Skip to main content
Top
Published in: Gastric Cancer 6/2020

01-11-2020 | Metformin | Original Article

Metformin use reduced the risk of stomach cancer in diabetic patients in Korea: an analysis of Korean NHIS-HEALS database

Authors: Joungyoun Kim, Hyeong-Jin Hyun, Eun-A. Choi, Yonghwan Kim, Yoon-Jong Bae, Hee-Taik Kang

Published in: Gastric Cancer | Issue 6/2020

Login to get access

Abstract

Background

Diabetes mellitus (DM) increases atherosclerotic cardiovascular complications and cancer risks. Stomach cancer is the most common cancer in Korea. Although the survival rate of stomach cancer has improved, the disease burden is still high.

Methods

This retrospective study investigated the association between metformin use and stomach cancer incidence in a Korean population using the National Health Insurance Service-National Health Screening Cohort database. Participants aged 40–80 years old at the baseline period (2002–2003) were enrolled. The study population was categorized into three groups of metformin non-users with DM, metformin users with DM, and individuals without DM (No DM group).

Results

A total of 347,895 participants (14,922 metformin non-users, 9891 metformin users, and 323,082 individuals without DM) were included in the final analysis. The median follow-up duration was 12.70 years. The estimated cumulative incidence of stomach cancer was highest in metformin non-users and lowest in the No DM group (men vs. women: 3.75 vs. 1.97% in metformin non-users, 2.91 vs. 1.53% in metformin users, and 2.54 vs. 0.95% in the No DM group). Compared with metformin non-users, the hazard ratios (95% confidence intervals) for stomach cancer incidence of metformin users and the No DM group were 0.710 (0.579–0.870) and 0.879 (0.767–1.006) in men and 0.700 (0.499–0.981) and 0.701 (0.544–0.903) in women, respectively, after full adjustment.

Conclusions

Metformin users with DM in the Korean population were at lower risk of stomach cancer incidence after controlling for potential confounding factors.
Appendix
Available only for authorised users
Literature
1.
go back to reference Jung KW, Won YJ, Kong HJ, Lee ES. Cancer statistics in korea: incidence, mortality, survival, and prevalence in 2016. Cancer Res Treat. 2019;51:417–30.CrossRef Jung KW, Won YJ, Kong HJ, Lee ES. Cancer statistics in korea: incidence, mortality, survival, and prevalence in 2016. Cancer Res Treat. 2019;51:417–30.CrossRef
2.
go back to reference Cho NH, Shaw JE, Karuranga S, Huang Y, da Rocha FJ, Ohlrogge A, et al. IDF diabetes atlas: global estimates of diabetes prevalence for 2017 and projections for 2045. Diabetes Res Clin Prac. 2018;138:271–81.CrossRef Cho NH, Shaw JE, Karuranga S, Huang Y, da Rocha FJ, Ohlrogge A, et al. IDF diabetes atlas: global estimates of diabetes prevalence for 2017 and projections for 2045. Diabetes Res Clin Prac. 2018;138:271–81.CrossRef
3.
go back to reference Lee Jw, Kang HT, Lim HJ, Park B. Trends in diabetes prevalence among Korean adults based on Korean National Health and Nutrition Examination Surveys III–VI. Diabetes Res Clin Prac. 2018;138:57–655.CrossRef Lee Jw, Kang HT, Lim HJ, Park B. Trends in diabetes prevalence among Korean adults based on Korean National Health and Nutrition Examination Surveys III–VI. Diabetes Res Clin Prac. 2018;138:57–655.CrossRef
4.
go back to reference American Diabetes Association. 9 Pharmacologic approaches to glycemic treatment: standards of medical care in diabetes. Diabetes Care. 2019;42:S90–S102.CrossRef American Diabetes Association. 9 Pharmacologic approaches to glycemic treatment: standards of medical care in diabetes. Diabetes Care. 2019;42:S90–S102.CrossRef
5.
go back to reference Davies MJ, D'Alessio DA, Fradkin J, Kernan WN, Mathieu C, Mingrone G, et al. Management of hyperglycaemia in type 2 diabetes 2018. A consensus report by the American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD). Diabetologia. 2018;2019(61):2461–98.CrossRef Davies MJ, D'Alessio DA, Fradkin J, Kernan WN, Mathieu C, Mingrone G, et al. Management of hyperglycaemia in type 2 diabetes 2018. A consensus report by the American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD). Diabetologia. 2018;2019(61):2461–98.CrossRef
6.
go back to reference Rena G, Hardie DG, Pearson ER. The mechanisms of action of metformin. Diabetologia. 2017;60:1577–85.CrossRef Rena G, Hardie DG, Pearson ER. The mechanisms of action of metformin. Diabetologia. 2017;60:1577–85.CrossRef
7.
go back to reference Pernicova I, Korbonits M. Metformin—mode of action and clinical implications for diabetes and cancer. Nat Rev Endocrinol. 2014;10:143–56.CrossRef Pernicova I, Korbonits M. Metformin—mode of action and clinical implications for diabetes and cancer. Nat Rev Endocrinol. 2014;10:143–56.CrossRef
8.
go back to reference Seong SC, Kim YY, Park SK, Khang YH, Kim HC, Park JH, et al. Cohort profile: the national health insurance service-national health screening cohort (NHIS-HEALS) in Korea. BMJ open. 2017;7:e016640.CrossRef Seong SC, Kim YY, Park SK, Khang YH, Kim HC, Park JH, et al. Cohort profile: the national health insurance service-national health screening cohort (NHIS-HEALS) in Korea. BMJ open. 2017;7:e016640.CrossRef
9.
go back to reference García-Jiménez C, Gutiérrez-Salmerón M, Chocarro-Calvo A, García-Martinez JM, Castaño A, De la Vieja A. From obesity to diabetes and cancer: epidemiological links and role of therapies. Br J cancer. 2016;114:716–22.CrossRef García-Jiménez C, Gutiérrez-Salmerón M, Chocarro-Calvo A, García-Martinez JM, Castaño A, De la Vieja A. From obesity to diabetes and cancer: epidemiological links and role of therapies. Br J cancer. 2016;114:716–22.CrossRef
10.
go back to reference UK Prospective Diabetes Study (UKPDS) Group. Effect of intensive blood-glucose control with metformin on complications in overweight patients with type 2 diabetes (UKPDS 34). Lancet. 1998;352:854–65.CrossRef UK Prospective Diabetes Study (UKPDS) Group. Effect of intensive blood-glucose control with metformin on complications in overweight patients with type 2 diabetes (UKPDS 34). Lancet. 1998;352:854–65.CrossRef
11.
go back to reference Madiraju AK, Erion DM, Rahimi Y, Zhang XM, Braddock DT, Albright RA, et al. Metformin suppresses gluconeogenesis by inhibiting mitochondrial glycerophosphate dehydrogenase. Nature. 2014;510:542–6.CrossRef Madiraju AK, Erion DM, Rahimi Y, Zhang XM, Braddock DT, Albright RA, et al. Metformin suppresses gluconeogenesis by inhibiting mitochondrial glycerophosphate dehydrogenase. Nature. 2014;510:542–6.CrossRef
12.
go back to reference Mclntyre HD, Ma A, Bird DM, Paterson CA, Ravenscroft PJ, Cameron DP. Metformin increases insulin sensitivity and basal glucose clearance in type 2 (non-insulin dependent) diabetes mellitus. Aust N Z J Med. 1991;21:714–9.CrossRef Mclntyre HD, Ma A, Bird DM, Paterson CA, Ravenscroft PJ, Cameron DP. Metformin increases insulin sensitivity and basal glucose clearance in type 2 (non-insulin dependent) diabetes mellitus. Aust N Z J Med. 1991;21:714–9.CrossRef
13.
go back to reference Viollet B, Guigas B, Sanz Garcia N, Leclerc J, Foretz M, Andreelli F. Cellular and molecular mechanisms of metformin: an overview. Clin Sci (Lond). 2012;122:253–70.CrossRef Viollet B, Guigas B, Sanz Garcia N, Leclerc J, Foretz M, Andreelli F. Cellular and molecular mechanisms of metformin: an overview. Clin Sci (Lond). 2012;122:253–70.CrossRef
14.
go back to reference Bridges HR, Jones AJ, Pollak MN, Hirst J. Effects of metformin and other biguanides on oxidative phosphorylation in mitochondria. Biochem J. 2014;462:475–87.CrossRef Bridges HR, Jones AJ, Pollak MN, Hirst J. Effects of metformin and other biguanides on oxidative phosphorylation in mitochondria. Biochem J. 2014;462:475–87.CrossRef
15.
go back to reference Owen MR, Doran E, Halestrap AP. Evidence that metformin exerts its anti-diabetic effects through inhibition of complex 1 of the mitochondrial respiratory chain. Biochem J. 2000;348:607–14.CrossRef Owen MR, Doran E, Halestrap AP. Evidence that metformin exerts its anti-diabetic effects through inhibition of complex 1 of the mitochondrial respiratory chain. Biochem J. 2000;348:607–14.CrossRef
16.
go back to reference Hardie DG, Ross FA, Hawley SA. AMP-activated protein kinase: a target for drugs both ancient and modern. Chem Biol. 2012;19:1222–366.CrossRef Hardie DG, Ross FA, Hawley SA. AMP-activated protein kinase: a target for drugs both ancient and modern. Chem Biol. 2012;19:1222–366.CrossRef
17.
go back to reference Jeon SM. Regulation and function of AMPK in physiology and diseases. Exp Mol Med. 2016;48:e245.CrossRef Jeon SM. Regulation and function of AMPK in physiology and diseases. Exp Mol Med. 2016;48:e245.CrossRef
18.
go back to reference Kim YI, Kim SY, Cho SJ, Park JH, Choi IJ, Lee YJ, et al. Long-term metformin use reduces gastric cancer risk in type 2 diabetics without insulin treatment: a nationwide cohort study. Aliment Pharmacol Ther. 2014;39:854–63.CrossRef Kim YI, Kim SY, Cho SJ, Park JH, Choi IJ, Lee YJ, et al. Long-term metformin use reduces gastric cancer risk in type 2 diabetics without insulin treatment: a nationwide cohort study. Aliment Pharmacol Ther. 2014;39:854–63.CrossRef
19.
go back to reference Ruiter R, Visser LE, van Herk-Sukel MP, Coebergh JW, Haak HR, Geelhoed-Duijvestijn PH, et al. Lower risk of cancer in patients on metformin in comparison with those on sulfonylurea derivatives: results from a large population-based follow-up study. Diabetes Care. 2012;35:119–24.CrossRef Ruiter R, Visser LE, van Herk-Sukel MP, Coebergh JW, Haak HR, Geelhoed-Duijvestijn PH, et al. Lower risk of cancer in patients on metformin in comparison with those on sulfonylurea derivatives: results from a large population-based follow-up study. Diabetes Care. 2012;35:119–24.CrossRef
20.
go back to reference Lee MS, Hsu CC, Wahlqvist ML, Tsai HN, Chang YH, Huang YC. Type 2 diabetes increases and metformin reduces total, colorectal, liver and pancreatic cancer incidences in Taiwanese: a representative population prospective cohort study of 800,000 individuals. BMC cancer. 2011;11:20.CrossRef Lee MS, Hsu CC, Wahlqvist ML, Tsai HN, Chang YH, Huang YC. Type 2 diabetes increases and metformin reduces total, colorectal, liver and pancreatic cancer incidences in Taiwanese: a representative population prospective cohort study of 800,000 individuals. BMC cancer. 2011;11:20.CrossRef
21.
go back to reference Zhou XL, Xue WH, Ding XF, Li LF, Dou MM, Zhang WJ, et al. Association between metformin and the risk of gastric cancer in patients with type 2 diabetes mellitus: a meta-analysis of cohort studies. Oncotarget. 2017;8:55622–31.CrossRef Zhou XL, Xue WH, Ding XF, Li LF, Dou MM, Zhang WJ, et al. Association between metformin and the risk of gastric cancer in patients with type 2 diabetes mellitus: a meta-analysis of cohort studies. Oncotarget. 2017;8:55622–31.CrossRef
22.
go back to reference Li P, Zhang C, Gao P, Chen X, Ma B, Yu D, et al. Metformin use and its effect on gastric cancer in patients with type 2 diabetes: a systematic review of observational studies. Oncol Lett. 2018;15:1191–9.PubMed Li P, Zhang C, Gao P, Chen X, Ma B, Yu D, et al. Metformin use and its effect on gastric cancer in patients with type 2 diabetes: a systematic review of observational studies. Oncol Lett. 2018;15:1191–9.PubMed
23.
go back to reference Tseng CH. Metformin reduces gastric cancer risk in patients with type 2 diabetes mellitus. Aging (Albany NY). 2016;8:1636–49.CrossRef Tseng CH. Metformin reduces gastric cancer risk in patients with type 2 diabetes mellitus. Aging (Albany NY). 2016;8:1636–49.CrossRef
Metadata
Title
Metformin use reduced the risk of stomach cancer in diabetic patients in Korea: an analysis of Korean NHIS-HEALS database
Authors
Joungyoun Kim
Hyeong-Jin Hyun
Eun-A. Choi
Yonghwan Kim
Yoon-Jong Bae
Hee-Taik Kang
Publication date
01-11-2020
Publisher
Springer Singapore
Published in
Gastric Cancer / Issue 6/2020
Print ISSN: 1436-3291
Electronic ISSN: 1436-3305
DOI
https://doi.org/10.1007/s10120-020-01085-1

Other articles of this Issue 6/2020

Gastric Cancer 6/2020 Go to the issue