Anti-obesity drugs could reduce the metastatic risk of certain cancers

For four of the seven tumour types studied (lung, breast, colorectum and liver), persons on GLP-1 therapy were 38 to 50 per cent less likely to progress to stage IV than persons on glyptine therapy. And in these four tumours, metastases appeared at a lower rate in the GLP-1-treated group than in the gliptin group. Specifically, 10% of the GLP-1 group developed metastases in the lung cancer compared to 22% in the gliptin group; for the breast the respective percentages were 10% versus 20%; for the colon-rectum: 13% versus 22%, for the liver 19% versus 28%. In the other three tumours (prostate, pancreas, kidney) the GLP-1-treated group showed less progression to metastasis than the other group, but the difference was not statistically significant.

Overall, therefore, high expression of the GLP-1 receptor (GLP-1R) was associated with a 33% lower risk of death, compared to low expression. This was particularly true in breast cancer, where the risk was reduced by 45%.

The association between elevated expression of the target receptor in treatment with GLP-1-based drugs and improved survival therefore suggests that these drugs may have a protective effect in these cancers. But this is an observational study, which cannot therefore prove a cause-and-effect relationship.

"Our study," comments the study's lead author Mark David Orland of the Cleveland Clinic, "showed that the use of GLP-1 drugs, compared to glyptins and other antidiabetic drugs, is associated with a significant reduction in cancer progression in four types of solid tumours. And this provides preliminary scientific evidence justifying further studies'.

Current research is trying to understand how GLP-1-based drugs can control cancer progression. Among the hypotheses on the table are whether they act directly on tumour cells to prevent their growth; influence the immune system and its ability to attack tumour cells; play a role in inflammation; or alter the way cancer cells obtain the energy they need to survive and multiply.

Randomised controlled clinical trials of GLP-1 drugs in people with cancer are already planned, which could provide stronger evidence on the relationship between GLP-1 and cancer progression.

"GLP-1 receptor agonists," recalls Marcin Chwistek, director of the Supportive Oncology and Palliative Care programme at Fox Chase Cancer Center and ASCO expert in supportive care, "have never been just blood glucose-lowering drugs. Their anti-inflammatory and immunomodulatory properties have long suggested that they may have more far-reaching effects. The results from a study of these numbers, and the consistency of the outcome in different tumour types, justify prospective randomised trials."

One must always be very cautious when talking about cancer. So as not to delude patients in the first place and not to give too much hype to news that may later turn out to be bubbles, as has already happened in the recent past with vitamin D and omega-3. But there is a much more solid rationale for the role of GLP-1-based drugs in the treatment of certain cancers. Thus, at least the hope that these drugs can help curb the aggressiveness of certain tumours is not only legitimate, but also scientifically plausible. Randomised case-control studies will now be needed to verify and validate this, which for the moment is still only an important promise.