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Clinical and Translational Oncology
Published in: Clinical and Translational Oncology 9/2020

01-09-2020 | Metformin | Research Article

The effect of metformin on gastric cancer in patients with type 2 diabetes: a systematic review and meta-analysis

Authors: Y. Shuai, C. Li, X. Zhou

Published in: Clinical and Translational Oncology | Issue 9/2020

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Abstract

Background

Metformin, a drug widely used in the treatment of diabetes, has proven preventive and survival benefits for various malignancies. However, the effect of metformin on gastric cancer risk and survival rate in T2DM patients remains controversial. Therefore, we conducted a systematic review and meta-analysis to evaluate the effect of metformin on gastric cancer in T2DM patients.

Methods

We searched PubMed, EMBASE, Medline and the Cochrane Library for related studies up to October 22, 2019. Pooled hazard ratios with 95% confidence intervals were calculated using random-effects model. Heterogeneity was assessed. All articles were evaluated by Newcastle–Ottawa Scale.

Results

A total of 11 cohort studies met eligibility criteria and were included in the meta-analysis. The use of metformin was related to a significant 21% reduction in GC incidence (HR 0.790; 95% CI 0.624–1.001). Subgroup analysis showed that the use of metformin significantly reduced the risk of gastric cancer in T2DM patients in Asian populations, but not in western populations. In a pooled analysis of 3 studies, metformin use was associated with increased overall survival rate (HR 0.817; 95% CI 0.600–1.113) and cancer-specific survival rate (HR 0.824; 95% CI 0.614–1.106) of T2DM patients.

Conclusions

Metformin could reduce the risk of gastric cancer in T2DM patients, particularly in Asian populations. However, it is debatable whether metformin use can improve the prognosis of gastric cancer in T2DM patients.
Literature
1.
Fock KM. Review article: the epidemiology and prevention of gastric cancer. Aliment Pharmacol Ther. 2014;40(3):250–60.PubMedCrossRef
2.
Ajani JA, D’Amico TA, Almhanna K, Bentrem DJ, Chao J, Das P, et al. Gastric cancer, version 3.2016, NCCN clinical practice guidelines in oncology. J Natl Compr Canc Netw. 2016;14(10):1286–312.PubMedCrossRef
3.
Wild S, Roglic G, Green A, Sicree R, King H. Global prevalence of diabetes: estimates for the year 2000 and projections for 2030. Diabetes Care. 2004;27(5):1047–53.PubMedCrossRef
4.
Adami HO, McLaughlin J, Ekbom A, Berne C, Silverman D, Hacker D, et al. Cancer risk in patients with diabetes mellitus. Cancer Causes Control. 1991;2(5):307–14.PubMedCrossRef
5.
La Vecchia C, Negri E, Franceschi S, D’Avanzo B, Boyle P. A case-control study of diabetes mellitus and cancer risk. Br J Cancer. 1994;70(5):950–3.PubMedPubMedCentralCrossRef
6.
Giovannucci E, Harlan DM, Archer MC, Bergenstal RM, Gapstur SM, Habel LA, et al. Diabetes and cancer: a consensus report. Diabetes Care. 2010;33(7):1674–85.PubMedPubMedCentralCrossRef
7.
Coughlin SS, Calle EE, Teras LR, Petrelli J, Thun MJ. Diabetes mellitus as a predictor of cancer mortality in a large cohort of US adults. Am J Epidemiol. 2004;159(12):1160–7.PubMedCrossRef
8.
Rousseau MC, Parent ME, Pollak MN, Siemiatycki J. Diabetes mellitus and cancer risk in a population-based case-control study among men from Montreal Canada. Int J Cancer. 2006;118(8):2105–9.PubMedCrossRef
9.
Inoue M, Iwasaki M, Otani T, Sasazuki S, Noda M, Tsugane S, et al. Diabetes mellitus and the risk of cancer: results from a large-scale population-based cohort study in Japan. Arch Intern Med. 2006;166(17):1871–7.PubMedCrossRef
10.
Yin M, Zhou J, Gorak EJ, Quddus F. Metformin is associated with survival benefit in cancer patients with concurrent type 2 diabetes: a systematic review and meta-analysis. Oncologist. 2013;18(12):1248–55.PubMedPubMedCentralCrossRef
11.
He XK, Su TT, Si JM, Sun LM. Metformin is associated with slightly reduced risk of colorectal cancer and moderate survival benefits in diabetes mellitus: a meta-analysis. Med (Baltimore). 2016;95(7):e2749.CrossRef
12.
Stopsack KH, Ziehr DR, Rider JR, Giovannucci EL. Metformin and prostate cancer mortality: a meta-analysis. Cancer Causes Control. 2016;27(1):105–13.PubMedCrossRef
13.
Xu H, Chen K, Jia X, Tian Y, Dai Y, Li D, et al. Metformin use is associated with better survival of breast cancer patients with diabetes: a meta-analysis. Oncologist. 2015;20(11):1236–44.PubMedPubMedCentralCrossRef
14.
Wan G, Yu X, Chen P, Wang X, Pan D, Wang X, et al. Metformin therapy associated with survival benefit in lung cancer patients with diabetes. Oncotarget. 2016;7(23):35437–45.PubMedPubMedCentralCrossRef
15.
Lee CK, Jung M, Jung I, Heo SJ, Jeong YH, An JY, et al. Cumulative metformin use and its impact on survival in gastric cancer patients after gastrectomy. Ann Surg. 2016;263(1):96–102.PubMedCrossRef
16.
Kato K, Gong J, Iwama H, Kitanaka A, Tani J, Miyoshi H, et al. The antidiabetic drug metformin inhibits gastric cancer cell proliferation in vitro and in vivo. Mol Cancer Ther. 2012;11(3):549–60.PubMedCrossRef
17.
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(33):55622–31.PubMedPubMedCentralCrossRef
18.
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(1):1191–9.PubMed
19.
Dulskas A, Patasius A, Linkeviciute-Ulinskiene D, Zabuliene L, Smailyte G. A cohort study of antihyperglycemic medication exposure and survival in patients with gastric cancer. Aging (Albany NY). 2019;11(17):7197–205.CrossRef
20.
Valent F. Diabetes mellitus and cancer of the digestive organs: an Italian population-based cohort study. J Diabetes Complicat. 2015;29(8):1056–61.CrossRef
21.
Decensi A, Puntoni M, Goodwin P, Cazzaniga M, Gennari A. Metformin and cancer risk in diabetic patients: a systematic review and meta-analysis. Cancer Prev Res (Phila). 2010;3(11):1451–61.CrossRef
22.
Stang A. Critical evaluation of the Newcastle–Ottawa scale for the assessment of the quality of nonrandomized studies in meta-analyses. Eur J Epidemiol. 2010;25(9):603–5.PubMedCrossRef
23.
24.
25.
26.
Duval S, Tweedie R. Trim and fill: a simple funnel-plot-based method of testing and adjusting for publication bias in meta-analysis. Biometrics. 2000;56(2):455–63.PubMedCrossRef
27.
Rothstein HR, Sutton AJ, Borenstein M. Publication bias in meta-analysis: prevention, assessment and adjustments. Psychometrika. 2007;72(2):269.CrossRef
28.
Chen YL, Cheng KC, Lai SW, Tsai IJ, Lin CC, Sung FC, et al. Diabetes and risk of subsequent gastric cancer: a population-based cohort study in Taiwan. Gastric Cancer. 2013;16(3):389–96.PubMedCrossRef
29.
Lee MS, Hsu CC, Wahlqvist ML, Tsai HN, Chang YH, Huang YC, et al. 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.PubMedPubMedCentralCrossRef
30.
Tseng CH. Metformin reduces gastric cancer risk in patients with type 2 diabetes mellitus. Aging (Albany NY). 2016;8(8):1636–49.CrossRef
31.
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(1):119–24.PubMedCrossRef
32.
De Jong RG, Burden AM, de Kort S, van Herk-Sukel MP, Vissers PA, Janssen PK, et al. No decreased risk of gastrointestinal cancers in users of metformin in The Netherlands; a time-varying analysis of metformin exposure. Cancer Prev Res (Phila). 2017;10(5):290–7.CrossRef
33.
Baglia ML, Cui Y, Zheng T, Yang G, Li H, You M, et al. Diabetes medication use in association with survival among patients of breast, colorectal, lung, and gastric cancer. Cancer Res Treat. 2019;51(2):538–46.PubMedCrossRef
34.
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(8):854–63.PubMedCrossRef
35.
Tsilidis KK, Capothanassi D, Allen NE, Rizos EC, Lopez DS, van Veldhoven K, et al. Metformin does not affect cancer risk: a cohort study in the U.K. clinical practice research datalink analyzed like an intention-to-treat trial. Diabetes Care. 2014;37(9):2522–32.PubMedCrossRef
36.
Cheung KS, Chan EW, Wong AYS, Chen L, Seto WK, Wong ICK, et al. Metformin use and gastric cancer risk in diabetic patients after helicobacter pylori eradication. J Natl Cancer Inst. 2019;111(5):484–9.PubMedCrossRef
37.
Murff HJ, Roumie CL, Greevy RA, Hackstadt AJ, McGowan LED, Hung AM, et al. Metformin use and incidence cancer risk: evidence for a selective protective effect against liver cancer. Cancer Causes Control. 2018;29(9):823–32.PubMedPubMedCentralCrossRef
38.
Zheng J, Xie SH, Santoni G, Lagergren J. Metformin use and risk of gastric adenocarcinoma in a Swedish population-based cohort study. Br J Cancer. 2019;121(10):877–82.PubMedPubMedCentralCrossRef
39.
40.
Pollak M. Insulin and insulin-like growth factor signalling in neoplasia. Nat Rev Cancer. 2008;8(12):915–28.PubMedCrossRef
41.
Jalving M, Gietema JA, Lefrandt JD, de Jong S, Reyners AK. Metformin: Taking away the candy for cancer? Eur J Cancer. 2010;46(13):2369–80.PubMedCrossRef
42.
43.
Han G, Gong H, Wang Y, Guo S, Liu K. AMPK/mTOR-mediated inhibition of survivin partly contributes to metformin-induced apoptosis in human gastric cancer cell. Cancer Biol Ther. 2015;16(1):77–87.PubMedCrossRef
44.
Choi SI, Yoon C, Park MR, Lee D, Kook MC, Lin JX, et al. CDX1 expression induced by CagA-expressing helicobacter pylori promotes gastric tumorigenesis. Mol Cancer Res. 2019;17(11):2169–83.PubMedCrossRef
45.
Home PD, Kahn SE, Jones NP, Noronha D, Beck-Nielsen H, Viberti G, et al. Experience of malignancies with oral glucose-lowering drugs in the randomized controlled ADOPT (A Diabetes Outcome Progression Trial) and RECORD (Rosiglitazone Evaluated for Cardiovascular Outcomes and Regulation of Glycaemia in Diabetes) clinical trials. Diabetologia. 2010;53(9):1838–45.PubMedPubMedCentralCrossRef
46.
Lacroix O, Couttenier A, Vaes E, Cardwell CR, De Schutter H, Robert A, et al. Impact of metformin on gastric adenocarcinoma survival: a Belgian population-based study. Cancer Epidemiol. 2018;53:149–55.PubMedCrossRef
47.
Ikeda F, Doi Y, Yonemoto K, Ninomiya T, Kubo M, Shikata K, et al. Hyperglycemia increases risk of gastric cancer posed by Helicobacter pylori infection: a population-based cohort study. Gastroenterology. 2009;136(4):1234–41.PubMedCrossRef
48.
Metadata
Title
The effect of metformin on gastric cancer in patients with type 2 diabetes: a systematic review and meta-analysis
Authors
Y. Shuai
C. Li
X. Zhou
Publication date
01-09-2020
Publisher
Springer International Publishing
Published in
Clinical and Translational Oncology / Issue 9/2020
Print ISSN: 1699-048X
Electronic ISSN: 1699-3055
DOI
https://doi.org/10.1007/s12094-020-02304-y

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