Association between glucagon-like peptidase 1 receptor agonist and obesity-related cancer in overweight or obese patients with type 2 diabetes: a nationwide cohort study

Background Evidence regarding the effect of glucagon-like peptidase 1 receptor agonist (GLP-1a), when compared with other glucose-lowering drugs (oGLD), on obesity-related cancer (ORC) in overweight or obese patients with type 2 diabetes (T2D) is limited. Methods Using Merative™ Marketscan® Research Databases, we identified all overweight or obese patients with T2D aged 20-79 years who received GLP-1a or oGLD in the U.S. between January 2016 and June 2021. The primary outcome was ORC, defined as a component of 13 cancer types. Results Among 919,609 overweight or obese individuals with T2D (mean [SD] age, 52.3 [10.9] years; female, 53.5%), 16,653 newly diagnosed ORC were recorded during the 2,086,526 person-years of follow-up. GLP-1a users (vs oGLD users) were associated with lower incidence (7.5 vs 8.1 per 1000 person-years) and risk of ORC (adjusted hazard ratio [aHR] 0.87, 95%CI 0.83-0.91). This significant association was consistent when comparing GLP-1a with metformin (aHR 0.90, 95%CI 0.86-0.95), dipeptidyl peptidase-4 inhibitor (aHR 0.88, 95%CI 0.84-0.93), thiazolidinediones (aHR 0.84, 95%CI 0.71-0.99), sulfonylureas (aHR 0.81, 95%CI 0.74-0.88), sodium-glucose transport protein 2 inhibitor (aHR 0.73, 95%CI 0.66-0.80), insulin (aHR 0.70, 95%CI 0.65-0.76), all P <.05, and was strengthened with increasing weight (overweight, mild-to-moderate, and severe obesity HR 0.95, 95%CI 0.81-1.10 vs 0.90, 95%CI 0.84-0.97 vs 0.82, 95%CI 0.77-0.88; Pinteraction = .032). Conclusions In a nationwide U.S. cohort of overweight or obese patients with T2D, GLP-1a, when compared with oGLD, was associated with a lower risk of ORC, with more pronounced risk reduction with increasing body weight.