Acta Scientific Gastrointestinal Disorders (ASGIS)(ISSN: 2582-1091)

Review Article Volume 5 Issue 7

Antidiabetic Drugs: Their Hepatoprotective and Hepatocarcinogenic Effect

Mona A Amin*

Internal Medicine, Hepatogastroenterology, Cairo University, Egypt

*Corresponding Author: Mona A Amin, 1Internal Medicine, Hepatogastroenterology, Cairo University, Egypt.

Received: May 24, 2022; Published: June 21, 2022

Abstract

Hepatocellular carcinoma (HCC) is a major cause of cancer-related death worldwide. Diabetes mellitus (DM), with insulin resistance, is an established independent risk factor for HCC, as reported in multiple observational studies and subsequent meta-analyses.

Current evidence suggests that there may be interplay between obesity, DM, and tumorigenesis, with insulin resistance and hyperinsulinemia playing critical roles.

Given the significant link of DM with the risk of HCC, the use of antidiabetic medications may modify DM and reduce the risk of cancer as shown in recent research. So, the aim of this review is to illustrate the hepatocarcinogenic and hepatoprotective effects of antidiabetic medications on HCC.

Keywords: Antidiabetic Drugs; Hepatoprotective; Hepatocarcinogenic

References

  1. Alessandro Mantovani and Giovanni Targher. “Type 2 diabetes mellitus and risk of hepatocellular carcinoma: spotlight on nonalcoholic fatty liver disease”. Annals of Translational Medicine 13 (2017): 270.
  2. DeCensi M., et al. “Metformin and cancer risk in diabetic patients: a systematic review and metaanalysis”. Cancer Prevention Research11 (2010): 1451-1461.
  3. Guariguata L., et al. “Global estimates of diabetes prevalence for 2013 and projections for 2035”. Diabetes Research and Clinical Practice 103 (2014): 137-149.
  4. Xu Li., et al. “Diabetes Mellitus and Risk of Hepatocellular Carcinoma”. BioMed Research International 2017 (2017): 10.
  5. K Oda., et al. “Clinical features of hepatocellular carcinoma associated with nonalcoholic fatty liver disease: a review of human studies”. Clinical Journal of Gastroenterology 8 (2015): 1-9.
  6. SK Garg., et al. “Diabetes and cancer: two diseases with obesity as a common risk factor”. Diabetes, Obesity and Metabolism 16 (2014): 97-110.
  7. Ong CR., et al. “Long-term efficacy of metformin therapy in nonobese individuals with type 2 diabetes”. Diabetes Care 29 (2006): 2361-2364.
  8. Donadon V., et al. “Metformin and reduced risk of hepatocellular carcinoma in diabetic patients with chronic liver disease”. Liver International 30 (2010): 750-758.
  9. Luo Z., et al. “AMPK as a metabolic tumor suppressor: control of metabolism and cell growth”. Future Oncology 3 (2010): 457-470.
  10. CH Chang., et al. “Association of thiazolidinediones with liver cancer and colorectal cancer in type 2 diabetes mellitus”. Hepatology 5 (2012): 1462-1472.
  11. Wu L., et al. “Pharmacologic therapy of diabetes and overall cancer risk and mortality: A meta-analysis of 265 studies”. Scientific Reports 15 (2015): 10147.
  12. Mao-Yu Huang., et al. “The role of thiazolidinediones in hepatocellular carcinoma risk reduction: a population-based cohort study in Taiwan”. American Journal of Cancer Research 7 (2017): 1606-1616.
  13. Okumura T. “Mechanisms by which thiazolidinediones induce anti-cancer effects in cancers in digestive organs”. Journal of Gastroenterology 45 (2010): 1097-1102.
  14. Drucken D. “Mechanism of action and therapeutic application of Glucagon Like Peptide-1”. Cell Metabolism 27 (2018): 740-756.
  15. Quoyer J., et al. “Glucagon like peptide -1 mediates anti apoptotic effect by phosphorylating Bad through a Beta-Arrestin1- mediated ERK1/2 activation in pancreatic Beta cells 2010”. Journal of Biological Chemistry 285 (2010): 1989-2002.
  16. Wang X., et al. “Effects of Glucagon like peptide-1 receptor agonists on Nonalcoholic fatty liver disease and inflammation”. World Journal of Gastroenterology 40 (2014): 14821-14830.
  17. Gupta NA., et al. “Glucagon like peptide-1 receptor is present on human hepatocytes and has a direct role in decreasing hepatic steatosis in vitro by modulating elements of the insulin signaling pathway”. Hepatology 5 (2010): 1584-1592.
  18. Cao C., et al. “GLP-1 receptor agonists and risk of cancer in type 2 diabetes: an updated meta-analysis of randomized controlled trials”. Endocrine2 (2019): 157-165.
  19. Lui Y., et al. “Risk of malignant neoplasia with Glucagon like peptide-1 receptor agonist treatment in patients with type 2 Diabetes: A meta-analysis”. Journal of Diabetes Research (2019).
  20. Yang X., et al. “Impact of Dipeptidyl peptidase 4 inhibitors on malignant tumors among type 2 diabetes: a network meta analysis”. Cochrane Colloquium Abstracts (2016).
  21. Zhou M., et al. “The antidiabetic drug Exenetide, a Glucagon like peptide-1 receptor agonist counteracts hepatocarcinogenesis through c-AMP = PKA-EGFR-STAT3 axis”. Oncogene 36 (2017): 4135-4147.
  22. Kojima M., et al. “Glucagon like peptide-1 receptor agonist prevented the progression of Hepatocellular Carcinoma in a mouse model of Nonalcoholic steatohepatitis”. International Journal of Molecular Sciences 16 (2020): 5722.
  23. Nuack M. “Do GPL-1 Based therapies increase cancer”. Diabetes Care2 (2013): S245-S252.
  24. Simon TG., et al. “Diabetes, metabolic comorbidities, and risk of hepatocellular carcinoma: Results from two prospective cohort studies”. Hepatology 67 (2018): 1797-1806.
  25. Arase Y., et al. “Effect of sodium glucose cotransporter 2 inhibitors on liver fat mass and body composition in patients with nonalcoholic fatty liver disease and type 2 diabetes mellitus”. Clinical Drug Investigation 39 (2019): 631-641.
  26. Kuchay MS., et al. “Effect of empagliflozin on liver fat in patients with type 2 diabetes and nonalcoholic fatty liver disease: a randomized controlled trial (E-LIFT Trial)”. Diabetes Care 41 (2018): 1801-1808.
  27. Lai LL., et al. “Empagliflozin for the treatment of nonalcoholic steatohepatitis in patients with type 2 diabetes mellitus”. Digestive Diseases and Sciences 65 (2020): 623-631.
  28. Teruo Jojima., et al. “The SGLT2 Inhibitor Canagliflozin Prevents Carcinogenesis in a Mouse Model of Diabetes and Non-Alcoholic Steatohepatitis-Related Hepatocarcinogenesis: Association with SGLT2 Expression in Hepatocellular Carcinoma”. International Journal of Molecular Sciences 20 (2019): 5237.
  29. Nakano D., et al. “Effects of canagliflozin on growth and metabolic reprograming in hepatocellular carcinoma cells: Multi-omics analysis of metabolomics and absolute quantification proteomics (iMPAQT)”. PLoS ONE4 (2020): e0232283.
  30. Man-Hsin Hung., et al. “Canagliflozin inhibits growth of hepatocellular carcinoma via blocking glucose-influx-induced β-catenin activation”. Cell Death and Disease 10 (2019): 420.
  31. Takumi Kawaguchi., et al. “Spontaneous regression of hepatocellular carcinoma with reduction in angiogenesis-related cytokines after treatment with sodium-glucose cotransporter 2 inhibitor in a cirrhotic patient with diabetes mellitus”. Hepatology Research 49 (2019): 479-486.
  32. Donadon V., et al. “Antidiabetic therapy and increased risk of hepatocellular carcinoma in chronic liver disease”. World Journal Gastroenterology20 (2009): 2506-2511.
  33. Proks P., et al. “Sulfonylurea stimulation of insulin secretion”. Diabetes 51 (3 (2000): 5368-5376.
  34. Singh S., et al. “Antidiabetic medication and the risk of Hepatocellular Cancer: a systematic review and meta-analysis”. The American Journal of Gastroenterology 6 (2013): 881-889.
  35. Hassan MM., et al. “Association of diabetes and diabetes treatment with the risk of hepatocellular carcinoma”. Cancer 8 (2010): 1938-1946.
  36. Bosetti C., et al. “Insulin and other antidiabetic drugs and hepatocellular carcinoma risk: a nested case control study based on Italian health care utilization data)”. Pharmacoepidemiology and Drug Safety 7 (2015): 771-778.
  37. Kawaguchi T., et al. “Association of exogenous insulin or sulfonylurea treatment with an increased incidence of Hepatoma in patients with Hepatitis C virus infection”. Liver International 3 (2010): 479-486.
  38. Lee JY., et al. “Incident hepatocellular carcinoma risk in patients treated with a sulfonylurea: a nation wide nested case control study”. Scientific Reports 9 (2019): 8532.
  39. Monami M., et al. “Sulfonylureas and cancer: a case control study”. Acta Diabetologica 4 (2009): 279-284.
  40. Smith V and Gale EA. “Does diabetes therapy influence the risk of cancer?” Diabetologia4 (2009): 1699-1768.
  41. Gallagher EJ and LeRoith D. “Mini review, IGF, Insulin and cancer”. Endocrinology7 (2011): 2546-2551.
  42. Vigneri R., et al. “Insulin, Insulin receptors and Cancer”. Journal of Endocrinological Investigation 12 (2016): 1365-1376.
  43. Belfiori A. “The role of insulin receptor isoforms and hybrid insulin/ IGF-1 receptors in human cancer”. Current Pharmaceutical Design 13 (7 (2007): 671-686.
  44. Frasca F., et al. “Insulin Receptor Isoform A, a newly recognized, high-affinity insulin like growth factor II receptor in fetal and cancer cells”. Molecular and Cellular Biology 5 (1999): 3278-3288.
  45. Shaw LM. “The insulin receptor substrate protein: at the intersection of metabolism and cancer”. Cell Cycle11 (2011): 1750-1756.
  46. Pollack M. “Insulin and Insulin like Growth factor signaling in neoplasia”. Nature Reviews Cancer 12 (2018): 915-928.
  47. Karlstad O., et al. “Use of Insulin and Insulin analogue and risk of cancer - systematic review and meta-analysis of observational studies”. Current Drug Safety 5 (2014): 333-348.
  48. UK Prospective Diabetes study group: “Intensive blood glucose control with sulphonylureas or insulin compared with conventional treatment and risk of complications in patients with Type 2 diabetes”. The Lancet 9131 (1998): 837-853.
  49. The origin trial investigators: “Basal insulin and cardiovascular and other outcomes in Dysglycemia”. The New England Journal of Medicine 367 (2012): 319-328.
  50. Liefvendahl E and Arnqvist HJ. “Mitogenic effect of the insulin analogue glargine in malignant cells in comparison with insulin and IGF-1 Horm”. Metabolism Research 6 (2008): 369-374.
  51. Redwan EM., et al. “Looking at the carcinogenicity of human insulin analogues via the intrinsic disorder prism”. Scientific Report 6 (2016): 23320.
  52. But A., et al. “Cancer risk among insulin users comparing analogues with human insulin in the CARING five -country cohort study”. Diabetologia9 (2017): 1691-1703.
  53. Sakurai Y., et al. “Role of insulin substrates in the progression of hepatocellular carcinoma”. Scientific Reports 7 (2017): 5387.
  54. Baba H., et al. “Facilitatory effect of insulin treatment on hepatocellular carcinoma development in diabetes”. BMC Research Notes1 (2017): 478.

Citation

Citation: Mona A Amin. “Antidiabetic Drugs: Their Hepatoprotective and Hepatocarcinogenic Effect". Acta Scientific Gastrointestinal Disorders 5.7 (2022): 59-66.

Copyright

Copyright: © 2022 Mona A Amin. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.




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