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

Abstract

Background: Evidence regarding the effect of glucagon-like peptide 1 receptor (GLP-1) agonist, when compared with other glucose-lowering drugs, on obesity-related cancer in overweight or obese patients with type 2 diabetes is limited.

Methods: Using Merative Marketscan research databases, we identified all overweight or obese patients with type 2 diabetes aged 20-79 years who received GLP-1 agonist or other glucose-lowering drugs in the United States between January 2016 and June 2021. The primary outcome was obesity-related cancer, defined as a component of 13 cancer types.

Results: Among 919 609 overweight or obese individuals with type 2 diabetes (mean [SD] age = 52.3 [10.9] years; female, 53.5%), 16 653 newly diagnosed with obesity-related cancer were recorded during the 2 086 526 person-years of follow-up. GLP-1 agonist users (vs other glucose-lowering drugs users) were associated with lower incidence (7.5 vs 8.1 per 1000 person-years) and risk of obesity-related cancer (adjusted hazard ratio [HR] = 0.87, 95% confidence interval [CI] = 0.83 to 0.91). This statistically significant association was consistent when comparing GLP-1 agonist with metformin (adjusted HR = 0.90, 95% CI = 0.86 to 0.95), dipeptidyl peptidase-4 inhibitor (adjusted HR = 0.88, 95% CI = 0.84 to 0.93), thiazolidinediones (adjusted HR = 0.84, 95% CI = 0.71 to 0.99), sulfonylureas (adjusted HR = 0.81, 95% CI = 0.74 to 0.88), sodium-glucose transport protein 2 inhibitor (adjusted HR = 0.73, 95% CI = 0.66 to 0.80), and insulin (adjusted HR = 0.70, 95% CI = 0.65 to 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 to 1.10, vs HR = 0.90, 95% CI = 0.84 to 0.97, vs HR = 0.82, 95% CI = 0.77 to 0.88, respectively; Pinteraction = .032).

Conclusions: In a nationwide US cohort of overweight or obese patients with type 2 diabetes, GLP-1 agonist, when compared with other glucose-lowering drugs, was associated with a lower risk of obesity-related cancer, with more pronounced risk reduction with increasing body weight.