Incretin-based therapies in the treatment of type 2 diabetes--more than meets the eye?

Eur J Intern Med. 2013 Apr;24(3):207-12. doi: 10.1016/j.ejim.2013.01.009. Epub 2013 Jan 31.

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.

Publication types

  • Review

MeSH terms

  • Animals
  • Cell Proliferation / drug effects*
  • Diabetes Mellitus, Type 2 / drug therapy*
  • Diabetes Mellitus, Type 2 / metabolism
  • Drug-Related Side Effects and Adverse Reactions / etiology
  • Drug-Related Side Effects and Adverse Reactions / metabolism
  • Drug-Related Side Effects and Adverse Reactions / prevention & control
  • Gastric Inhibitory Polypeptide* / metabolism
  • Gastric Inhibitory Polypeptide* / pharmacology
  • Gastrointestinal Agents / metabolism
  • Gastrointestinal Agents / pharmacology
  • Glucagon-Like Peptide 1* / metabolism
  • Glucagon-Like Peptide 1* / pharmacology
  • Humans
  • Incretins / metabolism
  • Incretins / pharmacology
  • Insulin / metabolism
  • Models, Animal
  • Neoplasms* / chemically induced
  • Neoplasms* / classification
  • Neoplasms* / metabolism
  • Neoplasms* / prevention & control
  • Outcome Assessment, Health Care
  • Pancreas / drug effects*
  • Pancreas / metabolism
  • Pancreas / physiopathology
  • Pancreatic Diseases* / chemically induced
  • Pancreatic Diseases* / classification
  • Pancreatic Diseases* / epidemiology
  • Pancreatic Diseases* / metabolism
  • Pancreatic Diseases* / prevention & control
  • Randomized Controlled Trials as Topic
  • Rats
  • Risk Factors

Substances

  • Gastrointestinal Agents
  • Incretins
  • Insulin
  • Gastric Inhibitory Polypeptide
  • Glucagon-Like Peptide 1