Diabetes, metformin use, and survival in esophageal cancer: a population-based cohort study

Abstract

Background It is unclear how diabetes and metformin use is associated with survival of esophageal cancer. Methods This population-based cohort study included new cases of esophageal cancer reported in Sweden from 2006-2018 with follow-up through 2019. Diabetes status and metformin use were analyzed in relation all-cause and disease-specific mortality using multivariable Cox regression. The hazard ratios (HR) with 95% confidence intervals (CI) were adjusted for age, sex, calendar year, obesity, comorbidity, and use of non-steroidal anti-inflammatory drugs or statins. For comparison reasons, three other antidiabetic medications were also analyzed, i.e., sulfonylureas, insulin, and thiazolidinedione. Results Among 4851 esophageal cancer patients (8404 person-years), 4072 (84%) died during follow-up. Compared with esophageal cancer patients with diabetes but not using metformin, decreased all-cause mortality was indicated among non-diabetic patients (without metformin) (HR 0.86, 95% CI 0.77-0.96) and diabetic patients who used metformin (HR 0.86, 0.75-1.00). The HRs of all-cause mortality decreased with a higher daily dose of metformin (Ptrend=0.04). The corresponding HRs for disease-specific mortality were similar but slightly attenuated. The results were also similar in separate analyses of esophageal cancer patients with adenocarcinoma or squamous cell carcinoma, with tumor stage I-II or III-IV, and in those who had or had not undergone surgery. No associations with mortality outcomes were found for use of sulfonylureas, insulin, or thiazolidinedione. Conclusions Diabetes was associated with an increased all-cause mortality while metformin use was associated with decreased all-cause mortality among esophageal cancer patients. More research is needed to determine if metformin affects survival in esophageal cancer.

Glycemic Traits and Oesophageal Cancer a Two-Sample and Multivariable Mendelian Randomization Study

“…Metformin may potentially enhance the release of 5'adenosine monophosphate (AMP-) activated protein kinase (AMPK) at a low level of insulin in the blood, thus impeding the production and elevation of cancerous cellular proteins [32]. Nevertheless, recent investigations on the in uence of metformin in decreasing the occurrence of oesophageal cancer have contradictory ndings [33,34]. More large-scale research is necessary to elucidate its signi cance in reducing the risk of oesophageal cancer among individuals with T2DM.…”

Metformin in Esophageal Carcinoma: Exploring Molecular Mechanisms and Therapeutic Insights

“…Wang et al investigated the relationship between diabetes, metformin use, and survival in EC patients focusing on all-cause and disease-specific mortality [ 40 ]. They suggested that EC patients with diabetes but not using metformin had increased all-cause mortality.…”

“…They also found a trend of decreasing all-cause mortality with a higher daily dose of metformin. They did not find associations between mortality outcomes and other antidiabetic medications like sulfonylureas, insulin, or thiazolidinedione [ 40 ]. However, more research is needed to determine the specific impact of metformin on survival in EC.…”

“…The above are summarized in Table 1. [40]. They suggested that EC patients with diabetes but not using metformin had increased all-cause mortality.…”