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.
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