open access

Vol 72, No 4 (2021)
Review paper
Submitted: 2021-04-02
Accepted: 2021-06-24
Published online: 2021-07-28
Get Citation

Treatment of type 2 diabetes mellitus and risk of pancreatic cancer

Edyta Olakowska1, Marek Olakowski2
DOI: 10.5603/EP.a2021.0069
·
Pubmed: 34410681
·
Endokrynologia Polska 2021;72(4):395-401.
Affiliations
  1. Department of Physiology, Medyków 18, 40-752 Katowice, Poland
  2. Department of Gastrointestinal Surgery, Medical University of Silesia, Katowice, Poland

open access

Vol 72, No 4 (2021)
Review Article
Submitted: 2021-04-02
Accepted: 2021-06-24
Published online: 2021-07-28

Abstract

Pancreatic ductal adenocarcinoma (PDAC) is the most common cancer of the exocrine part of the pancreas with poor prognosis. Up to 85% of PDAC patients are diagnosed with diabetes or hyperglycaemia at the time of diagnosis indicating that impaired glucose homeostasis is a common event in this cancer. A mechanism of association between PDAC and diabetes is very complex and still not fully understood. Currently, the various classes of anti-diabetic drugs are used in diabetes treatment. It is possible that specific types of anti-diabetic drugs for diabetes may have different impacts on pancreatic cancer development. Moreover, the intriguing question of whether diabetes can facilitate PDAC development remains unanswered. This paper presents the results of recent studies on the effect of the anti-diabetic treatment used on pancreatic cancer risk in diabetic patients.

Abstract

Pancreatic ductal adenocarcinoma (PDAC) is the most common cancer of the exocrine part of the pancreas with poor prognosis. Up to 85% of PDAC patients are diagnosed with diabetes or hyperglycaemia at the time of diagnosis indicating that impaired glucose homeostasis is a common event in this cancer. A mechanism of association between PDAC and diabetes is very complex and still not fully understood. Currently, the various classes of anti-diabetic drugs are used in diabetes treatment. It is possible that specific types of anti-diabetic drugs for diabetes may have different impacts on pancreatic cancer development. Moreover, the intriguing question of whether diabetes can facilitate PDAC development remains unanswered. This paper presents the results of recent studies on the effect of the anti-diabetic treatment used on pancreatic cancer risk in diabetic patients.

Get Citation

Keywords

pancreatic cancer; type 2 diabetes mellitus; anti-diabetic medication; pancreatic cancer risk

About this article
Title

Treatment of type 2 diabetes mellitus and risk of pancreatic cancer

Journal

Endokrynologia Polska

Issue

Vol 72, No 4 (2021)

Article type

Review paper

Pages

395-401

Published online

2021-07-28

DOI

10.5603/EP.a2021.0069

Pubmed

34410681

Bibliographic record

Endokrynologia Polska 2021;72(4):395-401.

Keywords

pancreatic cancer
type 2 diabetes mellitus
anti-diabetic medication
pancreatic cancer risk

Authors

Edyta Olakowska
Marek Olakowski

References (65)
  1. Paternoster S, Falasca M. The intricate relationship between diabetes, obesity and pancreatic cancer. Biochim Biophys Acta Rev Cancer. 2020; 1873(1): 188326.
  2. Bray F, Ferlay J, Soerjomataram I, et al. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2018; 68(6): 394–424.
  3. Wojciechowska U, Czaderny K, Ciuba A, Olasek P, Didkowska J. Cancer in Poland in 2016. Krajowy Rejestr Nowotworów, Warszawa 2018.
  4. Siegel RL, Miller KD, Fuchs HE, et al. Cancer Statistics, 2021. CA Cancer J Clin. 2021; 71(1): 7–33.
  5. Rahib L, Smith BD, Aizenberg R, et al. Projecting cancer incidence and deaths to 2030: the unexpected burden of thyroid, liver, and pancreas cancers in the United States. Cancer Res. 2014; 74(11): 2913–2921.
  6. Lu Ye, Gentiluomo M, Lorenzo-Bermejo J, et al. Mendelian randomisation study of the effects of known and putative risk factors on pancreatic cancer. J Med Genet. 2020; 57(12): 820–828.
  7. Li D. Diabetes and pancreatic cancer. Mol Carcinog. 2012; 51(1): 64–74.
  8. Galicia-Garcia U, Benito-Vicente A, Jebari S, et al. Pathophysiology of Type 2 Diabetes Mellitus. Int J Mol Sci. 2020; 21(17).
  9. DeFronzo RA, Ferrannini E, Groop L, et al. Type 2 diabetes mellitus. Nat Rev Dis Primers. 2015; 1: 15019.
  10. Araszkiewicz A, Bandurska-Stankiewicz E, Budzyński A, et al. 2019 Guidelines on the management of diabetic patients. A position of Diabetes Poland. Clin Diabetol. 2019; 8(1): 1–95.
  11. Andersen DK, Korc M, Petersen GM, et al. Diabetes, Pancreatogenic Diabetes, and Pancreatic Cancer. Diabetes. 2017; 66(5): 1103–1110.
  12. Singhi AD, Koay EJ, Chari ST, et al. Early Detection of Pancreatic Cancer: Opportunities and Challenges. Gastroenterology. 2019; 156(7): 2024–2040.
  13. Pang Y, Kartsonaki C, Guo Yu, et al. Diabetes, plasma glucose and incidence of pancreatic cancer: A prospective study of 0.5 million Chinese adults and a meta-analysis of 22 cohort studies. Int J Cancer. 2017; 140(8): 1781–1788.
  14. Sah RP, Nagpal SJ, Mukhopadhyay D, et al. New insights into pancreatic cancer-induced paraneoplastic diabetes. Nat Rev Gastroenterol Hepatol. 2013; 10(7): 423–433.
  15. Sharma A, Kandlakunta H, Nagpal SJ, et al. Model to Determine Risk of Pancreatic Cancer in Patients With New-Onset Diabetes. Gastroenterology. 2018; 155(3): 730–739.e3.
  16. Shafiei-Irannejad V, Samadi N, Salehi R, et al. New insights into antidiabetic drugs: Possible applications in cancer treatment. Chem Biol Drug Des. 2017; 90(6): 1056–1066.
  17. Pollak M. The insulin and insulin-like growth factor receptor family in neoplasia: an update. Nat Rev Cancer. 2012; 12(3): 159–169.
  18. Menini S, Iacobini C, Vitale M, et al. Diabetes and Pancreatic Cancer-A Dangerous Liaison Relying on Carbonyl Stress. Cancers (Basel). 2021; 13(2).
  19. Hu CM, Tien SC, Hsieh PK, et al. High Glucose Triggers Nucleotide Imbalance through O-GlcNAcylation of Key Enzymes and Induces KRAS Mutation in Pancreatic Cells. Cell Metab. 2019; 29(6): 1334–1349.e10.
  20. Rahn S, Zimmermann V, Viol F, et al. Diabetes as risk factor for pancreatic cancer: Hyperglycemia promotes epithelial-mesenchymal-transition and stem cell properties in pancreatic ductal epithelial cells. Cancer Lett. 2018; 415: 129–150.
  21. Mannucci E. Insulin therapy and cancer in type 2 diabetes. ISRN Endocrinol. 2012; 2012: 240634.
  22. Tokajuk A, Krzyżanowska-Grycel E, Tokajuk A, et al. Antidiabetic drugs and risk of cancer. Pharmacol Rep. 2015; 67(6): 1240–1250.
  23. Li D, Yeung SCJ, Hassan MM, et al. Antidiabetic therapies affect risk of pancreatic cancer. Gastroenterology. 2009; 137(2): 482–488.
  24. Bosetti C, Rosato V, Li D, et al. Diabetes, antidiabetic medications, and pancreatic cancer risk: an analysis from the International Pancreatic Cancer Case-Control Consortium. Ann Oncol. 2014; 25(10): 2065–2072.
  25. Gerstein HC, Bosch J, Dagenais GR, et al. ORIGIN Trial Investigators. Basal insulin and cardiovascular and other outcomes in dysglycemia. N Engl J Med. 2012; 367(4): 319–328.
  26. Molina-Montes E, Coscia C, Gómez-Rubio P, et al. PanGenEU Study Investigators. Deciphering the complex interplay between pancreatic cancer, diabetes mellitus subtypes and obesity/BMI through causal inference and mediation analyses. Gut. 2021; 70(2): 319–329.
  27. Wróbel MP, Marek B, Kajdaniuk D, et al. Metformin - a new old drug. Endokrynol Pol. 2017; 68(4): 482–496.
  28. Zhou J, Massey S, Story D, et al. Metformin: An Old Drug with New Applications. Int J Mol Sci. 2018; 19(10).
  29. Kułaczkowska ZM, Wróbel M, Rokicka D, et al. Metformin in patients with type 2 diabetes mellitus and heart failure: a review. Endokrynol Pol. 2021; 72(2): 163–170.
  30. Hotta N. A new perspective on the biguanide, metformin therapy in type 2 diabetes and lactic acidosis. J Diabetes Investig. 2019; 10(4): 906–908.
  31. Duca FA, Côté CD, Rasmussen BA, et al. Metformin activates a duodenal Ampk-dependent pathway to lower hepatic glucose production in rats. Nat Med. 2015; 21(5): 506–511.
  32. Rena G, Hardie DG, Pearson ER. The mechanisms of action of metformin. Diabetologia. 2017; 60(9): 1577–1585.
  33. Gong J, Robbins LA, Lugea A, et al. Diabetes, pancreatic cancer, and metformin therapy. Front Physiol. 2014; 5: 426.
  34. Muszyńska-Ogłaza A, Zarzycka-Lindner G, Olejniczak H, et al. Use of metformin is associated with lower incidence of cancer in patients with type 2 diabetes. Endokrynol Pol. 2017; 68(6): 652–658.
  35. Zhang K, Bai P, Dai H, et al. Metformin and risk of cancer among patients with type 2 diabetes mellitus: A systematic review and meta-analysis. Prim Care Diabetes. 2021; 15(1): 52–58.
  36. Terasaki F, Sugiura T, Okamura Y, et al. Oncological benefit of metformin in patients with pancreatic ductal adenocarcinoma and comorbid diabetes mellitus. Langenbecks Arch Surg. 2020; 405(3): 313–324.
  37. Oh TK, Song IA. Metformin Use and the Risk of Cancer in Patients with Diabetes: A Nationwide Sample Cohort Study. Cancer Prev Res (Phila). 2020; 13(2): 195–202.
  38. Dong YW, Shi YQ, He LW, et al. Effects of metformin on survival outcomes of pancreatic cancer: a meta-analysis. Oncotarget. 2017; 8(33): 55478–55488.
  39. Wei M, Liu Yu, Bi Y, et al. Metformin and pancreatic cancer survival: Real effect or immortal time bias? Int J Cancer. 2019; 145(7): 1822–1828.
  40. Dankner R, Roth J. More recent, better designed studies have weakened links between antidiabetes medications and cancer risk. Diabet Med. 2020; 37(2): 194–202.
  41. Drzewoski J, Hanefeld M. The Current and Potential Therapeutic Use of Metformin-The Good Old Drug. Pharmaceuticals (Basel). 2021; 14(2).
  42. Peric S, Stulnig TM. Diabetes and COVID-19 : Disease-Management-People. Wien Klin Wochenschr. 2020; 132(13-14): 356–361.
  43. Scheen AJ. Pharmacodynamics, efficacy and safety of sodium-glucose co-transporter type 2 (SGLT2) inhibitors for the treatment of type 2 diabetes mellitus. Drugs. 2015; 75(1): 33–59.
  44. Moses RG, Colagiuri S, Pollock C. SGLT2 inhibitors: New medicines for addressing unmet needs in type 2 diabetes. Australas Med J. 2014; 7(10): 405–415.
  45. Tang H, Yang K, Li X, et al. Pancreatic safety of sodium-glucose cotransporter 2 inhibitors in patients with type 2 diabetes mellitus: A systematic review and meta-analysis. Pharmacoepidemiol Drug Saf. 2020; 29(2): 161–172.
  46. Holst JJ. The incretin system in healthy humans: The role of GIP and GLP-1. Metabolism. 2019; 96: 46–55.
  47. Gallwitz B. Clinical Use of DPP-4 Inhibitors. Front Endocrinol (Lausanne). 2019; 10: 389.
  48. Zhang Z, Chen Xi, Lu P, et al. Incretin-based agents in type 2 diabetic patients at cardiovascular risk: compare the effect of GLP-1 agonists and DPP-4 inhibitors on cardiovascular and pancreatic outcomes. Cardiovasc Diabetol. 2017; 16(1): 31.
  49. Abd El Aziz M, Cahyadi O, Meier JJ, et al. Incretin-based glucose-lowering medications and the risk of acute pancreatitis and malignancies: a meta-analysis based on cardiovascular outcomes trials. Diabetes Obes Metab. 2020; 22(4): 699–704.
  50. Dicembrini I, Montereggi C, Nreu B, et al. Pancreatitis and pancreatic cancer in patientes treated with Dipeptidyl Peptidase-4 inhibitors: An extensive and updated meta-analysis of randomized controlled trials. Diabetes Res Clin Pract. 2020; 159: 107981.
  51. Almagthali AG, Alkhaldi EH, Alzahrani AS, et al. Dipeptidyl peptidase-4 inhibitors: Anti-diabetic drugs with potential effects on cancer. Diabetes Metab Syndr. 2019; 13(1): 36–39.
  52. Abdelmoneim AS, Hasenbank SE, Seubert JM, et al. Variations in tissue selectivity amongst insulin secretagogues: a systematic review. Diabetes Obes Metab. 2012; 14(2): 130–138.
  53. Khunti K, Chatterjee S, Gerstein H, et al. Do sulphonylureas still have a place in clinical practice? Lancet Diabetes Endocrinol. 2018; 6(10): 821–832.
  54. Stefansdottir G, Zoungas S, Chalmers J, et al. Intensive glucose control and risk of cancer in patients with type 2 diabetes. Diabetologia. 2011; 54(7): 1608–1614.
  55. Calip GS, Yu O, Elmore JG, et al. Comparative safety of diabetes medications and risk of incident invasive breast cancer: a population-based cohort study. Cancer Causes Control. 2016; 27(5): 709–720.
  56. Häggström C, Van Hemelrijck M, Zethelius B, et al. Prospective study of Type 2 diabetes mellitus, anti-diabetic drugs and risk of prostate cancer. Int J Cancer. 2017; 140(3): 611–617.
  57. Ye JH, Qian MH, Shi LZ, et al. Association Between Metformin and Sulfonylurea Monotherapies and Cancer Incidence: A Real-World Cohort Study in Shanghai, China. Diabetes Ther. 2019; 10(1): 245–258.
  58. Chaudhury A, Duvoor C, Reddy Dendi VS, et al. Clinical Review of Antidiabetic Drugs: Implications for Type 2 Diabetes Mellitus Management. Front Endocrinol (Lausanne). 2017; 8: 6.
  59. Li D, Yeung SCJ, Hassan MM, et al. Antidiabetic therapies affect risk of pancreatic cancer. Gastroenterology. 2009; 137(2): 482–488.
  60. Nanjan MJ, Mohammed M, Prashantha Kumar BR, et al. Thiazolidinediones as antidiabetic agents: A critical review. Bioorg Chem. 2018; 77: 548–567.
  61. Lebovitz HE. Thiazolidinediones: the Forgotten Diabetes Medications. Curr Diab Rep. 2019; 19(12): 151.
  62. Della-Morte D, Palmirotta R, Rehni AK, et al. Pharmacogenomics and pharmacogenetics of thiazolidinediones: role in diabetes and cardiovascular risk factors. Pharmacogenomics. 2014; 15(16): 2063–2082.
  63. Lewis JD, Habel LA, Quesenberry CP, et al. Pioglitazone Use and Risk of Bladder Cancer and Other Common Cancers in Persons With Diabetes. JAMA. 2015; 314(3): 265–277.
  64. Hedrington MS, Davis SN. Considerations when using alpha-glucosidase inhibitors in the treatment of type 2 diabetes. Expert Opin Pharmacother. 2019; 20(18): 2229–2235.
  65. Zhao Y, Wang Y, Lou H, et al. Alpha-glucosidase inhibitors and risk of cancer in patients with diabetes mellitus: a systematic review and meta-analysis. Oncotarget. 2017; 8(46): 81027–81039.

Regulations

Important: This website uses cookies. More >>

The cookies allow us to identify your computer and find out details about your last visit. They remembering whether you've visited the site before, so that you remain logged in - or to help us work out how many new website visitors we get each month. Most internet browsers accept cookies automatically, but you can change the settings of your browser to erase cookies or prevent automatic acceptance if you prefer.

Via MedicaWydawcą serwisu jest  "Via Medica sp. z o.o." sp.k., ul. Świętokrzyska 73, 80–180 Gdańsk

tel.:+48 58 320 94 94, faks:+48 58 320 94 60, e-mail:  viamedica@viamedica.pl