Metformin use among older patients with diabetes is associated with a reduced risk of cancer, but the combination of aspirin and metformin is associated with an increased risk of cancer death, according to research published in JNCI Cancer Spectrum.

Researchers assessed associations between metformin, aspirin, and cancer using data from the ASPREE trial ( Identifier: NCT01038583).

The trial enrolled community-dwelling adults who were 65 years of age or older and did not have cardiovascular disease, dementia, or disability. They were randomly assigned to receive 100 mg of enteric-coated aspirin or placebo daily.

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The study included 17,069 patients who did not have diabetes and 2045 patients who did. In both groups, roughly half of patients were randomly assigned to aspirin, and the other half were assigned to placebo. Among the patients with diabetes, 965 were taking metformin at baseline, and 1080 were not. 

The risk of cancer was lower among diabetic patients who were taking metformin than among those who were not (adjusted hazard ratio [aHR], 0.68; 95% CI, 0.51-0.90). However, there was no significant difference in the risk of cancer death between metformin users and nonusers (aHR, 0.72; 95% CI, 0.43-1.19). 

The risk of cancer was similar for metformin users and participants without diabetes (aHR, 1.09; 95% CI, 0.88-1.35), and the same was true for cancer death (aHR, 1.39; 95% CI, 0.96-2.02). 

However, patients with diabetes who did not use metformin had a higher risk of cancer (aHR, 1.35; 95% CI, 1.13-1.62) and cancer death (aHR, 1.55; 95% CI, 1.12-2.15) than participants who did not have diabetes. 

Among diabetic patients taking metformin, those who were randomly assigned to receive aspirin had a similar risk of cancer as those assigned to placebo (HR, 1.11; 95% CI, 0.75-1.64). However, the risk of cancer death was significantly greater for the metformin users taking aspirin (HR, 2.53; 95% CI, 1.18-5.43).

For diabetic patients not taking metformin, the risk of cancer was similar between those assigned to aspirin and those assigned to placebo (HR, 1.10; 95% CI, 0.79-1.52). The risk of cancer death was similar between these groups as well (HR, 1.16; 95% CI, 0.64-2.09). 

“Aspirin was associated with increased cancer mortality risk in metformin users, but the modification effect of metformin and aspirin did not reach statistical significance [P =.11],” the researchers noted.

They concluded that additional studies are needed to better understand the relationship between aspirin, metformin, and cancer.


Orchard SG, Lockery JE, Broder JC, et al. Association between metformin, aspirin and cancer incidence and mortality risk in adults with diabetes. JNCI Cancer Spectr. Published online March 1, 2023. doi:10.1093/jncics/pkad017

This article originally appeared on Cancer Therapy Advisor