Expanding indications for GLP-1s (2024)

It’s official: The popular weight loss drug Wegovy isn’t just for weight loss anymore. Its recent FDA approval to help reduce the risk of cardiovascular (CV) events in certain patients is likely just the beginning of expanding indicationsfor GLP-1s.

As the clinical landscape evolves, there’s an appetite to better understand what is driving the therapeutic effects of these drugs, what additional indications are expected, and what the cost impact might be for plan sponsors in the long term.

30M Americans may be using GLP-1s by 2030 – 9% of the population1

What we know – and what we’re still learning – about how GLP-1s work

GLP-1s – the common term for glucagon-like peptide 1 receptor agonists, including GIP/GLP-1s, which also target glucose-dependent insulinotropic polypeptide receptors – mimic incretin hormones in the body. This action effectively decreases blood glucose by stimulating the release of glucose-dependent insulin.

GLP-1s also inhibit glucagon secretion and slow the time it takes for stomach contents to empty into the intestines. The delay in gastric emptying creates a feeling of fullness that lasts longer. That, in combination with effects on the brain that suppress appetite, contributes to weight loss, as well as helping control type 2 diabetes. Less is known about how GLP-1s work on other body systems or if their metabolic health benefits are the driving factor in treating other conditions.

For instance, does Wegovy help reduce the risk of CV events because weight is a factor in cardiac health, or might other physiological mechanisms be at work? Researchers are beginning to zero in on some theories. One that has gained traction is that GLP-1s also help reduce cardiovascular inflammation. This may occur because the drugs can cause increases in nitric oxide production, which may have some effect on vascular pathways.2,3

The robust GLP-1 pipeline

As we learn more about how GLP-1s work, we expect to see the development of newer GLP-1 agents – or combinations – that may be more effective, produce fewer adverse reactions, and offer easier administration, such as in pill form instead of injection. We could also see them gain approval to treat a myriad of health conditions, including:

Metabolic dysfunction-associated steatohepatitis (MASH), also known as non-alcoholic fatty liver disease. Studies have shown that GLP-1s directly affect the liver on glucose production. It is also thought that as the drug breaks down in the body, it helps minimize fat build-up.4
Neurological disorders, including Alzheimer’s and Parkinson’s disease. GLP-1s may help protect nerves and preserve brain function, which may help slow the progression of these conditions and improve symptoms.5
Diabetic retinopathy, a complication of diabetes that affects vision. In addition to lowering body weight, blood glucose, and lipid levels, GLP-1s may also improve retinal thickness and shape, as well as the structure for blood flow.6
Sleep apnea. A recent clinical trial found that the GIP/GLP-1 tirzepatide significantly reduced sleep apnea severity.7 While weight loss likely is a factor, the potential for GLP-1s to decrease systemic inflammation may help, too.8
Substance use disorders. GLP-1s may be effective in curbing smoking and alcohol consumption by activating dopamine receptors in the brain, although additional research is still needed.9 They may also impact nicotine receptors, suggesting multiple pathways of efficacy.10

Cost considerations for payors

With all this and more in the pipeline, we anticipate the market could change significantly over the next few years. As payors refine their coverage strategies for weight management GLP-1s, there will be a lot of variable factors to consider, including marketplace dynamics that likely will cause prices to fluctuate.

The eventual availability of generics, while likely still years away, will come into play, as will the resolution of current drug shortages.11 Newer clinical guidelines could affect prescribing patterns. There likely will be overlap in the patients these agents are prescribed for, which could be a factor in overall drug spend. Patients with sleep apnea, for instance, are likely to have obesity. And regulatory shifts could affect coverage requirements in this class.

It will also be important to pay attention to patient attrition patterns. Current research shows that many people discontinue GLP-1 therapy on their own for various reasons, including lack of insurance coverage or inability to pay high out-of-pocket costs, especially for those with high-deductible health plans.12 Others may cease therapy due to unmanageable side effects, injection fatigue, or because their weight loss has plateaued.13,14 Or they may be unable to fill their prescriptions due to shortages. Understanding why patients discontinue therapy and the costs associated with the effects of stopping could be an important part of the larger picture of your GLP-1 strategy.

As your trusted PBM partner, CVS Caremark is uniquely positioned to help you evaluate how factors such as these may affect your bottom line and your overall pharmacy spend, as new agents and indications gain approval. We can helpdevelop a coverage, cost, and care strategy that meets your needs in the changing market.

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