GLP-1 receptor agonists show anti-cancer benefits beyond weight loss

New research being presented at this year’s European Congress on Obesity (ECO) in Malaga, Spain (11-14 May) and published in the journal eClinicalMedicine finds that first generation weight-loss medications like liraglutide and exenatide appear to show anti-cancer benefits beyond weight loss.

“Our study found a similar incidence of obesity-related cancer among patients treated with first-generation glucagon-like peptide-1 receptor agonists (GLP-1s) and with bariatric surgery over an average of 8 years follow-up, despite the relative advantage of surgery in maximising weight loss,” explained co-lead author Dr Yael Wolff Sagy from Clalit Health Services, Tel-Aviv, Israel. “But accounting for this advantage revealed the direct effect of GLP-1RAs beyond weight-loss to be 41% more effective at preventing obesity-related cancer.”

She adds: “We do not yet fully understand how GLP-1s work, but this study adds to the growing evidence showing that weight loss alone cannot completely account for the metabolic, anti-cancer, and many other benefits that these medications provide.”

GLP-1RA medications are best known for helping control type 2 diabetes and treat obesity. They mimic a hormone in the body, GLP-1, that lowers blood sugar levels and makes people feel fuller for longer.

Both obesity and diabetes are linked with an increased risk for many types of cancer, referred as obesity related cancer, including post-menopausal breast cancer, colorectal cancer, corpus uteri cancer, meningioma, renal-cell kidney, liver or bile duct, pancreatic, thyroid, stomach, and ovarian cancer, as well as multiple myeloma.

First generation GLP-1s and bariatric surgery are well established weight loss treatments, but their comparative effectiveness for the prevention of obesity-related cancers is not known.

To find out more, researchers analysed electronic health record data for patients (aged 24 years or older) with obesity (BMI of 35 kg/m² or higher) and type 2 diabetes (with no prior history of cancer), who were treated with first-generation GLP-1s (i.e., for a minimum of six monthly purchases of liraglutide, exenatide, or dulaglutide within 12 consecutive months) or with bariatric surgery between 2010 and 2018 from Clalit health services—which insures over half of the Israeli population (approximately 4.8 million patients).

In total, 6,356 participants (61% females; average age 52 years; mean BMI 41.5 kg/m²) were matched 1:1 based on sex, age, BMI at the start of the study, time of treatment initiation, and smoking status. They were followed-up until December 2023 for a diagnosis of obesity-related cancer.

Over a median follow-up of 7.5 years, 298 patients were diagnosed with obesity-related cancer. The most common cancer was postmenopausal breast cancer (77; 26%), followed by colorectal cancer (49; 16%), and cancer of the uterus (45; 15%).

The analysis found that obesity-related cancer occurred in 150 of 3,178 surgery patients (5.76 cases per 1,000 person-years) and in 148 of 3,178 patients taking GLP-1s (5.64 cases per 1,000 person-years), despite the relative advantage of bariatric surgery in weight reduction, that is known to reduce cancer risk.

To assess the comparative effect beyond the extent of weight-loss (which mediates the reduction in cancer risk following treatment), the researchers further adjusted the analysis for the percent of maximal BMI change during follow-up (i.e., how much an individual's BMI changed).

They found that GLP1-RAs had a direct effect on reducing obesity-related cancer beyond weight-loss, with a 41% lower relative risk compared to bariatric surgery.
“The protective effects of GLP1-RAs against obesity-related cancers likely arise from multiple mechanisms, including reducing inflammation,” said co-lead author Professor Dror Dicker from Hasharon Hospital, Rabin Medical Center, Petah Tikva, Israel. “Our study is unique in that the long-term follow-up allowed us to compare the effects of GLP1-RAs and surgery with potential long latency periods of cancer. New generation, highly potent GLP1-RAs with higher efficacy in weight reduction may convey an even greater advantage in reducing the risk of obesity-related cancers, but future research is needed to make sure that these drugs do not increase the risk for non–obesity-related cancers.”Despite the important findings, the authors note that this is an observational study and that future randomised trials and larger prospective studies are needed to confirm the effects and explore the underlying mechanisms.