The GLP-1 Paradox in Colorectal Cancer

This transcript has been edited for clarity.

Hi. I'm David Kerr, professor of cancer medicine at University of Oxford. One of the harder lessons I've learned as a cancer doctor, not surprisingly, is that prevention's better than cure. This is something I've become increasingly interested in as I've become more senior in the profession. I say that rather than "becoming older."

I'd like to draw your attention to some interesting work that's been done looking at the risk of developing colorectal cancer. We talk about lifestyle factors, exercise, vitamin D, and sometimes aspirin. There is some plausible evidence, not from randomized trials, suggesting that these interventions can reduce the chance of developing colorectal cancer. With my friend Ian Tomlinson, colleague in Oxford, we have a huge interest in the genetics of predicting who will develop colorectal cancer.

Today I'd like to talk about these new agents, the so-called glucagon-like peptide 1 receptor agonists, or GLP-1 receptor agonists, which are being used widely now to treat type 2 diabetes and obesity. These are remarkably successful drugs with huge worldwide global uptake, but there is debate in the literature and in real-world evidence as to what they do about cancer risk.

You would think that if we reduce body weight and if we reduce adiposity, that truly would reduce the chance of developing cancer. We know that a number of cancers are related to body fat content and so on.

I'd like to focus particularly on my own field of interest, which is colorectal cancer, and an article I picked up recently by Professor Zhong and colleagues, where they did a meta-analysis. This is a statistical method for clumping together large datasets from different studies.

They did a meta-analysis using very conventional, widely accepted methods to look at a very large dataset of just over 5 million individuals from seven retrospective cohort studies, so a big database to study.

There was a pooled analysis, which revealed that there was a significant but slight increase in the risk for colorectal cancer in patients receiving the GLP-1 agonists. Overall, they felt that, given the small but significant increase in the risk of developing colorectal cancer, we need further evidence.

This was a retrospective review of a large dataset, but given debate in the literature, more forward-looking studies are required. It’s the sort of thing that, in real-world use, one might take into account when recommending these treatments, such as Mounjaro.

In patients who have a higher-than-expected risk of developing colorectal cancer, one might hesitate a little. Clearly, if they get diabetes or cardiac disease, those beneficial risks would, of course, weigh one in favor of using these effective new drugs.

For somebody who had borderline BMI, where there were some questions as to whether you would use the drugs or not, and if they had some other colorectal cancer risk factors, such as relatives affected, then one might pause for thought before using them.

This was a well-conducted study that adds to the rather confused literature on the effects of these widely used drugs on the risk for cancer. Again, just that thought that, although it would seem plausible to think the opposite, these drugs would reduce colorectal cancer risk, on review of a very large dataset, actually the opposite seems to be the case. Always go for evidence. The larger, the more convincing the dataset, the better.

I’d be interested in what you thought about this and whether information like this might tip your balance as to whether you would accept using these drugs to reduce your own body weight.

Thanks for listening. For the time being, Medscapers, over and out. Thank you.

A version of this article first appeared on Medscape.com.