Association between metformin and the risk of gastric cancer in patients with type 2 diabetes mellitus: a meta-analysis of cohort studies

Abstract

ObjectivesThe objective of this study was to evaluate the association between metformin therapy and the incidence of gastric cancer (GC) in patients with type 2 diabetes mellitus (T2DM).MethodsWe systemically searched the following databases for studies published between the databases’ dates of inception and Nov. 2016: PubMed, Embase, the Cochrane Library, the Web of Science, and the China National Knowledge Infrastructure (CNKI). Hazard ratios (HR)and corresponding 95% confidence intervals (CIs) for the association between metformin therapy and the incidence of GC in patients with T2DM were the outcome measures assessed in this study. STATA 12.0 (Stata Corporation, College Station, Texas, USA) was used to conduct the statistical analysis.ResultsA total of seven cohort studies including 591,077 patients met all the criteria for inclusion in the analysis. Our data showed that metformin therapy was associated with a significantly lower incidence of GC in patients with T2DM than other types of therapy (HR=0.763, 95% CI: 0.642˜0.905). Subgroup analysis showed that patients living in Taiwan benefitted more from metformin therapy than patients living in any other region, as metformin significantly decreased the risk of GC in patients living in Taiwan but did not significantly decrease the risk of GC in patients living in other regions (HR=0.514, 95% CI: 0.384-0.688). The results of the present analysis support the idea that metformin facilitates reductions in the risk of T2DM-related GC.ConclusionsThe risk of GC among patients with T2DM is lower in patients receiving metformin therapy than in patients not receiving metformin therapy.

Diabetes Increases Risk of Gastric Cancer After Helicobacter pylori Eradication: A Territory-Wide Study With Propensity Score Analysis

“…When compared to individuals with HbA1c levels of 5.0-5.9% [31-41mmol/mol], those with HbA1c levels of  6.0% [42mmol/mol] had more than twofold increase in GC risk. 12 Furthermore, all existing studies failed to adjust for concomitant medication usage which may modulate GC risk including aspirin, 13 nonsteroidal anti-inflammatory drugs (NSAIDs), cyclooxygenase-2 (COX-2) inhibitors, statins, 14 metformin, 15 and proton pump inhibitors (PPIs). 16,17 Failure to adjust for potential chemopreventive agents could bias a positive association between DM and GC to null as a higher proportion of patients with DM may require aspirin, statins and metformin.…”

“…Metformin was associated with a lower GC risk in a meta-analysis. 15 Subgroup analysis was performed according to metformin use, glycemic control (i.e. timeweighted average HbA1c level) and cancer site (cardia and non-cardia).…”

Metformin Use and Gastric Cancer Risk in Diabetic Patients After Helicobacter pylori Eradication

“…While no association between metformin use and GC was reported by some studies, (10,11) others suggested a protective effect with varying effect estimates. (12)(13)(14)(15)(16) A recent meta-analysis (17) concluded that metformin decreased GC risk by 24% but there was a statistically significant heterogeneity among studies. More importantly, other important risk factors of GC including H. pylori infection and DM severity have not been adequately addressed in previous studies, potentially undermining the role of metformin on GC prevention.…”

“…More importantly, other important risk factors of GC including H. pylori infection and DM severity have not been adequately addressed in previous studies, potentially undermining the role of metformin on GC prevention. (17) As H. pylori is the most important risk factor of GC, failure to stratify patients according to H. pylori status will affect the true effect estimate of metformin on GC development. Moreover, GC risk was shown to be higher among individuals with higher hemoglobin A1c (HbA1c) levels (18).…”

The therapeutic potential of metformin in gastric cancer

“…Recently Zhou et al published a meta-analysis of seven cohort studies including a total of 591,077 diabetic patients (type 2). According to this study, the risk of developing a GC in metformintreated diabetic patients is significantly reduced (hazard ratio of 0.76) [21]. It was also demonstrated that survival rate of GC patients is increased in the diabetic patients group treated with metformin compared to the other diabetic patients, not treated with metformin [22].…”