Dataset Information

Mortality after incident cancer in people with and without type 2 diabetes: impact of metformin on survival.

ABSTRACT:

Objective

Type 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 methods

Data 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.

Results

Of 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]).

Conclusions

This 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.

SUBMITTER: Currie CJ

PROVIDER: S-EPMC3263862 | biostudies-literature | 2012 Feb

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Mortality after incident cancer in people with and without type 2 diabetes: impact of metformin on survival.

Currie Craig J CJ Poole Chris D CD Jenkins-Jones Sara S Gale Edwin A M EA Johnson Jeffrey A JA Morgan Christopher Ll CL

Diabetes care 20120120 2

<h4>Objective</h4>Type 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.<h4>Research design and methods</h4>Data were obtained from >350 U.K. primary care practices in a retrospective cohor ...[more]

PMID: 22266734

Similar Datasets

Project description:Aims/hypothesisMetformin is the most-prescribed oral medication to lower blood glucose worldwide. Yet previous systematic reviews have raised doubts about its effectiveness in reducing risk of cardiovascular disease, the most costly complication of type 2 diabetes. We aimed to systematically identify and pool randomised trials reporting cardiovascular outcomes in which the effect of metformin was 'isolated' through comparison to diet, lifestyle or placebo.MethodsWe performed an electronic literature search of MEDLINE, EMBASE and the Cochrane Library. We also manually screened the reference lists of previous meta-analyses of trials of metformin identified through a MEDLINE search. We included randomised controlled trials of adults with type 2 diabetes comparing any dose and preparation of oral metformin with no intervention, placebo or a lifestyle intervention and reporting mortality or a cardiovascular outcome.ResultsWe included ten articles reporting 13 trials (including a total of 2079 individuals with type 2 diabetes allocated to metformin and a similar number to comparison groups) of which only four compared metformin with placebo and collected data on cardiovascular outcomes. Participants were mainly white, aged ≤65 years, overweight/obese and with poor glycaemic control. Summary estimates were based on a small number of events: 416 myocardial infarctions/ischaemic heart disease events in seven studies and 111 strokes in four studies. The UK Prospective Diabetes Study (UKPDS) contributed the majority of data to the summary estimates, with weights ranging from 52.3% for myocardial infarction to 70.5% for stroke. All outcomes, with the exception of stroke, favoured metformin, with limited heterogeneity between studies, but none achieved statistical significance. Effect sizes (Mantel-Haenszel RR) were: all-cause mortality 0.96 (95% CI 0.84, 1.09); cardiovascular death 0.97 (95% CI 0.80, 1.16); myocardial infarction 0.89 (95% CI 0.75, 1.06); stroke 1.04 (95% CI 0.73, 1.48); and peripheral vascular disease 0.81 (95% CI 0.50, 1.31).Conclusions/interpretationThere remains uncertainty about whether metformin reduces risk of cardiovascular disease among patients with type 2 diabetes, for whom it is the recommended first-line drug. Although this is mainly due to absence of evidence, it is unlikely that a definitive placebo-controlled cardiovascular endpoint trial among people with diabetes will be forthcoming. Alternative approaches to reduce the uncertainty include the use of electronic health records in long-term pragmatic evaluations, inclusion of metformin in factorial trials, publication of cardiovascular outcome data from adverse event reporting in trials of metformin and a cardiovascular endpoint trial of metformin among people without diabetes.

Project description:BackgroundThe relation between body weight and mortality among persons with type 2 diabetes remains unresolved, with some studies suggesting decreased mortality among overweight or obese persons as compared with normal-weight persons (an "obesity paradox").MethodsWe studied participants with incident diabetes from the Nurses' Health Study (8970 participants) and Health Professionals Follow-up Study (2457 participants) who were free of cardiovascular disease and cancer at the time of a diagnosis of diabetes. Body weight shortly before diagnosis and height were used to calculate the body-mass index (BMI, the weight in kilograms divided by the square of the height in meters). Multivariable Cox models were used to estimate the hazard ratios and 95% confidence intervals for mortality across BMI categories.ResultsThere were 3083 deaths during a mean period of 15.8 years of follow-up. A J-shaped association was observed across BMI categories (18.5 to 22.4, 22.5 to 24.9 [reference], 25.0 to 27.4, 27.5 to 29.9, 30.0 to 34.9, and ≥35.0) for all-cause mortality (hazard ratio, 1.29 [95% confidence interval {CI}, 1.05 to 1.59]; 1.00; 1.12 [95% CI, 0.98 to 1.29]; 1.09 [95% CI, 0.94 to 1.26]; 1.24 [95% CI, 1.08 to 1.42]; and 1.33 [95% CI, 1.14 to 1.55], respectively). This relationship was linear among participants who had never smoked (hazard ratios across BMI categories: 1.12, 1.00, 1.16, 1.21, 1.36, and 1.56, respectively) but was nonlinear among participants who had ever smoked (hazard ratios across BMI categories: 1.32, 1.00, 1.09, 1.04, 1.14, and 1.21) (P=0.04 for interaction). A direct linear trend was observed among participants younger than 65 years of age at the time of a diabetes diagnosis but not among those 65 years of age or older at the time of diagnosis (P<0.001 for interaction).ConclusionsWe observed a J-shaped association between BMI and mortality among all participants and among those who had ever smoked and a direct linear relationship among those who had never smoked. We found no evidence of lower mortality among patients with diabetes who were overweight or obese at diagnosis, as compared with their normal-weight counterparts, or of an obesity paradox. (Funded by the National Institutes of Health and the American Diabetes Association.).

Dataset Information

Mortality after incident cancer in people with and without type 2 diabetes: impact of metformin on survival.

Objective

Research design and methods

Results

Conclusions

Publications

Mortality after incident cancer in people with and without type 2 diabetes: impact of metformin on survival.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets