Mortality After Incident Cancer in People With and Without Type 2 Diabetes

Abstract

OBJECTIVEType 2 diabetes is associated with an increased risk of several types of cancer and with reduced survival after cancer diagnosis. We examined the hypotheses that survival after a diagnosis of solid-tumor cancer is reduced in those with diabetes when compared with those without diabetes, and that treatment with metformin influences survival after cancer diagnosis.RESEARCH DESIGN AND METHODSData were obtained from >350 U.K. primary care practices in a retrospective cohort study. All individuals with or without diabetes who developed a first tumor after January 1990 were identified and records were followed to December 2009. Diabetes was further stratified by treatment regimen. Cox proportional hazards models were used to compare all-cause mortality from all cancers and from specific cancers.RESULTSOf 112,408 eligible individuals, 8,392 (7.5%) had type 2 diabetes. Cancer mortality was increased in those with diabetes, compared with those without (hazard ratio 1.09 [95% CI 1.06–1.13]). Mortality was increased in those with breast (1.32 [1.17–1.49]) and prostate cancer (1.19 [1.08–1.31]) but decreased in lung cancer (0.84 [0.77–0.92]). When analyzed by diabetes therapy, mortality was increased relative to nondiabetes in those on monotherapy with sulfonylureas (1.13 [1.05–1.21]) or insulin (1.13 [1.01–1.27]) but reduced in those on metformin monotherapy (0.85 [0.78–0.93]).CONCLUSIONSThis study confirmed that type 2 diabetes was associated with poorer prognosis after incident cancer, but that the association varied according to diabetes therapy and cancer site. Metformin was associated with survival benefit both in comparison with other treatments for diabetes and in comparison with a nondiabetic population.

Metformin use and survival from lung cancer: A population-based cohort study

“…Inconsistent with our findings, two previous studies reported significant reductions in all-cause mortality in users of metformin before [13] or after [14] lung cancer diagnosis. A further study reported a shorter overall survival in pre-diagnostic metformin users compared to non-users [12].…”

“…A further study reported a shorter overall survival in pre-diagnostic metformin users compared to non-users [12]. Unlike our investigation, previous studies did not investigate dosedependent relationships [12][13][14] and metformin use after diagnosis was time-fixed [14], thus potentially introducing immortal time bias. Moreover, results from studies investigating allcause mortality could be reflective of non-cancer mortality.…”

“…Some, but not all [8] have reported improvements in progressionfree survival [9] and disease-free survival [10,11] but these investigations were limited by small sample sizes [8][9][10][11], drug exposure determined at limited numbers of time-points [8][9][10][11] and a lack of adjustment for important baseline patient characteristics [9]. Other studies have investigated metformin use and overall survival [12][13][14], but these results could reflect mortality from non-cancer causes.…”

Association between the Metabolic Syndrome and High Tumor Grade and Stage of Primary Urothelial Cell Carcinoma of the Bladder

“…Insulin resistance and hyperinsulinemia are the cornerstone of metabolic syndrome and are also factors for some cancers. The correlation between obesity and increased bladder cancer or bladder recurrence risk need further research to better clarify the potential mechanism (Eckel 2007;Borena et al, 2011;Currie et al, 2012;Lee et al, 2012;Liu et al, 2012).…”

Expression Characteristics of Proteins of the Insulin-like Growth Factor Axis in Non-small Cell Lung Cancer Patients with Preexisting Type 2 Diabetes Mellitus

“…Accumulating epidemiologic evidence suggests that type 2 diabetes mellitus (T2DM) and/or certain diabetes treatments may be associated with prevalence, progression, or prognosis of some malignancies, but the risk may vary according to diabetes therapy and cancer site (Barone et al, 2008;Currie et al, 2012;Wang et al, 2013). For example, the cohorts of patients with T2DM were reported to have increased prevalence in several types of malignancies, such as liver, colorectal, pancreas, endometrial and breast cancers, etc (He et al, 2010;Wang et al, 2012;Elena et al, 2013;Zhang et al, 2013), and the all-cause mortality in patients with preexisting T2DM (preDM) was also increased in those with breast, prostate, pancreas and colorectal cancer, etc (Arif, et al, 2011;Currie et al, 2012;Hwang et al, 2013;Walker et al, 2013). Non-small-cell lung cancer (NSCLC) is the leading cause of cancer-related deaths worldwide (Siegel et al, 2013).…”