Preventative and Therapeutic Effects of Metformin in Gastric Cancer: A New Contribution of an Old Friend

Figures & data

Table 1 Characteristics of Studies on Metformin and Gastric Cancer Risk

Author (Year)	Population	District	Groups	No. of Patients	Results for Metformin Users
Lee (2011)^Citation14	DM	Taiwan	Metformin; non-metformin	15,717 (4,327/11,390)	No impact on GC risk
Ruiter (2012)^Citation15	DM using metformin or sulfonylurea	Netherland	Metformin; sulfonylurea	85,289 52,698/32,591	Reduced GC risk
Kim (2014)^Citation16	T2DM, insulin non-users	Republic of Korea	Metformin; non-metformin	32,978 (26,690/6,288)	Reduced GC risk
Murff (2014)^Citation17	DM using metformin or sulfonylurea	U. S.	Metformin; sulfonylurea	84,434 (42,217/42,217)	No impact on GC risk
Tsilidis (2014)^Citation18	DM using metformin or sulfonylurea	U. K.	Metformin; sulfonylurea	69,748 (51,484/18,264)	No impact on GC risk
Valent (2015)^Citation19	T2DM	Italy	Metformin; non-metformin	138,521 (63,119/75,402)	Reduced GC risk
Tseng (2016)^Citation20	T2DM	China	Metformin; non-metformin	304,188 (287,971/16,217)	Reduced GC risk
De Jong (2017)^Citation21	DM using ≥1 non-insulin antidiabetic drug (NIAD)	Netherland	Metformin; other NIADs	57,114 (37,215/19,899)	No impact on GC risk
Cheung (2019)^Citation22	DM with HP eradication	China	Metformin; non-metformin	7,266 (5,368/1,898)	Reduced GC risk
Zheng (2019)^Citation23	DM	Sweden	Metformin; non-metformin	544,130 (334,506/209,624)	No impact on GC risk
Dulskas (2020)^Citation24	Gastric cancer with T2DM, compared to the expected number	Lithuania	Metformin and other medication; insulin and other medication; metformin and insulin; sulfonylurea	337 (230/18/15/74)	Reduced GC risk

Table 2 Characteristics of Studies on Metformin and Gastric Cancer Survival

Author (Year)	Population	District	Groups	No. of Patients	Results for Metformin Users
Lee (2016)^Citation28	Gastric cancer after gastrectomy	Republic of Korea	Metformin; non-metformin	326 (132/194)	Improved survival, decreased recurrence
Lacroix (2018)^Citation29	Gastric cancer with DM	Belgium	Metformin; non-metformin	298 (228/70)	Improved overall survival
Seo (2019)^Citation30	Gastric cancer after gastrectomy	Republic of Korea	Metformin; non-metformin; non-DM	2,187 (103/139/1,945)	Improved survival, decreased recurrence
Baglia (2019)^Citation31	Gastric cancer with DM	China	Metformin; non-metformin	130	No impact on survival

Figure 1 Potential molecular mechanism of anti-cancer activity of metformin in gastric cancer. The different biological processes and molecules involved were summarized.

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;11:20.21241523

 PubMed Web of Science ®Google Scholar

Ruiter R, Visser LE, van Herk-sukel MP, 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):119–124.22100960

 PubMed Web of Science ®Google Scholar

Kim YI, Kim SY, Cho SJ, 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):854–863.24612291

 PubMed Web of Science ®Google Scholar

Murff HJ, Roumie CL, Greevy RA, et al. Metformin use and incidence cancer risk: evidence for a selective protective effect against liver cancer. Cancer Causes Control. 2018;29(9):823–832.30022336

 PubMed Web of Science ®Google Scholar

Tsilidis KK, Capothanassi D, Allen NE, 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):2522–2532.24898303

 PubMed Web of Science ®Google Scholar

Valent F. Diabetes mellitus and cancer of the digestive organs: an Italian population-based cohort study. J Diabetes Complications. 2015;29(8):1056–1061.26275864

 PubMed Web of Science ®Google Scholar

Tseng CH. Metformin reduces gastric cancer risk in patients with type 2 diabetes mellitus. Aging (Albany NY). 2016;8(8):1636–1649.27587088

 PubMedGoogle Scholar

de Jong RG, Burden AM, de Kort S, et al. No decreased risk of gastrointestinal cancers in users of metformin in the Netherlands; a time-varying analysis of metformin exposure. Cancer Preve Res. 2017;10(5):290–297.

 PubMed Web of Science ®Google Scholar

Cheung KS, Chan EW, Wong AYS, et al. Metformin use and gastric cancer risk in diabetic patients after helicobacter pylori eradication. J Natl Cancer Inst. 2019;111(5):484–489.30329127

 PubMedGoogle Scholar

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):877–882.31591459

 PubMed Web of Science ®Google Scholar

Dulskas A, Patasius A, Kaceniene A, et al. Study of antihyperglycemic medication exposure and gastric cancer risk. J Clin Med. 2020;9(2):435.

 PubMed Web of Science ®Google Scholar

Lee CK, Jung M, Jung I, et al. Cumulative metformin use and its impact on survival in gastric cancer patients after gastrectomy. Ann Surg. 2016;263(1):96–102.25575260

 PubMed Web of Science ®Google Scholar

Lacroix O, Couttenier A, Vaes E, Cardwell CR, De Schutter H, Robert A. Impact of metformin on gastric adenocarcinoma survival: a Belgian population based study. Cancer Epidemiol. 2018;53:149–155.29453032

 PubMed Web of Science ®Google Scholar

Seo HS, Jung YJ, Kim JH, Lee HH, Park CH. The effect of metformin on prognosis in patients with locally advanced gastric cancer associated with type 2 diabetes mellitus. Am J Clin Oncol. 2019;42(12):909–917.31693512

 PubMed Web of Science ®Google Scholar

Baglia ML, Cui Y, Zheng T, et al. Diabetes Medication use in association with survival among patients of breast, colorectal, lung, or gastric cancer. Cancer Res Treat. 2019;51(2):538–546.29986576

 PubMed Web of Science ®Google Scholar