Current Landscape Overview

Glucagon-like peptide-1 (GLP-1) receptor agonists (RAs) are an emerging drug class that are mostly indicated to improve glycemic control in patients with type 2 diabetes mellitus (T2D) and reduce body weight. For the GLP-1 RA products approved for glycemic control in T2D, some have expanded use to younger patients, and/or in additional at-risk comorbid adult populations. For branded products approved to reduce weight in obesity, some also have expanded use to younger patients, and/or additional at-risk adult populations. To date, one brand has not differentiated itself in all areas, which has opened the door for future evidence development. Additionally, as products expand their indications, focus is on not only the diagnoses of the populations, but also the action/effect of the GLP-1 product on disease pathophysiology. For specific alignment of comparison of FDA indications, see Table 1.

Table 1. Differentiation in GLP-1 Products   

*Weight-related comorbidities may include but are not limited to hypertension, dyslipidemia, CVD, sleep apnea, and T2D. CKD: Chronic Kidney Disease; CVD: Cardiovascular Disease

Although several in-line GLP-1 and glucose-dependent insulinotropic polypeptide (GIP)/GLP-1 RAs have approved indications beyond T2D and overweight/ obesity, US Pharmacopeia Drug Classification (USP DC) 2025 limits classification to categories/classes according to their primary diagnosis (e.g., antidiabetic; anti-obesity). This has downstream impacts on coverage of drugs by non-Part D plans that use USP classifications when designing their formularies. Manufacturers interested in expanding the number of USP DC categories and/or classes their product is on should submit additional evidence linking its mechanism of action to additional indications.

While currently approved GLP-1 and GIP/GLP-1 RAs have multiple on-label indications, many of them are also used off-label. To further explore on- and off-label use of these drugs, Avalere Health evaluated 2018–2023 commercial (42% population sample), Medicare fee-for-service (FFS) (100%), Medicare Advantage (25%), and Managed Medicaid (69%) pharmacy claims data to identify beneficiaries with a pharmacy drug claim for GLP-1 and/or GIP/GLP-1 RAs. FDA-approved labels were used to determine on- and off-label use.

GLP and GIP/GLP-1 RAs had 88% on-label use and 12% off-label use (Figure 1), which was consistent with uses at the brand level. In recent years, off-label use for weight loss has contributed to GLP-1 RAs shortages, limiting access for patients with diabetes.

Figure 1. On- and Off-label Use of GLP-1 and GIP/GLP-1 RAs*

*GLP-1 and GIP/GLP-1 RAs include: Bydureon, Byetta, Victoza, Ozempic, Rybelsus, Adlyxin, Saxenda, Wegovy, Zepbound, Trulicity, Mounjaro; **Overlap in beneficiaries is possible if beneficiaries switched insurance types over time.

Current Pipeline

The current pipeline for GLP-1 RAs is robust with 1,465 clinical trials in various stages. While the majority of these studies focus on T2D, other conditions of interest include CVD, overweight/obesity, T1D, endocrine disorders associated with insulin metabolism.

The pipeline for dual RAs, such as GIP/GLP-1 RAs, is much less robust with, only 27 clinical trials in Phase 1–Phase 4. These dual RAs are being evaluated mainly in T2D, T1D, overweight/obesity, and few other possible indications (Figure 2). Manufacturers may expect significant levels of competition, specifically within the GLP-1 RA class, and will need to differentiate their assets and value proposition to remain competitive and maintain and/or grow their market share.

Figure 2. GLP-1 and GIP/GLP-1 RAs Pipeline

Source: clinicaltrials.gov

Value Differentiation and Connection to Coverage

New entrants to this crowded market will need to differentiate themselves through a strong payer value story that spans beyond T2D, overweight/obesity, CVD indications. In addition, both new and established manufacturers in this space should consider studying additional indications to further differentiate themselves from current or future competitors. A strong value proposition will have downstream impacts on securing favorable coverage and formulary placement, which will be addressed in our next insight.

Data Source

For this analysis, Avalere used commercial and Managed Medicaid claims data from Inovalon’s proprietary “Medical Outcomes Research for Effectiveness and Economics” (MORE2) Registry®, accessed by Avalere via an Agreement with Inovalon, Inc. Avalere also utilized the 100% Medicare FFS claims, accessed by Avalere via a research collaboration with Inovalon, Inc. and governed by a research-focused CMS Data Use Agreement (DUA).