GLP-1 and GLP-1/GIP for Obesity Management

Obesity is a common, serious, and costly disease. If patients do not respond to lifestyle management, medication therapy, devices and surgery can be considered. Medications for weight loss are not new; however the effectiveness of newer weight loss medications has driven a new conversation on this topic.

Glucagon-like peptide-1 (GLP-1) receptor agonists are available as single agents and in combination with gastric inhibitory polypeptide (GIP) and are FDA approved for the treatment of type II diabetes and obesity/weight loss. The current wholesale acquisition cost (WAC) of weight loss GLP-1s and GLP-1/GIPs have made these medications budget busters throughout the country. News reports are emerging of states, health systems and employers who previously provided coverage for weight loss agents but have had to pull back or stop coverage.

It is estimated that the global GLP-1 and GLP-1/GIP market was $36.8 billion in 2023 with a projected growth to $138 billion by 2031 across diabetes and obesity indications. In 2023, the weight loss medications accounted for $9.3 billion (25%) of this cost, but this percentage split will continue to shift towards obesity if utilization trends continue.

GLP-1 and GLP-1/GIPs continue to be the focus of media and social media as well as conversations with plan sponsors around their spend. Wasteful spending due to high rates of discontinuation has been noted in studies and the real world. Studies and real-world experience have also shown that once stopped, weight is regained putting these agents in the category of chronic medications.

Fall 2024 Updates

Adverse Drug reactions

Like any prescription drug, these agents come with risk. While gastrointestinal side effects have been known, as these agents are used by a larger population and for a longer period, new concerns have arisen. While they may not impact all, consideration needs to be given to the more severe GI side effects such as intestinal blockage and gastroparesis. In addition, the impact of these therapies and the ensuing weight loss on muscle and bone is of concern.

Additional safety concerns have been raised with the use of compounded medications. The risks are not centered on the actual agent. There have been issues with the prescription, compounding, and patient use that have led to hepatizations.

Data

In late 2023, the results of the long anticipated SELECT trial were released and showed some positive benefit to the use of GLP-1s in patients without diabetes. In this study, patients 45 years or older who had already experienced a cardiovascular event had a 1.5% lowering of additional events. The outcomes of the SELECT trial led to a new FDA approval for Wegovy in March of 2024. The medication received an indication for preventing cardiovascular disease in patients with obesity or for those who are overweight and have existing cardiovascular disease.

It is important to truly assess what the information is saying. In the SELECT trial, the study population was those age 45 years and older who had previously had a cardiovascular event such as heart attack, stroke, or symptomatic PAD with objective tests. This patient population is important to keep in mind as this cardiovascular impact cannot be expanded to those without these specific previous disease states.

When assessing studies like this, there is an important factor to consider, and that is the number needed to treat. In this case, based on the number needed to treat, it would cost over $2 million, after rebates, to prevent one additional cardiovascular event. Contrasting that with GLP-1s in patients with diabetes, it costs around $650,000 to prevent one additional cardiovascular benefit.

Generic Pipeline

Victoza (liraglutide) generic first launched with an authorized generic in June 2024. While an authorized generic does not drive the price down significantly, there is the potential for ten true generics to the market starting in December 2024. This additional competition is anticipated to bring some pricing relief.

While pricing relief for liraglutide is a great outcome, it is anticipated to have little impact on the GLP-1 and GLP-1/GIP market. Due to its daily dosing and smaller impact, liraglutide is one of the least utilized GLP-1 for diabetes management with 4.6% of the market share. The same is true for obesity. Branded liraglutide, Saxenda, is not anticipated to have a generic approved until at least 2027 and off label use of the current liraglutide is not anticipated to impact the obesity space as the weight loss is less than 50% of that with Wegovy and Zepbound. In addition, higher doses of generic liraglutide for diabetes would need to be used to achieve this impact leading to doubling of the generic cost erasing much of the savings.

Wegovy and Zepbound generics are not anticipated until at least 2035 or 2036 leaving brand names cost for time to come. While the hope is that more GLP-1 and GLP-1-/GIP on the market will drive down cost with competition, the impact and timeline remain to be seen.

Indication Pipeline

Due to the success of GLP-1 and GLP-1/GIP medications to date, the pipeline of future treatment is strong. Additional medications in the same classes today are close to approval, including oral semaglutide for obesity. Despite positive study results, the manufacturer has not yet commented on the timeline for approval. New agents are also being explored including adding additional agents to GLP-1/GIP and bring triple-therapy medications to market.

In addition to new agents, the use of GLP-1 and GLP-1/GIP medications is expected to expand past diabetes and weight loss in the coming years. Ongoing studies are looking at the use of these agents in other disease states. If GLP-1s and GLP-1/GIPs are approved for additional disease states, the impact of increased use of these medications will further impact pharmacy plan spend.

GLP-1s are being studied from manufactures for a variety of disease states including sleep apnea, non-alcoholic steatohepatitis (NASH), kidney disease, heart failure, Alzheimer’s disease, dementia, and knee osteoarthritis. Sleep apnea is the closest to expansion with Eli Lilly submitting for FDA approval for tirzepatide. This approval review is anticipated still in 2024. Except for Alzheimer’s and dementia, these conditions have one thing in common, obesity tends to be a contributing factor. Regarding NASH, this is a disease state were GLP-1, and GLP-1/GIP medications can lead to cost savings. The currently approved treatment for NASH, Rezdiffra, has an annual WAC of $48,000.

In addition to manufacturer trials that can lead to expanded indications, data continues to be shared from others regarding additional disease states such as addiction, nicotine use, polycystic ovary syndrome, and peripheral arterial disease.

Just as GLP-1 and GLP-1/GIPs have had a financial impact on diabetes and obesity, they are anticipated to grow spending once approved for other disease states. They are also expected to impact the Alzheimer’s market with spending growth from $4.8 billion to $8.18 billion by 2032 and the NASH market with spending growth from $1.62 billion to $24.2 billion by 2028.

Recommendations

Today, the majority of plan sponsors continue to not provide coverage for GLP-1s for weight loss. Not only that, but the reports of plan sponsors ending coverage because of the inability to afford the increase continue to hit the news. If a plan sponsor does elect to provide coverage, it is vital that they have controls for accountability in their approach.

Accountability actions can include the requirement to work with a health coach or behavioral specialist, the requirement for weight loss to continue to receive the medications, and limits on refills. Prior authorization should be a given with adherence monitoring to ensure patients are taking as prescribed to not use the medication in a wasteful manner.

Plan sponsors who do choose to cover can also get creative in their coverage for potential savings by offering to a smaller population group. One such example is covering for those with a higher BMI, such as grade 3 obesity (BMI > 40 kg/m²). They may also choose to limit access to those enrolled in specific programs or working with specific providers. Some of these actions may impact rebates, in turn, impacting the net cost of these agents. Regardless of the decisions made, it is important to have an unbiased assessment done of the overall cost and/or savings of these decisions.

At Innovative Rx Strategies, we continue to monitor the latest news on GLP-1s and can help plan sponsors identify how to respond to this class of therapies. If you have any questions, don’t hesitate to reach out to one of our pharmacists.