Lin CM, Huang HL, Chu FY, Fan HC, Chen HA, Chu DM, et al. Association between gastroenterological malignancy and diabetes mellitus and anti-diabetic therapy: a nationwide, population-based cohort study. PLoS ONE. 2015;10(5):1–11. https://doi.org/10.1371/journal.pone.0125421.

Article  CAS  Google Scholar 

Sung H, Ferlay J, Siegel RL, Laversanne M, Soerjomataram I, Jemal A, et al. Global Cancer Statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2021;71(3):209–49. https://doi.org/10.3322/caac.21660.

Article  PubMed  Google Scholar 

Pickhardt PJ, Pooler BD, Kim DH, Hassan C, Matkowskyj KA, Halberg RB. The natural history of colorectal polyps. Gastroenterol Clin North Am. 2018;47(3):515–36. https://doi.org/10.1016/j.gtc.2018.04.004.

Article  PubMed  PubMed Central  Google Scholar 

González N, Prieto I, Puerto-nevado L, Portal -S, Aguilera O, Gomez-guerrero C, et al. 2017 update on the relationship between diabetes and colorectal cancer : epidemiology , potential molecular mechanisms and therapeutic implications. 2017;8(11):18456–85. https://doi.org/10.18632/oncotarget.14472.

Cheng HC, Chang TK, Su WC, Tsai HL, Wang JY. Narrative review of the influence of diabetes mellitus and hyperglycemia on colorectal cancer risk and oncological outcomes. Transl Oncol. 2021;14(7): 101089. https://doi.org/10.1016/j.tranon.2021.101089.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Eddi R, Karki A, Shah A, Debari VA, Depasquale JR. Association of type 2 diabetes and colon adenomas. J Gastrointest Cancer. 2012;43(1):87–92. https://doi.org/10.1007/s12029-011-9316-7.

Article  CAS  PubMed  Google Scholar 

Huang HE, Yang YC, Wu JS, Wang RH, Lu FH, Chang CJ. The relationship between different glycemic statuses and colon polyps in a Taiwanese population. J Gastroenterol. 2014;49(7):1145–51. https://doi.org/10.1007/s00535-013-0863-5.

Article  CAS  PubMed  Google Scholar 

Vulcan A, Manjer J, Ohlsson B. High blood glucose levels are associated with higher risk of colon cancer in men: a cohort study. BMC Cancer. 2017;17(1):1–8. https://doi.org/10.1186/s12885-017-3874-4.

Article  CAS  Google Scholar 

Vasconcelos-Dos-Santos A, Loponte HFBR, Mantuano NR, Oliveira IA, De Paula IF, Teixeira LK, et al. Hyperglycemia exacerbates colon cancer malignancy through hexosamine biosynthetic pathway. Oncogenesis. 2017;6(3). https://doi.org/10.1038/oncsis.2017.2.

Sandhu MS, Dunger DB, Giovannucci EL. Insulin, insulin-like growth factor-I (IGF-I), IGF binding proteins, their biologic interactions, and colorectal cancer. J Natl Cancer Inst. 2002;94(13). https://doi.org/10.1093/jnci/94.13.972.

Yoshida I, Suzuki A, Vallée M, Matano Y, Masunaga T, Zenda T, et al. Serum insulin levels and the prevalence of adenomatous and hyperplastic polyps in the proximal colon. Clin Gastroenterol Hepatol. 2006;4(10):1225–31. https://doi.org/10.1016/j.cgh.2006.07.002.

Article  CAS  PubMed  Google Scholar 

Heer E, Ruan Y, Mah B, Nguyen T, Lyons H, Poirier A, et al. The efficacy of chemopreventive agents on the incidence of colorectal adenomas: a systematic review and network meta-analysis. Prev Med. 2022;9(162): 107169. https://doi.org/10.1016/j.ypmed.2022.107169.

Article  Google Scholar 

Ng CAW, Jiang AA, Toh EMS, Ng CH, Ong ZH, Peng S, et al. Metformin and colorectal cancer: a systematic review, meta-analysis and meta-regression. Int J Colorectal Dis. 2020;35(8):1501–12. https://doi.org/10.1007/s00384-020-03676-x.

Article  PubMed  Google Scholar 

Lee JW, Choi EA, Kim YS, Kim Y, You HS, Han YE, et al. Metformin usage and the risk of colorectal cancer: a national cohort study. Int J Colorectal Dis. 2021;36(2):303–10. https://doi.org/10.1007/s00384-020-03765-x.

Bahardoust M, Mousavi S, Moezi ZD, Yarali M, Tayebi A, Olamaeian F, et al. Effect of metformin use on survival and recurrence rate of gastric cancer after gastrectomy in diabetic patients: a systematic review and meta-analysis of observational studies. J Gastrointest Cancer. 2023. https://doi.org/10.1007/s12029-023-00955-y.

Article  PubMed  Google Scholar 

Hu J, Fan HD, Gong JP, Mao QS. The relationship between the use of metformin and the risk of pancreatic cancer in patients with diabetes: a systematic review and meta-analysis. BMC Gastroenterol. 2023;23(1):1–21. https://doi.org/10.1186/s12876-023-02671-0.

Article  CAS  Google Scholar 

Berkovic MC, Mikulic D, Bilic-Curcic I, Mrzljak A. How far along are we in revealing the connection between metformin and colorectal cancer? World J Gastroenterol. 2021;27(14):1362–8. https://doi.org/10.3748/wjg.v27.i14.1362.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Boutaud M, Auger C, Verdier M, Christou N. Metformin treatment reduces CRC aggressiveness in a glucose-independent manner: an in vitro and ex vivo study. Cancers (Basel). 2023;15(14):1–21. https://doi.org/10.3390/cancers15143724.

Article  CAS  Google Scholar 

Fernández-Fernández FJ. Antineoplastic potential of metformin in colorectal cancer. Eur J Intern Med. 2017;37(8): e22. https://doi.org/10.1016/j.ejim.2016.08.034.

Article  CAS  PubMed  Google Scholar 

Deng M, Lei S, Huang D, Wang H, Xia S, Xu E, et al. Suppressive effects of metformin on colorectal adenoma incidence and malignant progression. Pathol Res Pract. 2020;216(2): 152775. https://doi.org/10.1016/j.prp.2019.152775.

Article  CAS  PubMed  Google Scholar 

Bradley MC, Ferrara A, Achacoso N, Ehrlich SF, Quesenberry CP, Habel LA. A cohort study of metformin and colorectal cancer risk among patients with diabetes mellitus. Cancer Epidemiol Biomarkers Prev. 2018;27(5):525–30. https://doi.org/10.1158/1055-9965.EPI-17-0424.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Cho YH, Ko BM, Kim SH, Myung YS, Choi JH, Han JP, et al. Does metformin affect the incidence of colonic polyps and adenomas in patients with type 2 diabetes mellitus? Intest Res. 2014;12(2):139. https://doi.org/10.5217/ir.2014.12.2.139.

Article  PubMed  PubMed Central  Google Scholar 

Shin CM, Kim N, Han K, Kim B, Jung JH, Oh TJ, et al. Anti-diabetic medications and the risk for colorectal cancer: a population-based nested case-control study. Cancer Epidemiol. 2020;64. Available from: https://doi.org/10.1016/j.canep.2019.101658.

Erkinantti S, Marttila M, Sund R, Arffman M, Urpilainen E, Puistola U, et al. Association of metformin, other antidiabetic medications, and statins with incidence of colon cancer in patients with type 2 diabetes. Clin Colorectal Cancer. 2021;20(2):e113–9. https://doi.org/10.1016/j.clcc.2020.11.003.

Article  PubMed  Google Scholar 

Moghaddam AA, Woodward M, Huxley R. Obesity and risk of colorectal cancer: a meta-analysis of 31 studies with 70,000 events. Cancer Epidemiol Biomarkers Prev. 2007;16(12):2533–47. https://doi.org/10.1158/1055-9965.EPI-07-0708.

Article  PubMed  Google Scholar 

Lai EJ, Calderwood AH, Doros G, Fix OK, Jacobson BC. The Boston Bowel Preparation Scale: a valid and reliable instrument for colonoscopy-oriented research. Gastrointest Endosc. 2009;69(3 Pt 2):620–5. https://doi.org/10.1016/j.gie.2008.05.057.

Article  PubMed  PubMed Central  Google Scholar 

Hassan C, Antonelli G, Dumonceau J, Regula J, Bretthauer M, Chaussade S, et al. Post-polypectomy colonoscopy surveillance: European Society of Gastrointestinal Endoscopy (ESGE) Guideline – Update 2020. Endoscopy. 2020;52:717–29. https://doi.org/10.1055/a-1185-3109.

Article  Google Scholar 

See S, Care D, Suppl SS. 9. Pharmacologic approaches to glycemic treatment: standards of medical care in diabetes-2020. Diabetes Care. 2020;43(1):S98–110. https://doi.org/10.2337/dc20-S009.

McCracken E, Monaghan M, Sreenivasan S. Pathophysiology of the metabolic syndrome. Clin Dermatol. 2018;36(1):14–20. https://doi.org/10.1016/j.clindermatol.2017.09.004.

Article  PubMed  Google Scholar 

Weykamp C. HbA1c: A review of analytical and clinical aspects. Ann Lab Med. 2013;33(6):393–400. https://doi.org/10.3343/alm.2013.33.6.393.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Rokkas T, Portincasa P. Colon neoplasia in patients with type 2 diabetes on metformin: a meta-analysis. Eur J Intern Med. 2016;33:60–6. https://doi.org/10.1016/j.ejim.2016.05.027.

Article  CAS  PubMed  Google Scholar 

Higurashi T, Hosono K, Takahashi H, Komiya Y, Umezawa S, Sakai E, et al. Metformin for chemoprevention of metachronous colorectal adenoma or polyps in post-polypectomy patients without diabetes: a multicentre double-blind, placebo-controlled, randomised phase 3 trial. Lancet Oncol. 2016;17(4):475–83. https://doi.org/10.1016/S1470-2045(15)00565-3.

Article  CAS  PubMed  Google Scholar 

Mansourian M, Karimi R, Vaseghi G. Different effects of metformin and insulin on primary and secondary chemoprevention of colorectal adenoma in diabetes type 2: Traditional and Bayesian meta-analysis. EXCLI J. 2018;17:45–56. https://doi.org/10.17179/excli2017-993.

Krigel A, Nguyen S, Talukder N, Huang C, Buitrago C, Karkenny G, et al. Metformin use is inversely associated with prevalent, but not incident colorectal adenomas. Dig Dis Sci. 2022;67(10):4886–94. https://doi.org/10.1007/s10620-021-07336-0.

Article  CAS  PubMed  Google Scholar 

Park JJ, Kim BC, Hong SP, Seo Y, Lee HS, Park YS, et al. The effect of metformin in treatment of adenomas in patients with familial adenomatous polyposis. Cancer Prev Res. 2021;14(5):563–72. https://doi.org/10.1158/1940-6207.CAPR-20-0580.

Article  CAS  Google Scholar 

Chang YT, Tsai HL, Kung YT, Yeh YS, Huang CW, Ma CJ, et al. Dose-dependent relationship between metformin and colorectal cancer occurrence among patients with type 2 diabetes—a nationwide cohort study. Transl Oncol. 2018;11(2):535–41. https://doi.org/10.1016/j.tranon.2018.02.012.

Article  PubMed  PubMed Central  Google Scholar 

Zhang H, Yang Y, Lee S, Park S, Nam C, Jee S. Metformin use is not associated with colorectal cancer incidence in type-2 diabetes patients: evidence from methods that avoid immortal time bias. Int J Color Dis. 2022;37(8):1827–34. https://doi.org/10.1007/s00384-022-04212-9.

Article  Google Scholar 

White A, Ironmonger L, Steele RJC, Ormiston-Smith N, Crawford C, Seims A. A review of sex-related differences in colorectal cancer incidence, screening uptake, routes to diagnosis, cancer stage and survival in the UK. BMC Cancer. 2018;18(1):1–11. https://doi.org/10.1186/s12885-018-4786-7%0ARESEARCH.

Article  Google Scholar 

Kanadiya MK, Gohel TD, Sanaka MR, Thota PN, Shubrook JH. Relationship between type-2 diabetes and use of metformin with risk of colorectal adenoma in an American population receiving colonoscopy. J Diabetes Complications. 2013;27(5):463–6. https://doi.org/10.1016/j.jdiacomp.