Anti-obesity drugs halve mortality from colon cancer

Researchers hypothesise that Glp-1s reduce systemic inflammation, improve insulin sensitivity and modify the tumour microenvironment, making it less favourable for the growth and spread of cancer cells. In experimental models, these molecules appear to directly block the proliferation of cancer cells and induce their programmed death (apoptosis), as well as remodelling the surrounding tissue by reducing the supply of nutrients to the malignant cells.

'This is a potentially disruptive effect,' Cuomo comments, 'but we still need to understand whether the observed relationship is causal. We need prospective clinical trials to verify whether Glp-1 can really improve survival in obesity-related cancers'.

The researchers used the University of California Health Data Warehouse, one of the largest clinical databases in the world, to compare the outcomes of cancer patients treated with and without Glp-1. After excluding the influence of confounding factors (age, Bmi, tumour stage and comorbidities), the difference in mortality remained significant, indicating a possible effect independent of simple metabolic improvement.

The authors urge caution: this is an observational analysis, not a clinical trial, and therefore does not prove a cause-and-effect relationship. However, the data outline a promising line of research, especially in obesity-associated cancers. 'We are witnessing a convergence between metabolism, inflammation and oncology,' Cuomo concludes. 'If the results are confirmed, we could be looking at one of the most significant discoveries in recent years in translational medicine.

Ucsd's discovery is part of a changing scientific and industrial context: in recent years, Glp-1 drugs have become a global case by proving to be multifunctional, with benefits on different organs and systems. Studies have shown that in patients with type 2 diabetes and chronic kidney disease semaglutide reduces the risk of major kidney events by 24%, and that there is a causal relationship between semaglutide use and reduced alcohol consumption in patients with alcohol use disorder. Incretin drugs would also have important cardiovascular benefits.

After the first generation of Glp-1 agonists, a new wave of multi-incretin therapies, capable of acting on multiple metabolic axes and even on cellular programmes regulating energy balance, is now emerging.

Eli Lilly, for example, has just published in The New England Journal of Medicine the phase III results of its orforglipron, an oral Glp-1 agonist (considered its next blockbuster). The company also announced a EUR 2.6 billion investment to build a new plant dedicated to the production of this drug, expecting 500 jobs (the company already has four plants, in France, Ireland, Italy and Spain, and plans to add two more in Europe). Also in the field are start-up Metsera with its weekly oral Glp-1; and Viking Therapeutics, Hanmi Pharmaceutical and Altimmune, which are developing multi-receptor agonists (Gip/Glp-1/glucagon), promising superior efficacy and synergistic actions on metabolism.

A competitive and rapidly expanding scenario, in which the discovery that these drugs could also affect cancer survival reinforces the idea that the pharmacology of obesity is becoming capable of affecting multiple dimensions of human health, from metabolism to the heart to cancer.

Meanwhile, European regulatory authorities are taking action on the public information front. The Ema has launched the social campaign #HealthNotHype, created with content creators from seven countries, to promote safe and informed use of Glp-1 drugs and counter misinformation related to their use.

As Emer Cooke, Executive Director of the European Medicines Agency (EMA), reminded us, 'these drugs are not magic solutions for losing weight, but long-term therapies to be used under medical supervision'.