and RECORD (Rosiglitazone Evaluated for Cardiovascular Outcomes and Regulation of Glycaemia in Diabetes) clinical trials. Diabetologia 2010;53(9):1838-45
  • Li D, Yeung SC, Hassan MM, et al. Antidiabetic therapies affect risk of pancreatic cancer. Gastroenterology 2009;137(2):482-8
  • Ruiter R, Visser LE, van Herk-Sukel MP, et al. Lower risk of cancer in patients on metformin in comparison with those on sulfonylurea derivatives: results from a large population-based follow-up study. Diabetes Care 2012;35(1):119-24
  • Bodmer M, Becker C, Meier C, et al. Use of antidiabetic agents and the risk of pancreatic cancer: a case-control analysis. Am J Gastroenterol 2012;107(4):620-6
  • Singh S, Singh PP, Singh AG, et al. Anti-diabetic medications and risk of pancreatic cancer in patients with diabetes mellitus: a systematic review and meta-analysis. Am J Gastroenterol 2013;108(4):510-19. quiz 20
  • Pollak M. The insulin and insulin-like growth factor receptor family in neoplasia: an update. Nat Rev Cancer 2012;12(3):159-69
  • Feng YH, Velazquez-Torres G, Gully C, et al. The impact of type 2 diabetes and antidiabetic drugs on cancer cell growth. J Cell Mol Med 2011;15(4):825-36
  • Xu G, Stoffers DA, Habener JF, Bonner-Weir S. Exendin-4 stimulates both beta-cell replication and neogenesis, resulting in increased beta-cell mass and improved glucose tolerance in diabetic rats. Diabetes 1999;48(12):2270-6
  • Butler PC, Matveyenko AV, Dry S, et al. Glucagon-like peptide-1 therapy and the exocrine pancreas: innocent bystander or friendly fire? Diabetologia 2010;53(1):1-6
  • Matveyenko AV, Dry S, Cox HI, et al. Beneficial endocrine but adverse exocrine effects of sitagliptin in the human islet amyloid polypeptide transgenic rat model of type 2 diabetes: interactions with metformin. Diabetes 2009;58(7):1604-15
  • Nachnani JS, Bulchandani DG, Nookala A, et al. Biochemical and histological effects of exendin-4 (exenatide) on the rat pancreas. Diabetologia 2010;53(1):153-9
  • Tatarkiewicz K, Smith PA, Sablan EJ, et al. Exenatide does not evoke pancreatitis and attenuates chemically induced pancreatitis in normal and diabetic rodents. Am J Physiol Endocrinol Metab 2010;299(6):E1076-86
  • Koehler JA, Baggio LL, Lamont BJ, et al. Glucagon-like peptide-1 receptor activation modulates pancreatitis-associated gene expression but does not modify the susceptibility to experimental pancreatitis in mice. Diabetes 2009;58(9):2148-61
  • Aston-Mourney K, Subramanian SL, Zraika S, et al. One year of sitagliptin treatment protects against islet amyloid-associated beta-cell loss and does not induce pancreatitis or pancreatic neoplasia in mice. Am J Physiol Endocrinol Metab 2013;305(4):E475-84
  • Forest T, Holder D, Smith A, et al. Characterization of the exocrine pancreas in the male Zucker diabetic fatty rat model of type 2 diabetes mellitus following 3 months of treatment with sitagliptin. Endocrinology 2014;155(3):783-92
  • Busch SJ, Hoffmann P, Sahota P, et al. Studies in rodents with the dipeptidyl peptidase-4 inhibitor vildagliptin to evaluate possible drug-induced pancreatic histological changes that are predictive of pancreatitis and cancer development in man. Diabetes Obes Metab 2013;15(1):72-6
  • Engel SS, Williams-Herman DE, Golm GT, et al. Sitagliptin: review of preclinical and clinical data regarding incidence of pancreatitis. Int J Clin Pract 2010;64(7):984-90
  • Nyborg NC, Molck AM, Madsen LW, Knudsen LB. The human GLP-1 analog liraglutide and the pancreas: evidence for the absence of structural pancreatic changes in three species. Diabetes 2012;61(5):1243-9
  • Tatarkiewicz K, Belanger P, Gu G, et al. No evidence of drug-induced pancreatitis in rats treated with exenatide for 13 weeks. Diabetes Obes Metab 2013;15(5):417-26
  • Vrang N, Jelsing J, Simonsen L, et al. The effects of 13 wk of liraglutide treatment on endocrine and exocrine pancreas in male and female ZDF rats: a quantitative and qualitative analysis revealing no evidence of drug-induced pancreatitis. Am J Physiol Endocrinol Metab 2012;15:303(2):E253-64
  • Holst JJ. Pancreatic safety of GLP-1-based therapeutic agents: further insights from rodent studies? Diabetologia 2013;56(9):1869-72
  • Lamont BJ, Andrikopoulos S. Hope and fear for new classes of type 2 diabetes drugs: is there preclinical evidence that incretin-based therapies alter pancreatic morphology? J Endocrinol 2014;221(1):T43-61
  • Chadwick KD, Fletcher AM, Parrula MC, et al. Occurrence of spontaneous pancreatic lesions in normal and diabetic rats: a potential confounding factor in the nonclinical assessment of GLP-1-based therapies. Diabetes 2014;63(4):1303-14
  • Gale EA. GLP-1-based therapies and the exocrine pancreas: more light, or just more heat? Diabetes 2012;61(5):986-8
  • Egan AG, Blind E, Dunder K, et al. Pancreatic safety of incretin-based drugs--FDA and EMA assessment. N Engl J Med 2014;370(9):794-7
  • FDA UFaDA. Information for Healthcare Professionals: Exenatide (marketed as Byetta) - 8/2008 Update. 2008. Available from: http://www.fda.gov/Drugs/DrugSafety/PostmarketDrugSafetyInformationforPatientsandProviders/ucm124713.htm [cited 03.03.2014]
  • Ahmad SR, Swann J. Exenatide and rare adverse events. N Engl J Med 2008;358(18):1970-1. discussion 71-2
  • FDA UFaDA. Information for Healthcare Professionals - Acute pancreatitis and sitagliptin (marketed as Januvia and Janumet). 2009
  • Weaver J, Willy M, Avigan M. Informatic tools and approaches in postmarketing pharmacovigilance used by FDA. AAPS J 2008;10(1):35-41
  • Raschi E, Piccinni C, Poluzzi E, et al. The association of pancreatitis with antidiabetic drug use: gaining insight through the FDA pharmacovigilance database. Acta Diabetol 2013;50(4):569-77
  • Cohen D. Reports of pancreatitis are 20-30 times more likely with GLP-1 drugs, analysis finds. BMJ 2013;346:f2607
  • Faillie JL, Babai S, Crepin S, et al. Pancreatitis associated with the use of GLP-1 analogs and DPP-4 inhibitors: a case/non-case study from the French Pharmacovigilance Database. Acta Diabetol 2013;51(3):491-7
  • Giorda CB, Picariello R, Nada E, et al. Incretin therapies and risk of hospital admission for acute pancreatitis in an unselected population of European patients with type 2 diabetes: a case-control study. Lancet Diabetes Endocrinol 2014;2(2):111-15
  • Chou HC, Chen WW, Hsiao FY. Acute pancreatitis in patients with type 2 diabetes mellitus treated with dipeptidyl peptidase-4 inhibitors: a population-based nested case-control study. Drug Saf 2014;37(7):521-8
  • Li X, Zhang Z, Duke J. Glucagon-like peptide 1-based therapies and risk of pancreatitis: a self-controlled case series analysis. Pharmacoepidemiol Drug Saf 2014;23(3):234-9
  • EMA. Investigation into GLP-1-based diabetes therapies concluded. 2013. Available from the EMA website http://www.ema.europa.eu/ema/index.jsp?curl=pages/news_and_events/news/2013/07/news_detail_001856.jsp&mid=WC0b01ac058004d5c1
  • FDA USFaDA. FDA Drug Safety Communication: FDA investigating reports of possible increased risk of pancreatitis and pre-cancerous findings of the pancreas from incretin mimetic drugs for type 2 diabetes. 2013. Available from the FDA website http://www.fda.gov/drugs/drugsafety/ucm343187.htm
  • Engel SS, Golm GT, Lauring B. Comment on: butler et al. Marked expansion of exocrine and endocrine pancreas with incretin therapy in humans with increased exocrine pancreas dysplasia and the potential for glucagon-producing neuroendocrine tumors. Diabetes 2013;62:2595-2604. Diabetes 2013;62(10):e18
  • Heine RJ, Fu H, Kendall DM, Moller DE. Comment on: butler et al. Marked expansion of exocrine and endocrine pancreas with incretin therapy in humans with increased exocrine pancreas dysplasia and the potential for glucagon-producing neuroendocrine tumors. Diabetes 2013;62:2595-604.Diabetes 2013;62(10):e16-17
  • Saisho Y, Butler AE, Meier JJ, et al. Pancreas volumes in humans from birth to age one hundred taking into account sex, obesity, and presence of type-2 diabetes. Clin Anat 2007;20(8):933-42
  • In’t Veld P, De Munck N, Van Belle K, et al. Beta-cell replication is increased in donor organs from young patients after prolonged life support. Diabetes 2010;59(7):1702-8
  • Williams AJ, Thrower SL, Sequeiros IM, et al. Pancreatic volume is reduced in adult patients with recently diagnosed type 1 diabetes. J Clin Endocrinol Metab 2012;97(11):E2109-13
  • Stelow EB, Adams RB, Moskaluk CA. The prevalence of pancreatic intraepithelial neoplasia in pancreata with uncommon types of primary neoplasms. Am J Surg Pathol 2006;30(1):36-41
  • Andea A, Sarkar F, Adsay VN. Clinicopathological correlates of pancreatic intraepithelial neoplasia: a comparative analysis of 82 cases with and 152 cases without pancreatic ductal adenocarcinoma. Mod Pathol 2003;16(10):996-1006
  • Bonner-Weir S, In’t Veld PA, Weir GC. Reanalysis of study of pancreatic effects of incretin therapy: methodological deficiencies. Diabetes Obes Metab 2014;16(7):661-6
  • Dore DD, Seeger JD, Arnold Chan K. Use of a claims-based active drug safety surveillance system to assess the risk of acute pancreatitis with exenatide or sitagliptin compared to metformin or glyburide. Curr Med Res Opin 2009;25(4):1019-27
  • Dore DD, Bloomgren GL, Wenten M, et al. A cohort study of acute pancreatitis in relation to exenatide use. Diabetes Obes Metab 2011;13(6):559-66
  • Garg R, Chen W, Pendergrass M. Acute pancreatitis in type 2 diabetes treated with exenatide or sitagliptin: a retrospective observational pharmacy claims analysis. Diabetes Care 2010;33(11):2349-54
  • Romley JA, Goldman DP, Solomon M, et al. Exenatide therapy and the risk of pancreatitis and pancreatic cancer in a privately insured population. Diabetes Technol Ther 2012;14(10):904-11
  • Wenten M, Gaebler JA, Hussein M, et al. Relative risk of acute pancreatitis in initiators of exenatide twice daily compared with other anti-diabetic medication: a follow-up study. Diabet Med 2012;29(11):1412-18
  • Funch D, Gydesen H, Tornoe K, et al. A prospective, claims-based assessment of the risk of pancreatitis and pancreatic cancer with liraglutide compared to other antidiabetic drugs. Diabetes Obes Metab 2014;16(3):273-5
  • Faillie JL, Azoulay L, Patenaude V, et al. Incretin based drugs and risk of acute pancreatitis in patients with type 2 diabetes: cohort study. BMJ 2014;348:g2780
  • Monami M, Dicembrini I, Mannucci E. Dipeptidyl peptidase-4 inhibitors and pancreatitis risk: a meta-analysis of randomized clinical trials. Diabetes Obes Metab 2014;16(1):48-56
  • Monami M, Dicembrini I, Martelli D, Mannucci E. Safety of dipeptidyl peptidase-4 inhibitors: a meta-analysis of randomized clinical trials. Curr Med Res Opin 2011;27(Suppl 3):57-64
  • Alves C, Batel-Marques F, Macedo AF. A meta-analysis of serious adverse events reported with exenatide and liraglutide: acute pancreatitis and cancer. Diabetes Res Clin Pract 2012;98(2):271-84
  • Monami M, Dicembrini I, Nardini C, et al. Glucagon-like peptide-1 receptor agonists and pancreatitis: a meta-analysis of randomized clinical trials. Diabetes Res Clin Pract 2014;103(2):269-75
  • Scheen A. Gliptins (dipeptidyl peptidase-4 inhibitors) and risk of acute pancreatitis. Expert Opin Drug Saf 2013;12(4):545-57
  • Li L, Shen J, Bala MM, et al. Incretin treatment and risk of pancreatitis in patients with type 2 diabetes mellitus: systematic review and meta-analysis of randomised and non-randomised studies. BMJ 2014;348:g2366
  • Meier JJ, Nauck MA. Risk of pancreatitis in patients treated with incretin-based therapies. Diabetologia 2014;57(7):1320-4
  • Yachida S, Jones S, Bozic I, et al. Distant metastasis occurs late during the genetic evolution of pancreatic cancer. Nature 2010;467(7319):1114-17
  • Available from: http://www.fda.gov/and http://www.ema.europa.eu/ema/
  • Available from: https://www.clinicaltrials.gov

Reprints and Corporate Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

To request a reprint or corporate permissions for this article, please click on the relevant link below:

Academic Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

Obtain permissions instantly via Rightslink by clicking on the button below:

If you are unable to obtain permissions via Rightslink, please complete and submit this Permissions form. For more information, please visit our Permissions help page.