The use of glucagon-like peptide-1 receptor agonists (GLP-1 RAs) among patients with diabetes and cancer results in significantly reduced mortality and hospitalizations relative to treatment with metformin, a study has shown.
Furthermore, patients already on metformin and newly started on GLP-1 RAs experience prolonged survival than those newly started on insulin, suggesting the viability of GLP-1 RAs as second-line agent in active cancer.
“[T]he observed reduced rates of hospitalization, severe infection, and atherosclerotic and thrombotic events [also] suggest further unexplored benefits of GLP-1 RAs,” according to the researchers, who identified 3,747 patients with type 2 diabetes who received GLP-1 RAs within 3 months of initiating systemic therapy and 52,061 on metformin as controls using the global database TriNetX.
Subanalyses were also performed to stratify patients by HbA1c range, obesity, and by participants “newly started” on their first instance of GLP-1 RA within 3 months of starting cancer therapy.
Patients who received GLP-1 RAs showed improved survival outcomes both in the overall monotherapy setting (hazard ratio [HR], 0.875, 95 percent confidence interval [CI], 0.778‒0.985; p=0.0268) and the new-start setting (HR, 0.786, 95 percent CI, 0.662‒0.934; p=0.0062) cohorts. [J Clin Endocrinol Metab 2026;111:1604-1612]
In secondary analyses, patients on GLP-1 RAs also benefitted from reduced rates of all-cause hospitalization, sepsis, major adverse cardiovascular events, pulmonary embolism, and pneumonia. However, subanalyses stratified by BMI and HbA1c did not reach statistical significance.
“Future prospective studies should evaluate the benefits of GLP-1RAs in patients with cancer in comparison to other antihyperglycaemic medications to further elucidate these potential benefits,” the researchers said.
Active cancer
The use of insulin has been associated with worse survival among patients with active cancer, and these survival trends are also observed in studies comparing insulin with noninsulin antihyperglycaemic agents. [Diabetologia 2014;57:927-940; J Clin Endocrinol Metab 2019;104:1520-1574; Diabetes Obes Metab 2025;doi:10.1111/dom.70311]
“These findings are supported by preclinical studies demonstrating that insulin upregulates cellular proliferation pathways implicated in cancer, activates the insulin receptor and insulin-like growth factor receptor implicated in tumourigenesis, and may even enhance tumour angiogenesis,” the researchers said. [Int J Mol Sci 2023;24:15006; Diabetologia 2010;53:966-970; Biochem Biophys Res Commun 2023;642:85-93]
“The superior survival outcomes in patients receiving GLP-1 RAs compared to insulin suggest that GLP-1 RAs are viable antihyperglycaemics in patients with cancer, particularly when paired with metformin,” they added.
Obesity
Cachexia in patients with active cancer also results in weight loss and anorexia through the release of inflammatory cytokines. [Nat Rev Dis Primer 2018;4:17105; Exp Mol Med 2022;54:426-432]
“The role of obesity and cancer is complex and multidirectional, and studies conflict regarding the role of overweight and obesity as a protective factor in patients with active cancer,” said the researchers. [JAMA Netw Open 2024;7:e2425363; Cancer 2025;131:e35799]
“While we controlled for obesity as part of our propensity matching in the primary cohort, cohort-based differences in the obesity and nonobese cohorts suggest that patients with cancer and obesity may be more likely to benefit from GLP-1 RA therapy,” they added.
It is also unlikely for someone who was cancer-related cachexia or anorexia to continue or initiate treatment with GLP-1 RA, emphasizing the need for prospective data, according to the researchers.
“Taken together, these findings indicate the need for prospective studies to further explore the interplay of GLP-1 RA and obesity in patient outcomes,” they said.