Dataset Information

Association of metformin, aspirin, and cancer incidence with mortality risk in adults with diabetes.

ABSTRACT:

Background

Metformin and aspirin are commonly co-prescribed to people with diabetes. Metformin may prevent cancer, but in older people (over 70 years), aspirin has been found to increase cancer mortality. This study examined whether metformin reduces cancer mortality and incidence in older people with diabetes; it used randomization to 100 mg aspirin or placebo in the ASPirin in Reducing Events in the Elderly (ASPREE) trial to quantify aspirin's impact on metformin users.

Methods

Analysis included community-dwelling ASPREE participants (aged ≥70 years, or ≥65 years for members of US minority populations) with diabetes. Diabetes was defined as a fasting blood glucose level greater than 125 mg/dL, self-report of diabetes, or antidiabetic medication use. Cox proportional hazards regression models were used to analyze the association of metformin and a metformin-aspirin interaction with cancer incidence and mortality, with adjustment for confounders.

Results

Of 2045 participants with diabetes at enrollment, 965 were concurrently using metformin. Metformin was associated with a reduced cancer incidence risk (adjusted hazard ratio [HR] = 0.68, 95% confidence interval [CI] = 0.51 to 0.90), but no conclusive benefit for cancer mortality (adjusted HR = 0.72, 95% CI = 0.43 to 1.19). Metformin users randomized to aspirin had greater risk of cancer mortality compared with placebo (HR = 2.53, 95% CI = 1.18 to 5.43), but no effect was seen for cancer incidence (HR = 1.11, 95% CI = 0.75 to 1.64). The possible effect modification of aspirin on cancer mortality, however, was not statistically significant (interaction P = .11).

Conclusions

In community-dwelling older adults with diabetes, metformin use was associated with reduced cancer incidence. Increased cancer mortality risk in metformin users randomized to aspirin warrants further investigation.

Aspree trial registration

ClinicalTrials.gov ID NCT01038583.

SUBMITTER: Orchard SG

PROVIDER: S-EPMC10042437 | biostudies-literature | 2023 Mar

REPOSITORIES: biostudies-literature

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Publications

Association of metformin, aspirin, and cancer incidence with mortality risk in adults with diabetes.

Orchard Suzanne G SG Lockery Jessica E JE Broder Jonathan C JC Ernst Michael E ME Espinoza Sara S Gibbs Peter P Wolfe Rory R Polekhina Galina G Zoungas Sophia S Loomans-Kropp Holli A HA Woods Robyn L RL

JNCI cancer spectrum 20230301 2

<h4>Background</h4>Metformin and aspirin are commonly co-prescribed to people with diabetes. Metformin may prevent cancer, but in older people (over 70 years), aspirin has been found to increase cancer mortality. This study examined whether metformin reduces cancer mortality and incidence in older people with diabetes; it used randomization to 100 mg aspirin or placebo in the ASPirin in Reducing Events in the Elderly (ASPREE) trial to quantify aspirin's impact on metformin users.<h4>Methods</h4> ...[more]

PMID: 36857596

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Project description:Aims/hypothesisDiabetes is associated with an increased risk of cancer. Prostasin is an epithelial sodium channel stimulator that has been associated with suppression of tumours, glucose metabolism and hyperglycaemia-associated tumour pathology. However, the association between prostasin, diabetes and cancer mortality has not been well investigated in humans. We aim to investigate the associations between plasma prostasin and diabetes, and to explore whether prostasin has an effect on cancer mortality risk in individuals with hyperglycaemia.MethodsPlasma prostasin was measured using samples from the Malmö Diet and Cancer Study Cardiovascular Cohort, and statistical analysis was performed from both sex-specific quartiles and per 1 SD. The cross-sectional association between plasma prostasin and diabetes was first studied in 4658 participants (age 57.5 ± 5.9 years, 39.9% men). After excluding 361 with prevalent diabetes, the associations of prostasin with incident diabetes and cancer mortality risk were assessed using Cox regression analysis. The interactions between prostasin and blood glucose levels as well as other covariates were tested.ResultsThe adjusted OR for prevalent diabetes in the 4th vs 1st quartile of prostasin concentrations was 1.95 (95% CI 1.39, 2.76) (p for trend <0.0001). During mean follow-up periods of 21.9 ± 7.0 and 23.5 ± 6.1 years, respectively, 702 participants developed diabetes and 651 died from cancer. Prostasin was significantly associated with the incidence of diabetes. The adjusted HR for diabetes in the 4th vs 1st quartile of prostasin concentrations was 1.76 (95% CI 1.41, 2.19) (p for trend <0.0001). Prostasin was also associated with cancer mortality There was a significant interaction between prostasin and fasting blood glucose for cancer mortality risk (p for interaction =0.022), with a stronger association observed in individuals with impaired fasting blood glucose levels at baseline (HR per 1 SD change 1.52; 95% CI 1.07, 2.16; p=0.019).Conclusions/interpretationPlasma prostasin levels are positively associated with diabetes risk and with cancer mortality risk, especially in individuals with high blood glucose levels, which may shed new light on the relationship between diabetes and cancer.

Dataset Information

Association of metformin, aspirin, and cancer incidence with mortality risk in adults with diabetes.

Background

Methods

Results

Conclusions

Aspree trial registration

Publications

Association of metformin, aspirin, and cancer incidence with mortality risk in adults with diabetes.

Similar Datasets

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