First-generation weight-loss drugs like liraglutide and exenatide could show anticancer benefits beyond weight loss, according to findings from a retrospective, observational study presented by Sagy et al at the European Congress on Obesity (ECO) 2025 and simultaneously published in eClinicalMedicine.
Background
Both obesity and diabetes are linked to an increased risk for many types of obesity-related cancers, including postmenopausal breast cancer, colorectal cancer, endometrial cancer, meningioma, renal cell carcinoma, hepatobiliary cancers, pancreatic cancer, thyroid cancer, gastric cancer, ovarian cancer, and multiple myeloma.
Glucagon-like peptide (GLP)-1 receptor agonists—which are known for their ability to control type 2 diabetes and obesity—work by mimicking the GLP-1 hormone that lowers blood sugar levels and makes individuals feel fuller for longer.
First-generation GLP-1 receptor agonists and bariatric surgery are well-established weight loss treatments; however, their comparative effectiveness for the prevention of obesity-related cancers is not yet known.
Study Methods and Results
In the study, investigators analyzed the electronic health record data of patients aged 24 years or older with a body mass index (BMI) of 35 kg/m2 or higher, type 2 diabetes, and no prior history of cancer. The patients received first-generation GLP-1 receptor agonists for a minimum of 6 monthly purchases of liraglutide, exenatide, or dulaglutide within 12 months or with bariatric surgery between 2010 and 2018. In total, 6,356 patients were matched 1:1 on the basis of sex, age, BMI at the start of the study, time of treatment initiation, and smoking status. They were followed-up until December 2023.
After a median follow-up of 7.5 years, 298 of the patients were diagnosed with obesity-related cancers. The investigators noted that 26% (n = 77) of patients had postmenopausal breast cancer, 16% (n = 49) had colorectal cancer, and 15% (n = 45) had endometrial cancer.
Further, obesity-related cancers occurred among 4.7% (n = 150/3,178) of the patients who underwent surgery (5.76 cases per 1,000 person-years) and among nearly 4.7% (n = 148/3,178) of those receiving GLP-1 receptor agonists (5.64 cases per 1,000 person-years), despite the relative advantage of bariatric surgery in weight reduction—which is known to reduce the risk of cancer.
To assess the comparative effect beyond the extent of weight loss, the investigators adjusted the analysis for the percent of maximal BMI change during follow-up. They discovered that GLP-1 receptor agonists had a direct effect on reducing obesity-related cancers beyond weight loss, with a 41% lower relative risk compared with bariatric surgery.
Conclusions
“Our study found a similar incidence of obesity-related cancers among patients treated with first-generation [GLP]-1 receptor agonists and with bariatric surgery over an average of 8 years follow-up, despite the relative advantage of surgery in maximizing weight loss,” explained lead study author Yael Wolff Sagy, PhD, of Clalit Health Services in Tel-Aviv, Israel.
“The protective effects of GLP-1 [receptor agonists] against obesity-related cancers likely arise from multiple mechanisms, including reducing inflammation,” suggested co–study author Dror Dicker, MD, Professor of Hasharon Hospital at the Rabin Medical Center in Petah Tikva, Israel. “Our study is unique in that the long-term follow-up allowed us to compare the effects of GLP-1 [receptor agonists] and surgery with potential long latency periods of cancer. New-generation, highly potent GLP-1 [receptor agonists] 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,” he underscored.
The investigators emphasized that their study was observational and that future randomized trials and larger prospective studies may be needed to confirm the effects as well as explore the underlying mechanisms.
“We do not yet fully understand how GLP-1 [receptor agonists] work, but this study adds to the growing evidence showing that weight loss alone cannot completely account for the metabolic, anticancer, and many other benefits that these [drugs] provide,” Dr. Sagy concluded.
Disclosure: For full disclosures of the study authors, visit eco2025.org and thelancet.com.
