GLP-1 drugs linked to lower obesity-related cancer risk

Clinical takeaway: When choosing glucose-lowering therapy for patients with type 2 diabetes, continue to prioritize established cardiovascular, kidney, metabolic, and weight-loss benefits. In this large observational study, GLP-1 receptor agonists were associated with a lower incidence of obesity-related cancers than insulin or sulfonylureas, but the findings do not justify selecting therapy specifically to prevent cancer.

Obesity and type 2 diabetes are associated with increased risk for several cancers. As use of GLP-1 receptor agonists continues to expand, clinicians and patients increasingly want to know whether these therapies influence long-term cancer risk beyond their established metabolic and cardiovascular benefits.

In this target-trial emulation using electronic health record data drawn from a source population of nearly 360,000 adults at UT Southwestern Medical Center, investigators compared initiation of a GLP-1 receptor agonist with metformin, insulin, sulfonylureas, SGLT2 inhibitors, or DPP-4 inhibitors in adults with type 2 diabetes. Patients were followed for up to 5 years for development of an obesity-related cancer. Baseline diabetes severity was categorized as low, moderate, or high based on the presence of complications.

At 3 years, patients starting a GLP-1 receptor agonist had a 38% lower relative risk of obesity-related cancer than those starting insulin and a 33% lower relative risk than those starting sulfonylureas. Absolute differences were modest, with about 1 fewer cancer case per 100 patients treated over 3 years in each comparison.

Results were similar at 5 years. Obesity-related cancer risk remained approximately 39% lower with GLP-1 receptor agonists than with insulin (about 1.7 fewer cases per 100 patients) and 25% lower than with sulfonylureas.

In contrast, cancer incidence was generally similar between GLP-1 receptor agonists and metformin, SGLT2 inhibitors, or DPP-4 inhibitors. The apparent benefit was most evident among patients with less severe diabetes, while findings were less consistent in patients with advanced complications.

The authors noted that the data came from a single health system, that insulin is often initiated later in the disease course, and that residual confounding may remain despite efforts to balance groups. As an observational study, the findings identify where associations were most apparent but cannot establish whether GLP-1 receptor agonists directly reduce cancer risk.

“These findings were broadly reassuring regarding oncologic safety but did not support selecting glucose-lowering therapy for cancer prevention; established metabolic, cardiovascular, and kidney benefits should continue to guide treatment,” wrote the authors, led by Jesús Gibran Hernández-Pérez, PhD, MS, of UT Southwestern Medical Center.

Source: Hernández-Pérez JG, et al. (2026 Nov 3) JAMA Network Open. GLP-1 receptor agonists and obesity-related cancer by diabetes severity