Expanded Indications and Future Outlook for GLP-1 Medications

GLP-1 medications, originally developed for type 2 diabetes management, are being studied for a variety of potential future uses beyond their current indications. GLP-1, also known as glucagon-like peptide-1 receptor agonists, is a naturally occurring hormone in the body that helps regulate blood sugar levels. It works by:

• Stimulating insulin release from the pancreas.
• Slowing gastric emptying, which slows the rate at which food moves from the stomach into the small intestine.
• Promoting satiety by acting on the brain to increase feelings of fullness and reduce appetite, leading to decreased food intake.

In addition to these well-known mechanisms, other potential benefits are currently being studied.

Cardiovascular Indication

One of the significant advancements is the expanded indication for Wegovy (semaglutide). In March 2024, the FDA approved a new

indication for Wegovy to reduce the risk of major adverse cardiovascular (CV) events, such as heart attack and stroke, in adults with established cardiovascular disease who are either overweight or obese. This approval means that Wegovy, along with a reduced-calorie diet and increased physical activity, can help this specific patient population lower their risk of serious heart problems.

This expanded indication makes sense, as obesity is a risk factor for many complications, including cardiovascular disease. Weight loss, which Wegovy has been proven to promote significantly, is a known factor in reducing cardiovascular risk. Beyond weight loss and glycemic control, GLP-1 medications may reduce CV risk by improving blood pressure and cholesterol levels, reducing inflammation, atherosclerotic plaques and oxidative stress.

Promising Areas of Research

Research into GLP-1 medications has expanded into several promising areas, including:

1. Non-alcoholic fatty liver disease (NAFLD): Studies have shown that GLP-1 medications can help improve liver function and reduce fat storage in the liver.
2. Neurodegenerative diseases: There is potential for GLP-1 medications to protect brain cells and improve cognitive function, with neuroprotective effects that may help reduce inflammation and oxidative stress.
3. Polycystic ovary syndrome (PCOS): GLP-1 medications may help improve insulin sensitivity and regulate ovulation in women with PCOS.
4. Diabetes prevention: GLP-1 medications are being studied for their potential to prevent the onset of type 2 diabetes in high-risk individuals.
5. Gastrointestinal disorders: Conditions such as irritable bowel syndrome (IBS) and inflammatory bowel disease (IBD) are being researched for potential treatment with GLP-1 medications.
6. Psychiatric disorders: Preliminary studies are looking at the impact on mood disorders and cognitive function, given the growing understanding of the gut-brain axis and metabolic influences on mental health.
7. Chronic kidney disease (CKD): Research is assessing the benefits of GLP-1 medications in slowing the progression of kidney disease and improving renal function in patients with CKD.

Future Coverage Outlook

The future of insurance coverage for GLP-1 medications is uncertain with various challenges ahead.

Arguments in Support of Increased Coverage

There is strong evidence regarding the benefits of GLP-1 medications, as they demonstrate significant advantages beyond diabetes control, including weight loss and potential cardiovascular disease prevention, which could be seen as cost-effective by insurers. Patient advocacy is also gaining momentum, with growing demand for access to these medications, especially for weight management, could push for broader insurance coverage. Additionally, clinical evidence and guidelines play a critical role, as endorsements from major health organizations (e.g., American Diabetes Association, American Heart Association) can drive broader coverage based on clinical efficacy. Lastly, ongoing new research into other potential uses of GLP-1 medications could strengthen the value proposition for insurers.

Challenges Against Increased Coverage

Despite the potential benefits of GLP-1 medications, several challenges may create an obstacle to increased coverage. The current high cost of GLP-1 medications presents a financial burden for insurers. Additionally, an ongoing debate regarding obesity vs. diabetes persists with some insurers potentially hesitating to cover GLP-1 medications solely for weight loss, especially given the current lack of coverage for obesity medications in the ACA Marketplace. Furthermore, there is a need for clearer guidelines from medical organizations on how and when to prescribe GLP-1 medications, as this could help insurers establish consistent coverage policies.

Possible Future Scenarios

As the landscape of GLP-1 medication coverage evolves, there are several scenarios that insurers may follow. Some insurance companies may implement tiered coverage with higher copays or stricter prior authorization requirements for GLP-1 medications used for weight loss compared to those used for diabetes or cardiovascular disease prevention. Another possible scenario is a focus on evidence-based use, where coverage may become more focused on specific patient populations with strong evidence of the benefits, such as those with both obesity and diabetes. We may also see more negotiations and cost-sharing as increased negotiations between insurers, pharmaceutical companies, and patient groups may make GLP-1 medications more affordable and accessible. More specific scenarios include the following:

• Current Coverage Rules for Weight Loss: Current coverage rules for weight loss typically require 1) engagement in a trial of behavioral modification and dietary restriction for at least three months, 2) a baseline BMI of >30 or >27 with comorbidities and 3) medication use in conjunction with behavioral modification and a reduced-calorie diet. These requirements aim to ensure that the medication is used as part of a comprehensive weight management approach rather than as a standalone solution.
• Custom Copay Structure: Some insurers are considering implementing a separate copay structure for specific drugs or classes of While this approach could provide more flexibility in coverage, it could potentially impact manufacturer rebates.
• Maximum Allowable Benefit: The possible implementation of annual or lifetime benefit caps on weight loss drugs is as also another consideration as a cost-saving However, this approach faces a counterargument as studies show that stopping the medication often results in weight regain. This creates a challenging dilemma for insurers trying to balance cost management with long-term health outcomes.
• More Stringent Utilization Management: More stringent utilization management approaches are also under This includes developing higher BMI requirements by pharmacy benefit managers (PBMs) and a“risk-managed” approach focusing on high-risk CV comorbidity, BMI >35, prior trials of non-GLP-1 medication for obesity and use as part of a weight loss program.

Ultimately, the actual coverage of GLP-1 medications will depend on ongoing clinical evidence, cost-effectiveness analyses and evolving healthcare policies.

Sources:

Mechanisms of GLP-1. Drucker, D. J. “Mechanisms of Action and Therapeutic Application of Glucagon-like Peptide-1,” Cell Metabolism, 27(4), 740-751, 2018.

Wegovy and Cardiovascular Indications. Press Release. “FDA Approves Wegovy® for Cardiovascular Risk Reduction in Adults with Established Cardiovascular Disease,” Novo Nordisk. (2024).

Further Research:

• Sharma, D., Verma, S., & Vaidya, S. Therapeutic potential of GLP- 1 Analogs in Non-Alcoholic Fatty liver Disease. Biomedicine & Pharmacotherapy, 123, 109732, 2020.
• Hölscher, Central effects of GLP-1: New opportunities for treatments of neurodegenerative diseases. Journal of Endocrinology, 246(1), R1- R15, 2020.
• Løvdal Gulseth, H., & Gjesing, A. P. GLP-1 Analogs in the Treatment of Polycystic Ovary Syndrome: An Overview. Journal of Clinical Endocrinology & Metabolism, 106(5), 1246-1257, 2021.
• Meier, J. GLP-1 Receptor Agonists for Individualized Treatment of Type 2 Diabetes Mellitus. Nature Reviews Endocrinology, 17(8), 450-466, 2021.
• Drucker, J. (2016). The Role of Gut Hormones in Metabolic Regulation. Journal of Clinical Investigation, 126(1), 390-398.
• Bethel, A., et al. Effects of Glucagon-Like Peptide-1 Receptor Agonists on Kidney Outcomes in Type 2 Diabetes: A Meta-Analysis of Randomized Trials. The Lancet Diabetes & Endocrinology, 6(1), 29-39, 2018.

Insurance Coverage and Future Outlook:

• American Diabetes “Standards of Medical Care in Diabetes—2022. Diabetes Care, 45(Suppl 1), S1-S264,” 2022.
• American Heart 2023 AHA/ACC Guideline for the Management of Patients with Chronic Stable Angina, 2023.
• Tran, K., et al.). The economic impact of GLP-1 receptor agonists in the management of type 2 diabetes. Journal of Managed Care & Specialty Pharmacy, 27(10), 1387-1395, 2021.