TOPLINE:

GLP-1 receptor agonists (RAs) were associated with a 17% lower overall cancer risk in adults with obesity or overweight, with particularly reduced risks for endometrial, ovarian, and meningioma cancers. However, kidney cancer risk may be heightened.

METHODOLOGY:

• Several studies have linked GLP-1 RA use to lower risks for obesity-related cancers, but all have focused on patients with type 2 diabetes. Whether the same associations exist among patients with overweight or obesity, with or without diabetes, remains unclear.
• To investigate, researchers conducted a target trial emulation using a database with electronic health records from 20 million patients at 14 healthcare organizations. They included 86,632 adults eligible for antiobesity medications, defined as those with obesity (BMI, ≥ 30) or overweight (BMI, 27-29.9) with at least one weight-related comorbidity.
• Of these, 43,317 initiated a GLP-1 RA (liraglutide, semaglutide, or tirzepatide), and 43,315 matched individuals did not. The mean age was 52.4 years; 68.2% were women; 44.2% were non-Hispanic White individuals, and 28.8% were non-Hispanic Black individuals; 50.7% had type 2 diabetes; 48.3% had obesity; and the mean BMI was 38.4.
• The study outcomes were the incidence of 14 cancer types: 13 obesity-associated cancers (meningioma, multiple myeloma, and liver, thyroid, pancreatic, bladder, colorectal, kidney, breast, endometrial, upper gastrointestinal, ovarian, and prostate cancers) and lung cancer.

TAKEAWAY:

• The cumulative cancer incidence during follow-up was lower among GLP-1 RA users than among nonusers (891 vs 1022 events). Incidence rates were 13.6 vs 16.4 per 1000 person-years for GLP-1 RA users vs nonusers (hazard ratio [HR], 0.83; P = .002).
• GLP-1 RAs were associated with a significantly lower risk for endometrial cancer (HR, 0.75; P = .05), ovarian cancer (HR, 0.53; P = .04), and meningioma (HR, 0.69; P = .05). Trends toward lower risks were also observed for pancreatic, bladder, and breast cancers.
• However, there was also a trend toward increased kidney cancer risk among GLP-1 RA users (HR, 1.38; 95% CI, 0.99-1.93), especially individuals younger than 65 years and those with overweight.
• The patterns seen in this study and others raise the hypothesis that GLP-1 RA use may be particularly associated with lower risks for hormone-sensitive cancers, but more research on mechanisms is needed, the authors of the study wrote.

IN PRACTICE:

“These findings highlight the importance of tailored risk assessments and underscore the need for further long-term studies to clarify the impact of GLP-1 RAs on cancer risk in high-risk populations,” the authors of the study concluded.

The patterns seen in this study and others raise the hypothesis that GLP-1 RA use may be particularly associated with lower risks for hormone-sensitive cancers, but more research on mechanisms is needed, the authors of the study wrote.

An expert not involved in the study expressed caution about overinterpreting the findings, given the limitations of observational data. In particular, the cancer risk difference is apparent within the first year of GLP-1 initiation, then levels off thereafter, Paul Pharoah, PhD, professor of cancer epidemiology, Cedars-Sinai Medical Center in Los Angeles, explained in a statement from the UK nonprofit Science Media Centre. “This pattern is unlikely if GLP-1 receptor agonists had a causal relationship with cancer risk,” Pharoah said. But “such a pattern could easily be explained by increased health surveillance occurring in the months/years before individuals are prescribed these drugs.”

SOURCE:

The study, led by Hao Dai, PhD, Indiana University School of Medicine, Indianapolis, was published online in JAMA Oncology.

LIMITATIONS:

The study was observational and subject to potential unmeasured confounding, including lack of longitudinal BMI and glycemic control data. Limiting the cohort to patients who are cancer-naive could have reduced generalizability to individuals with prior or secondary malignancies. Additionally, the machine learning-based analyses were limited by data quality.

DISCLOSURES:

This study was supported by the National Institutes of Health’s National Institute of Diabetes and Digestive and Kidney Diseases. One author reported serving on data and safety monitoring boards of Seagen, Nihon Medi-Physics, KAHR Medical, and Arbele; consulting for Avammune Therapeutics, BillionToOne, Exact Sciences, and Summit Therapeutics; and receiving research support to his institution from multiple pharmaceutical companies. Additional disclosures are noted in the original article.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.