(B-063) Off-label Use of Glucagon-like Peptide 1 Agonists (GLP-1): Evidence from Medicare Part D

Background: The rising use of Glucagon-like peptide-1 receptor agonists (GLP-1s) and the current restriction on Medicare's coverage of these drugs for cosmetic purposes may encourage off-label prescribing of diabetic products to treat obesity, particularly following general recognition of weight loss magnitude. However, the extent of such practice is unclear. Understanding the extent of off-label GLP-1s prescribing has implications for policy and spending.

Objectives: To identify possible off-label prescribing of GLP-1s in Medicare Part D from 2019-2023.

Methods: This cross-sectional study included Medicare beneficiaries enrolled in Part D who initiated semaglutide or tirzepatide between 2019 and 2023 from a 20% sample of Traditional Medicare (TM) claims. Part D data was used to identify new GLP-1 users. We defined possible off-label use as the absence of a diabetes diagnosis or a prescription history of non-GLP-1 diabetes medications within one year before or six months after their first fill. A diabetes diagnosis was defined as: (1) having more than two diagnosis records in TM claims (outpatients, inpatients, carriers, and home health agencies) on different dates; or (2) having a diabetes indicator (DIABETES) in the Master Beneficiary Summary File Chronic Conditions. We used descriptive statistics to characterize the possible off-label prescription of GLP-1s and a quasi-experimental approach to address measurement error and provide the best estimates of off-label use to date. We examined the differences in the proportion of off-label use in new users between GLP-1 users and insulin users using difference-in-difference with year fixed effect. The intervention is the release of favorable clinical evidence on the weight loss effect of GLP-1s, which was in the first quarter of 2021 (1Q21).

Results: Among 165,250 new users of GLP-1s in Medicare between January 2019 and June 2023, 16,562 (10.0%) were identified as possible receiving the drug off-label. Off-label use has increased over time from 1.8% of new users in 2019 to 15.0% in the first half of 2023. Possible off-label users are more likely to be obese, younger, female, white, pay more out-of-pocket, and have better adherence in the six months after their initial fill. Difference-in-differences estimates suggest a 6.06 percentage point increase in off-label prescribing after 1Q21 (95% CI: 2.82%–9.29%).

Conclusions: Our findings indicate off-label use of GLP-1s among TM beneficiaries increased substantially from 2019 through 2023. This growth, especially following general recognition of weight loss magnitude, underscores significant current and future budget implications for Medicare, particularly amid active policy discussions about explicitly extending coverage of GLP-1 medications for weight management.