Metformin use is associated with reduced cancer risk

Two recent studies published in the Journal of the National Cancer Institute have correlated metformin use with lower cancer risks, implying that the drug may offer some protection against the illness.

The first of these studies was a systematic review and meta-analysis published earlier this year. Researchers used databases such as PubMed, MEDLINE, Embase, Cochrane Library, Web of Sciences, and Scopus to gather studies from the start of the databases until March 7, 2023. Investigators categorized metformin use as “ever” or “yes.” Additionally, cancer diagnosis was characterized by outcome.

After sifting through the available studies using the National Heart, Lung, and Blood Institute’s guidelines, the researchers were left with 166 studies.

Across all case-controlled studies analyzed, metformin use correlated with a 45% reduction in overall cancer risk. The reduction was slightly more modest in prospective cohort studies, at 35%.

Beyond its impact on overall cancer risk, the researchers noted that it explicitly reduced the risk of gastrointestinal cancer by 21%. In addition, urologic and hematologic cancer risks declined by 12% and 13%, respectively.

Despite these outcomes, the investigators noted significant publication bias in the studies after assessing them using the Egger test, Begg test, and funnel plots.

They concluded, “Metformin may be associated with a decreased risk of many cancer types, but high heterogeneity and risk of publication bias limit confidence in these results. Additional studies in populations without diabetes are needed to better understand the utility of metformin in cancer prevention.”

Another study published more recently in the Journal of the National Cancer Institute was an observational study assessing the correlation between metformin use and pancreatic cancer.

In that study, researchers noted, "This study unveils immune profile changes resulting from metformin use in upfront resected pancreatic cancer patients, possibly contributing to prolonged survival outcomes. Specifically, metformin use may decrease the abundance and activity of pro-tumoral M2 macrophages and increase the recruitment and function of tumor-resolving DCs, favoring anti-tumor immunity.”

Each of these studies supports the benefits of metformin use in reducing cancer risk; however, researchers need to investigate the connection further and identify the reasons behind these associations.