title: Incretin-based therapies in the treatment of type 2 diabetes--more than meets the eye?
abstract: A lot of contradictory data regarding the serious side effects of incretin-based therapies are currently available, with more being prepared or published every month. Considering the widespread use of these drugs it should be considered a priority to establish both short- and long-term risks connected with incretin treatment. We performed an extensive literature search of the PubMed database looking for articles dealing with connections between incretin-based therapies and pancreatitis, pancreatic cancer, thyroid cancer and other neoplasms. Data obtained indicate that GLP-1 agonists and DPPIV inhibitors could increase the risk of pancreatitis and pancreatic cancer, possibly due to their capacity to increase ductal cell turnover, which has previously been found to be up-regulated in patients with obesity and T2DM. GLP-1 analogues exenatide and liraglutide seem to be connected with medullary thyroid carcinoma in rat models and, surprisingly, GLP-1 receptors have been found in papillary thyroid carcinoma, currently the most common neoplasm of the thyroid gland in humans. Changes in expression of DPPIV have been described in ovarian carcinoma, melanoma, endometrial adenocarcinoma, prostate cancer, non-small cell lung cancer and in certain haematological malignancies. In most cases loss of DPPIV activity is connected with a higher grading scale, more aggressive tumour behaviour and higher metastatic potential. In conclusion animal and human studies indicate that there could be a connection between incretin-based therapies and pancreatitis, pancreatic cancer, thyroid cancer and other neoplasms. Therefore whenever such therapy is started it would be wise to proceed with caution, especially if personal history of neoplasms is present.
authors: Department of Internal Medicine and Clinical Pharmacology, Medical University of Silesia, Medyków 18, Katowice, Poland.
authors: Krzysztof
authors: K
authors: Labuzek
authors: Michał
authors: M
authors: Kozłowski
authors: Dawid
authors: D
authors: Szkudłapski
authors: Patrycja
authors: P
authors: Sikorska
authors: Monika
authors: M
authors: Kozłowska
authors: Bogusław
authors: B
authors: Okopień
mesh_terms: D000818:Animals; D049109:Cell Proliferation / Q000187:drug effects*; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy* / Q000378:metabolism; D064420:Drug-Related Side Effects and Adverse Reactions / Q000209:etiology / Q000378:metabolism / Q000517:prevention & control; D005749:Gastric Inhibitory Polypeptide / Q000378:metabolism / Q000494:pharmacology; D005765:Gastrointestinal Agents / Q000378:metabolism / Q000494:pharmacology; D052216:Glucagon-Like Peptide 1 / Q000378:metabolism / Q000494:pharmacology; D006801:Humans; D054795:Incretins / Q000378:metabolism / Q000494:pharmacology; D007328:Insulin / Q000378:metabolism; D023421:Models, Animal; D009369:Neoplasms / Q000139:chemically induced / Q000145:classification / Q000378:metabolism / Q000517:prevention & control; D017063:Outcome Assessment, Health Care; D010179:Pancreas / Q000187:drug effects* / Q000378:metabolism / Q000503:physiopathology; D010182:Pancreatic Diseases / Q000139:chemically induced / Q000145:classification / Q000453:epidemiology / Q000378:metabolism / Q000517:prevention & control; D016032:Randomized Controlled Trials as Topic; D051381:Rats; D012307:Risk Factors
chemical_list: D005765:Gastrointestinal Agents; D054795:Incretins; D007328:Insulin; D005749:Gastric Inhibitory Polypeptide; D052216:Glucagon-Like Peptide 1