RISK OF SEVERE GASTROINTESTINAL EVENTS IN COMMERCIALLY INSURED PATIENTS INITIATING GLP-1RAS FOR DIABETES MELLITUS AND OBESITY: A TARGET TRIAL EMULATION STUDY
Author(s)
Alin Kalayjian, PharmD, MS, Gregory L. Peck, MD, Kamika Reynolds, PhD, Kimberly O’Malley, MS, Chintan Dave, PharmD. PhD;
Rutgers University, New Brunswick, NJ, USA
Rutgers University, New Brunswick, NJ, USA
OBJECTIVES: There is a paucity of data evaluating risk of severe gastrointestinal events for glucagon-like peptide-1 receptor agonists (GLP-1RA) in patients with type 2 diabetes (T2D) and obesity. Given the rapidly expanding use of GLP-1RA across metabolic indications, such data are needed to inform clinical decision-making and benefit-risk evaluations.
METHODS: Using a large U.S. commercial claims database (2017-2022), we constructed four new-user, active-comparator cohorts, including two pairwise comparisons among patients with T2D: Cohort 1a (GLP-1RA vs SGLT2i) and Cohort 1b (GLP-1RA vs DPP4i), and two among patients with obesity: Cohort 2a (GLP-1RA vs bupropion-naltrexone) and Cohort 2b (GLP-1RA vs phentermine-topiramate). The primary outcomes were severe gastrointestinal events, including severe GI hypomotility (gastroparesis and small or large bowel obstruction) and severe gallbladder or biliary tract disorders (e.g., cholecystitis).Hazards ratios [HR] and Incidence Rates [IR} per 1,000 person years were estimated using inverse probability of treatment weights, which adjusted for >100 covariates. Hospitalizations due to pancreatitis were examined as a negative control outcome.
RESULTS: Among patients with T2D in Cohort 1a (N=343,011), GLP-1RA initiation was associated with increased adjusted risks of severe gastrointestinal hypomotility (HR 1.24, 95% CI 1.07-1.42) and gallbladder and biliary tract disorders (HR 1.20 [1.08-1.34]) vs SGLT2i. In Cohort 1b (N=302,123), the corresponding risks vs DPP4i were HR 1.24 (1.07-1.45) and HR 1.06 (0.94-1.19), respectively. In obesity cohorts, GLP-1RA use was associated with higher risks of gastrointestinal hypomotility vs bupropion-naltrexone in Cohort 2a (N=89,916; HR 1.83 [0.96-3.49]) and vs phentermine-topiramate in Cohort 2b (N=80,705; HR 1.09 [0.48-2.48]), and markedly increased risks of gallbladder and biliary tract disorders (HR 1.68 [1.19-2.36] and HR 2.60 [1.33-5.09], respectively). GLP-1RAs did not increase risk of negative control outcome of pancreatic hospitalizations.
CONCLUSIONS: Generalizability is limited to commercially insured populations; initiation of GLP-1RAs was associated with elevated risks of severe gastrointestinal events.
METHODS: Using a large U.S. commercial claims database (2017-2022), we constructed four new-user, active-comparator cohorts, including two pairwise comparisons among patients with T2D: Cohort 1a (GLP-1RA vs SGLT2i) and Cohort 1b (GLP-1RA vs DPP4i), and two among patients with obesity: Cohort 2a (GLP-1RA vs bupropion-naltrexone) and Cohort 2b (GLP-1RA vs phentermine-topiramate). The primary outcomes were severe gastrointestinal events, including severe GI hypomotility (gastroparesis and small or large bowel obstruction) and severe gallbladder or biliary tract disorders (e.g., cholecystitis).Hazards ratios [HR] and Incidence Rates [IR} per 1,000 person years were estimated using inverse probability of treatment weights, which adjusted for >100 covariates. Hospitalizations due to pancreatitis were examined as a negative control outcome.
RESULTS: Among patients with T2D in Cohort 1a (N=343,011), GLP-1RA initiation was associated with increased adjusted risks of severe gastrointestinal hypomotility (HR 1.24, 95% CI 1.07-1.42) and gallbladder and biliary tract disorders (HR 1.20 [1.08-1.34]) vs SGLT2i. In Cohort 1b (N=302,123), the corresponding risks vs DPP4i were HR 1.24 (1.07-1.45) and HR 1.06 (0.94-1.19), respectively. In obesity cohorts, GLP-1RA use was associated with higher risks of gastrointestinal hypomotility vs bupropion-naltrexone in Cohort 2a (N=89,916; HR 1.83 [0.96-3.49]) and vs phentermine-topiramate in Cohort 2b (N=80,705; HR 1.09 [0.48-2.48]), and markedly increased risks of gallbladder and biliary tract disorders (HR 1.68 [1.19-2.36] and HR 2.60 [1.33-5.09], respectively). GLP-1RAs did not increase risk of negative control outcome of pancreatic hospitalizations.
CONCLUSIONS: Generalizability is limited to commercially insured populations; initiation of GLP-1RAs was associated with elevated risks of severe gastrointestinal events.
Conference/Value in Health Info
2026-05, ISPOR 2026, Philadelphia, PA, USA
Value in Health, Volume 29, Issue S6
Code
CO86
Topic
Clinical Outcomes
Topic Subcategory
Comparative Effectiveness or Efficacy
Disease
SDC: Diabetes/Endocrine/Metabolic Disorders (including obesity), SDC: Gastrointestinal Disorders