P4823 - Risk of Neuroendocrine Neoplasms With Glucagon-Like-Petide-1 Receptor Agonist Use in Patients With Type 2 Diabetes Mellitus

Gordon Hong, MD¹, Dipen C. Patel, MD², Abbinaya Elangovan, MD³, Bhavana Konda, MD, MPH², Raj Shah, MD², Vineeth Sukrithan, MD²
1University Hospitals Cleveland Medical Center, Case Western Reserve University, Cleveland, OH; 2The Ohio State University Wexner Medical Center, Columbus, OH; 3Virginia Tech Carilion School of Medicine, Roanoke, VA

Introduction: Prior studies demonstrate reduced risk of several malignancies among patients with type 2 diabetes mellitus (T2DM) prescribed glucagon-like-peptide-1 receptor agonists (GLP-1RA). A recent study however found expression of GLP-1R among neuroendocrine neoplasm (NEN) cell lines and growth promotion in xenografts treated with semaglutide. In this study, we evaluate incidence of NENs among patients diagnosed as overweight/obese and patients with T2DM prescribed GLP-1RA based drugs.

Methods: The TriNetX database was utilized for this study. Incidence of NENs between patients with overweight/obesity were compared to a control group without obesity within 15 years following index diagnosis of obesity or, in the control group, a non-specific outpatient visit. Groups were matched for demographics, tobacco use, family malignancy history, alcohol use, and socioeconomic factors. In a separate analysis, incidence of NENs among patients with T2DM were compared between those prescribed GLP-1RAs versus other antihyperglycemic agents (AHA) within 15 years following index prescription of GLP-1RA or comparator AHA. Patients with exposure to the comparator AHA were excluded from their respective groups. A subgroup analysis was performed among patients with overweight/obesity. Exclusion criteria included Merkel cell carcinoma, multiple endocrine neoplasia type 1, Cushing’s syndrome, Von Hippel-Lindau syndrome, tuberous sclerosis, and prior NEN.

Results: Patients with overweight/obesity had a significant increased risk of NENs when compared to the control group (3,840/794,235 (0.48%) vs. 2,785/794,235 (0.35%); RR: 1.38 (95% CI 1.31-1.45), p< 0.0001). Among patients with T2DM, GLP-1RA exposure was associated with significantly lower risk of NENs compared to insulin (70/31,171 (0.23%) vs. 137/31,171 (0.44%); RR: 0.51 (0.38, 0.68), p< 0.0001), but no significant difference was appreciated with other AHAs. In the subset of patients with obesity/overweight, GLP-1RAs were associated with decreased risk compared to insulin (43/15,230 (0.28%) vs. 68/15,230 (0.45%); RR: 0.63 (0.43, 0.93), p=0.02) and metformin (39/10,370 (0.38%) vs. 64/10,370 (0.62%); RR: 0.61 (0.41, 0.91), p=0.01).

Discussion: This study suggests obesity to be significantly associated with incidence of NENs. Furthermore, our findings do not demonstrate an increased incidence of NENs with GLP-RA use among patients with T2DM and show decreased risk when compared to insulin exposure.


Figure: Comparison of incidence of NENs among patients with T2DM that were previously antidiabetic drug-naïve within 15 years of first exposure to GLP-1RAs versus other antihyperglycemic agents. Patients were matched for demographic data (age at index event, gender, race, ethnicity), overweight/obesity, tobacco use, family malignancy history, alcohol use, and socioeconomic factors. Patients with GLP-1RA exposure were at statistically significant decreased relative risk for incidence of NENs when compared to insulin in the overall study population and overweight/obesity population and when compared to metformin in the overweight/obesity population (bolded).

Disclosures:
Gordon Hong indicated no relevant financial relationships.
Dipen Patel indicated no relevant financial relationships.
Abbinaya Elangovan indicated no relevant financial relationships.
Bhavana Konda indicated no relevant financial relationships.
Raj Shah indicated no relevant financial relationships.
Vineeth Sukrithan: Eli Lilly and Company – Grant/Research Support.

Gordon Hong, MD¹, Dipen C. Patel, MD², Abbinaya Elangovan, MD³, Bhavana Konda, MD, MPH², Raj Shah, MD², Vineeth Sukrithan, MD². P4823 - Risk of Neuroendocrine Neoplasms With Glucagon-Like-Petide-1 Receptor Agonist Use in Patients With Type 2 Diabetes Mellitus, ACG 2025 Annual Scientific Meeting Abstracts. Phoenix, AZ: American College of Gastroenterology.