Understanding GLP-1 Agonists: Key Insights for Payers

By: Emily Crisano, PharmD, RPh, and Jason Peterson, RPh

The rapid adoption of GLP-1 treatments underscores their significance in modern therapeutic practices, making it imperative for payers, healthcare providers and consumers to stay informed about their evolving uses and market dynamics. 

What is a GLP-1? 

GLP-1, or glucagon-like peptide-1, is a hormone from the small intestine released when we eat. Its receptors, found in the pancreas, stomach, kidney, heart, lungs, skin, immune cells, and hypothalamus, stimulate insulin release, slow stomach emptying, inhibit post-meal glucagon release, and reduce food intake. These effects help manage type 2 diabetes (T2D) and obesity. 

Current GLP-1 Products and Uses 

The current market for GLP-1 agonists primarily consists of several key medications primarily indicated for the treatment of T2D or obesity. 

Semaglutide 

Semaglutide is currently approved as three separate products, all developed and manufactured by Novo Nordisk.  

1. Rybelsus is taken orally once daily, while Ozempic is administered once weekly.  

2. Ozempic also has FDA approval to reduce the risk of major adverse cardiovascular events (MACE) in adults with type 2 diabetes and cardiovascular disease.  

3. Wegovy, also given once weekly, was first approved in 2021 for weight loss in adults with obesity. Since then, Wegovy has gained additional approvals for use in pediatric patients aged 12 and older with obesity and to reduce the risk of MACE in adults with established cardiovascular disease who are overweight or obese. 

Tirzepatide 

Tirzepatide, developed by Eli Lilly, is available on the market under two brand names:  

1. Mounjaro is FDA-approved for use in conjunction with diet and exercise to improve glycemic control in adults with T2D.  

2. Zepbound is FDA-approved for use in conjunction with a reduced-calorie diet and increased physical activity for obesity. 

Liraglutide 

Also manufactured by Novo Nordisk, liraglutide is currently available as: 

1. Victoza, given once daily by subcutaneous injection, is indicated for use with diet and exercise to improve glycemic control in pediatric patients at least 10 years old and adults with T2D. It also has been approved to reduce the risk of MACE in adults with T2D and cardiovascular disease. 

2. Saxenda, also a once daily injection, is approved for weight loss in children at least 12 years old and adults diagnosed with obesity. 

Dulaglutide 

Eli Lilly’s dulaglutide entered the market as a once-weekly injectable GLP-1 agonist: 

• Trulicity is indicated for use with diet and exercise to improve glycemic control in pediatric patients at least 10 years old and adults with T2D. Trulicity has also been approved to reduce the risk of MACE in adults with T2D and cardiovascular disease. 

Exenatide 

Exenatide was the first GLP-1 to enter the market in 2005. Both drugs in this category are currently manufactured by AstraZeneca: 

1. Byetta is a twice daily injection for use with diet and exercise to improve glycemic control in adults with T2D.  

2. Bydureon BCise, an extended-release version which can be injected once weekly, is approved for use in pediatric patients at least 10 years old and adults with T2D.   

The Introduction of Generics 

On June 22, 2024, Teva launched an authorized generic for Victoza (liraglutide) at a 13.6% discount. This followed the FDA's tentative approval of the first traditional generic by Hikma Pharmaceuticals. An authorized generic is an unbranded product made by the brand name company.  

Hikma’s version will likely be priced much lower than the authorized generic and there is anticipation of at least six more generic manufacturers entering the market within the next one to two years. More generic competition should continue to drive prices down. 

Expanding Pipeline 

The GLP-1 pipeline is rich with new indications for existing FDA approved drugs as well as new market entrants. Below is a list of products in Phase III and/or Phase II clinical trials which have high potential for approval.  

Exploring Additional Biochemical Mechanisms 

Beyond GLP-1s, researchers are studying the following drugs and their respective mechanisms of action within the body. The pathways below are being leveraged along with GLP-1s in the clinical development of products that have dual and sometimes triple agonistic (or activation) effects. 

• GIP Agonism: 

  • Reduces appetite, nausea, and bone resorption 

  • Increases insulin & glucagon production, and lipogenesis  

• Glucagon Agonism: 

  • Reduces appetite, food intake, and gastric emptying 

  • Increases insulin production, energy expenditure, and nausea 

• Amylin Agonism: 

  • Reduces appetite, food intake, glucagon production, and gastric emptying 

  • Increases energy expenditure 

  • Reduces bone resorption and increases bone production 

• PYY Agonism: 

  • Reduces appetite, food intake, and gastric emptying 

  • Increases energy expenditure and nausea 

The Cost Challenge for Payers 

The cost of GLP-1s continues to be a significant concern for payers between skyrocketing costs and utilization over the past several years. Weight loss treatments currently demand the highest prices, with monthly Wholesale Acquisition Costs (WAC) between $1,060 and $1,350. Treatments for type 2 diabetes have monthly WACs ranging from $827 to $977. 

Eli Lilly and Novo Nordisk dominate the GLP-1 market, and most payers secure access through competitive rebate contracts, offering discounts of 35%-50%. This brings the net cost to about $400 to $800 per month. However, GLP-1s remain more expensive than insulin, which now costs payers $90 to $200 per month due to recent price drops. 

Payer Considerations 

PBMs and health plans continue to review and debate this growing therapeutic class, trying to find the most viable path forward. Key areas of concern for decision makers and executives include: 

Continued rapid rates of increased utilization: 

• Treatment guideline recommendations to prefer GLP-1 agonists and GIP/GLP-1 dual agonists over other less expensive diabetic treatments 

• Increase in physicians’ awareness of obesity as a disease 

• Stronger trust in the long-term effects and safety of GLP-1 receptor agonists 

• Unwavering demand by individuals seeking quick weight loss solutions 

Additional products seeking approval and entering the market: 

• Over 50 products are currently in clinical development for obesity and/or T2D 

• GLP-1 agonism is being studied in combination with other mechanisms of action including GIP agonism, glucagon agonism, amylin agonism, and PYY agonism 

• Shortages of currently marketed drugs provide opportunity for additional products to successfully enter the marketplace 

Additional indications for these products are gaining approval: 

• Clinical trials are ongoing for several indications beyond the currently approved obesity and/or T2D uses 

• Examples of therapeutic applications currently under investigation include Parkinson’s and Alzheimer’s diseases, smoking cessation, alcoholism, and MASH 

The GLP-1 agonist market is rapidly evolving with significant implications for payers. As new products and indications emerge, and generic competition increases, the potential for cost savings and improved patient outcomes grows. Payers must stay informed and agile, leveraging competitive contracts and exploring new therapeutic opportunities to manage costs and provide access to these life-changing therapies.  

References

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