Metformin may reduce risk for overall cancer, GI malignancies, meta-analysis shows
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The commonly used diabetes drug metformin may reduce risk for cancer, according to study results published in Journal of the National Cancer Institute.
A systematic review and meta-analysis of 166 studies revealed a decreased risk for overall cancer in case-control studies (RR = 0.55; 95% CI, 0.3-0.8) and in prospective cohort studies (RR = 0.65; 95% CI, 0.37-0.93).
An analysis that grouped cancers by organ system revealed a “striking association” between metformin and reduced risk for gastrointestinal cancers, according to researcher Holli Loomans-Kropp, PhD, MPH, assistant professor in the division of cancer prevention and control at The Ohio State University James Comprehensive Cancer Center.
“We’ve been using metformin for a long time, and we know the safety and toxicity profiles of this drug, so that does make it prime for investigation and an intriguing drug to use for this purpose,” Loomans-Kropp told Healio. “The next big question is how this drug could be used in a nondiabetic population. I am interested in what long-term use of metformin would look like in terms of cancer preventive efficacy.”
Healio spoke with Loomans-Kropp about the current evidence for metformin’s potential protective properties against cancer, the new insights that emerged from this study, and next steps in research in this area.
Healio: What did existing evidence suggestion about metformin’s protective properties against cancer, and what additional questions did you aim to answer?
Loomans-Kropp: There have been mechanistic studies looking at the antitumor activity of metformin. Much of that has been focused on how the drug could reduce cellular proliferation. There have also been a few randomized trials that analyzed the effects of metformin on cancer risk, but those trials also focused on those measures of proliferation and apoptosis, and many of those trials were relatively short term. To this point, there has not been a comprehensive review of the literature assessing the relationship between metformin and cancer risk. That was the objective of our study — to take that more comprehensive approach.
Healio: How did you conduct the study?
Loomans-Kropp: We performed an in-depth search of the literature, which identified studies that referred to metformin or any of its analogs, as well as cancer incidence information. We kept it broad. This yielded an initial pool of more than 6,000 articles, which we further screened for eligibility. We ended up with 166 studies included in the analysis, then we stratified our analysis by cancer type as well as study type.
Healio: What did you find?
Loomans-Kropp: We saw a general decreased risk for overall cancer in several of the study types, as well as decreased risk for colorectal cancer and liver cancer. There weren’t any consistent associations for breast or prostate cancers.
We also conducted an analysis that grouped cancers by organ system, and we looked at gynecologic, hematologic and digestive cancers. The most striking association was observed for gastrointestinal cancer risk, which showed a summary risk reduction of 21%. It is important to note that there was substantial heterogeneity between studies. We decided not to provide a summary analysis for specific cancer types because of this heterogeneity, which was likely due to different study designs. Over the years, there have been many case-control studies, some perspective cohort studies and some retrospective cohort studies. We didn’t feel it was an accurate reflection of the data to put together a summary analysis.
Healio: What do you consider the key takeaways from this study?
Loomans-Kropp: Our key takeaway message — based on the compilation of decades of research —- is that metformin may have cancer preventive potential. It is important to note that the majority of these studies took place in populations with type 2 diabetes. Metformin is one of the most commonly used antidiabetic medications, whether it’s used in monotherapy or in combination therapy. Few of these studies included individuals without diabetes, and that could be very interesting to look at in the future. We’d like to know how this drug could be used in a nondiabetic population. Would we see similar benefits? Because metformin is commonly used and because we have knowledge of its safety profile, answering this question seems very possible.
Healio: What additional questions remain?
Loomans-Kropp: One question I believe needs to be answered is not just whether metformin reduces cancer risk, but how does it exert this effect? It is great to have these studies that show a risk reduction, but understanding how this is happening is an important question to ask.
Healio: What are your next steps in research?
Loomans-Kropp: We are actively pursuing research into this at my lab. We’re working toward better understanding the effects of metformin at a cellular level using in vitro models of colorectal cancer. We’re also investigating how this can be applied to other cancer types. We’re also interested in evaluating the interaction between different types of commonly used medications. For example, we are examining the potential synergism between nonsteroidal anti-inflammatory drugs, which also are frequently used, and whether this could confer a potential risk reduction. There is a good deal of work we can do in this area.
Healio: Is there anything else you would like to mention?
Loomans-Kropp: The goal of this study was to look at everything we have learned over the years, and compile everything together to see what trends emerged from the literature. We didn’t set any beginning points or endpoints on our search — we looked at everything. Nothing this comprehensive has been done before. We hope it can be used to launch additional studies. I hope I get to be a part of that, but I hope other researchers will take this up, as well. We could use this as a launching point to investigate further.
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For more information:
Holli Loomans-Kropp, PhD, MPH, can be reached at The Ohio State University Comprehensive Cancer Center, Gateway C, 1590 N. High St., Columbus, OH 43201; email: holli.loomans-kropp@osumc.edu.
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