First-generation GLP-1 receptor agonists provide comparable protection against obesity-related cancers as bariatric surgery in patients with obesity and diabetes, according to the results of an observational, retrospective cohort study.
Researchers conducted a matched cohort study of 3,178 pairs of patients with obesity and diabetes who received either first-generation GLP-1 RAs or underwent bariatric metabolic surgery (BMS) between 2010 and 2018. Participants were followed for a median of 7.5 years and up to 12.9 years.
The analysis documented obesity-related cancer (ORC) in 5.62 cases per 1,000 person-years in BMS patients and 5.89 cases per 1,000 person-years in GLP-1 RA patients. Notably, when researchers assessed potential mediation through weight loss, they found a direct effect of 41% on relative risk reduction associated with pharmacotherapy.
"This may point at additional pathways beyond weight loss in which GLP-1 RAs might contribute to the decreased risk for ORC, such as reducing inflammation," noted Yael Wolff Sagy, PhD, Clalit Health Services, Tel-Aviv, Israel, and colleagues.
Patients were matched 1:1 based on sex, age, baseline BMI, treatment initiation time, and smoking status. Of the 6,356 study participants, 61.1% were female, with a mean age of 52.3 years and mean BMI of 41.5 kg/m². Among BMS patients, 49% underwent sleeve gastrectomy, 40% had gastric bypass, and 11% received laparoscopic banding. In the GLP-1 RA group, 73% received liraglutide, 13% exenatide, and 11% dulaglutide, with the remaining 4% receiving lixisenatide or combinations with insulin.
The study defined ORC as any diagnosis of multiple myeloma, meningioma, adenocarcinoma of the esophagus, stomach, colorectal, liver or bile duct, gallbladder, pancreas, corpus uteri, ovary, renal-cell kidney, thyroid, or postmenopausal breast cancer.
BMS patients achieved an average maximal BMI reduction of 31.1%, compared to 12.9% among GLP-1 RA patients.
"Results from in-vitro and pre-clinical studies suggest anti-inflammatory properties of GLP-1RAs that may modulate the immune system. GLP-1 RAs have been associated with reductions in inflammation processes, including cardiovascular inflammation processes (notably monocyte adhesion and macrophage accumulation), neuroinflammation, and in chronic inflammatory skin disorders," noted investigators.
The study had limitations, including its observational nature, relatively modest sample size, and focus on first-generation GLP-1 RAs rather than newer agents. The authors acknowledged that "a similar comparative effectiveness analysis of BMS versus new generation, highly potent GLP1-RAs may produce different results than those of the current study."
The researchers called for randomized controlled trials and larger prospective cohort studies to validate their findings and explore underlying mechanisms.
Disclosures can be found in the published study.
Source: eClinicalMedicine
