(085) An Assessment of Use and Comparative Safety of GLP-1 Receptor Agonists in the Real-world Setting, 2017-2023

Background: GLP-1 receptor agonists (GLP-1RAs), originally approved for use as anti-diabetes treatments, have since been approved for weight management, including in non-diabetic populations. Given the uptake of these products, particularly in non-diabetics, a better understanding of potential safety issues occurring in the real-world setting is warranted

Objectives: To describe the trends and characteristics of new users of GLP-1RAs since 2017 and perform adverse event signal detection using TreeScan™ on U.S. administrative claims data

Methods: We identified new users of GLP-1RAs retrospectively from 2017 through 2023 in U.S. Pharmetrics longitudinal insurance claims data. GLP-1RA indication was derived based on the presence or absence of ICD-10 diagnosis codes proximal to the index GLP-1RA prescription. Patients were categorized as having diabetes only, diabetes and obesity, and obesity only. Trend analyses by class and individual product were conducted for years 2017-2020 and 2021-2023 by indication. Signal detection was performed on GLP-1RA users with obesity only. New GLP-1 users were 1:1 propensity score matched to new users of non-GLP-1 obesity treatments (naltrexone-bupropion, topiramate-phentermine, and orlistat). Using TreeScan™ software for hypothesis-free signal detection, all coding levels of the ICD-10 coding hierarchy were scanned among matched patients. Test statistics in the form of maximum log likelihood ratios (LLRs) were calculated for each node and branch of the ICD-10 coding tree, generating p-values that serve as signaling thresholds (p < 0.05).

Results: Between 2017 and 2020, there were 387,341 new users of GLP-1RAs. Prescriptions were for patients with diabetes only (43.6%) followed by diabetes and obesity (39.1%), and obesity only (9.5%). Between 2021 and 2023, there were 516,125 new users of GLP-1RAs; the most common indications were diabetes and obesity (31.1%), diabetes only (30.9%), and obesity only (23.2%). Users of GLP1-RAs from 2021-2023 were more commonly female compared to users from 2017-2020 (61% versus 55%), which was largely driven by gender differences in use of GLP-1RAs specifically approved for weight management in more recent years. TreeScan identified 9 alerts (p < 0.05), 8 of which were gastrointestinal-related events, including nausea with vomiting (LLR=28.1, p< 0.001), diarrhea (LLR=15.0, p< 0.001), reflux (LLR=10.2, p=0.004), and gastritis and duodenitis (LLR=9.9, p=0.009).

Conclusions: Expanded indications for GLP-1RAs have resulted in different populations of new users in recent years. In non-diabetics using GLP1-RAs for weight management, gastrointestinal-related events were more likely to occur compared to non-diabetics on non-GLP-1RAs weight management products.