GLP-1s and Obesity Care: Cardiorenal Outcomes, Prescribing Considerations, and Access Barriers

In 2005, the FDA approved exenatide (Byetta; Amylin Pharmaceuticals/Eli Lilly), the first glucagon-like peptide-1 receptor agonist (GLP-1 RA), for the treatment of type 2 diabetes. Exenatide activates the GLP-1 receptor, which is found in the pancreas and brain, helping to regulate blood sugar, appetite, and digestion.¹

Over the past 20 years, additional GLP-1–based therapies have been approved, and the class has become a mainstay of type 2 diabetes treatment with a favorable benefit-risk profile compared with many other glucose-lowering medications.² Because GLP-1 RAs mimic a natural gut hormone that slows digestion, increases feelings of fullness, reduces appetite, and improves insulin function, several have since been approved for weight management in patients with obesity.

Obesity is a difficult chronic condition to treat because of underlying metabolic dysfunction, chronic inflammation, cardiovascular effects, and its relapsing nature. GLP-1 RAs can interrupt the cycle of metabolic dysfunction and inflammation, improve multiple physiological systems, and reduce the risk of obesity-related chronic diseases, offering a more comprehensive approach to obesity than weight loss alone.³

Cardiorenal Outcomes

There is growing interest in the potential cardiorenal benefits of GLP-1 RAs, particularly among people with type 2 diabetes, obesity, chronic kidney disease, or elevated cardiometabolic risk. Several cardiovascular outcomes trials have reported reductions in major adverse cardiovascular events (MACE) with specific agents, including liraglutide, semaglutide, dulaglutide, albiglutide (since withdrawn from the market), and efpeglenatide (an investigational agent not approved by the FDA).^4-8 However, the magnitude and consistency of benefit have varied across products and study populations.

In people with overweight or obesity but without diabetes, the SELECT trial found that once-weekly semaglutide reduced the risk of MACE in participants with established cardiovascular disease.⁹ Renal outcomes are also of increasing interest. Earlier trials reported potential benefits on albuminuria and other kidney-related outcomes, and the dedicated FLOW trial found that semaglutide reduced the risk of a composite kidney outcome in people with type 2 diabetes and chronic kidney disease.¹⁰

Nevertheless, these findings should not automatically be generalized to all GLP-1–based therapies or populations. Claims about cardiovascular or renal protection should be tied to the specific product, patient population, end point definition, and trial data supporting them.

Prescribing Considerations

The popularity of GLP-1 RAs for obesity and type 2 diabetes has grown among both patients and health care providers. Providers are concerned about whether patients can balance appropriate use against potential risks, including extreme dietary restriction and excessive weight loss.

One key consideration is preventing over-suppression of appetite and its complications while maintaining a healthy weight and adequate diabetes control.¹¹ Recommendations before prescribing include screening for disordered eating behaviors, monitoring for adverse appetite-related responses, and prescribing cautiously in psychiatric populations.¹¹ Because GLP-1 RAs delay gastric emptying, they may alter the pharmacokinetics of some psychiatric medications, affecting their effectiveness or safety.¹¹

Cost and Coverage

Cost plays a major role in prescribing and affordability. More than adverse effects or age, medication cost is among the clearest predictors of whether a patient feels positive about their treatment.¹² Millions of commercially insured people in the United States lack coverage for GLP-1 RAs approved for weight loss, and even with coverage, restrictions such as prior authorization and step therapy add to patient dissatisfaction and out-of-pocket costs.¹²

List prices for brand-name agents remain above $1,000 per month, but cash-pay options have expanded. Manufacturer direct-to-consumer programs now offer Wegovy (semaglutide; Novo Nordisk) for $349 per month and Zepbound (tirzepatide; Eli Lilly) for $299 to $449 per month depending on dose, with similar prices listed on the federal TrumpRx platform.¹³ For many low-income patients, these out-of-pocket costs remain out of reach.

For Medicare and Medicaid beneficiaries, CMS introduced the BALANCE (Better Approaches to Lifestyle and Nutrition for Comprehensive hEalth) Model, under which CMS negotiates lower GLP-1 prices with manufacturers on behalf of participating state Medicaid programs and Medicare Part D plans.^14,15 The Medicaid component opened in May 2026, with states able to begin participating between May 1, 2026, and January 1, 2027.¹⁶

In April 2026, CMS announced that BALANCE would not launch in Medicare Part D in 2027 as originally planned.¹⁵ Instead, the Medicare GLP-1 Bridge, a separate demonstration that began July 1, 2026, and covers select GLP-1s for obesity outside the Part D benefit, was extended through December 31, 2027.^15,16

Coverage outside these programs remains limited. Medicaid coverage of GLP-1 RAs for obesity is optional for states, and as of January 2026, only 13 state Medicaid programs covered them for obesity treatment under fee-for-service, down from 16 in October 2025.¹⁷ Additional states have since considered dropping coverage because of budget pressures.¹⁸

The combination of high obesity prevalence, low wages, and restricted insurance coverage creates "GLP-1 deserts," where patients are left without access to these medications.¹⁹ This divides patients who can afford and benefit from GLP-1 RAs from those who cannot, and patients facing access barriers achieve less glycemic and weight control than those with uninterrupted access.

Pharmacists are often the ones who untangle these barriers. They can help patients navigate insurance requirements, complete prior authorizations, and connect with manufacturer and patient assistance programs.²⁰

Looking Ahead

In the United States, GLP-1–based therapies have become blockbuster treatments for type 2 diabetes and obesity, and their approved indications have expanded to include cardiovascular risk reduction, obstructive sleep apnea, and metabolic dysfunction-associated steatohepatitis (MASH).^17,21 Research is ongoing in other chronic conditions, including heart failure and substance use disorders.²²

Despite this momentum, high costs, insurance restrictions, and prior authorization requirements continue to keep many eligible patients from starting or staying on therapy.²² Beyond access support, pharmacists can coordinate clinic-based samples when available, provide education and monitoring, and adjust insulin regimens to promote safe, stable glycemic control.²⁰

GLP-1–based therapies may help shift obesity care toward a long-term, chronic disease management model. Their broader impact will depend on equitable access, sustainable affordability, continued evaluation of long-term safety and effectiveness, and integration with nutrition, physical activity, behavioral support, and multidisciplinary care.

References

1. Cleveland Clinic. GLP-1 agonists. Accessed September 28, 2026. https://my.clevelandclinic.org/health/treatments/13901-glp-1-agonists

2. Weight Loss Provider Guide. History of GLP-1 drugs. Accessed September 28, 2026. https://weightlossproviderguide.com/history-of-glp-1-drugs

3. iWhole Health. GLP-1s: more than weight loss—the missing link in chronic disease. Accessed September 28, 2026. https://www.iwholehealth.com/blog/glp-1s-more-than-weight-loss-the-missing-link-in-chronic-disease/

4. Marso SP, Daniels GH, Brown-Frandsen K, et al. Liraglutide and cardiovascular outcomes in type 2 diabetes. N Engl J Med. 2016;375(4):311-322. doi:10.1056/NEJMoa1603827

5. Marso SP, Bain SC, Consoli A, et al. Semaglutide and cardiovascular outcomes in patients with type 2 diabetes. N Engl J Med. 2016;375(19):1834-1844. doi:10.1056/NEJMoa1607141

6. Gerstein HC, Colhoun HM, Dagenais GR, et al. Dulaglutide and cardiovascular outcomes in type 2 diabetes (REWIND): a double-blind, randomised placebo-controlled trial. Lancet. 2019;394(10193):121-130. doi:10.1016/S0140-6736(19)31149-3

7. Hernandez AF, Green JB, Janmohamed S, et al. Albiglutide and cardiovascular outcomes in patients with type 2 diabetes and cardiovascular disease (HARMONY Outcomes): a multicentre, randomised, double-blind, placebo-controlled trial. Lancet. 2018;392(10157):1519-1529. doi:10.1016/S0140-6736(18)32261-X

8. Gerstein HC, Sattar N, Rosenstock J, et al. Cardiovascular and renal outcomes with efpeglenatide in type 2 diabetes. N Engl J Med. 2021;385(10):896-907. doi:10.1056/NEJMoa2108269

9. Lincoff AM, Brown-Frandsen K, Colhoun HM, et al. Semaglutide and cardiovascular outcomes in obesity without diabetes. N Engl J Med. 2023;389(24):2221-2232. doi:10.1056/NEJMoa2307563

10. Perkovic V, Tuttle KR, Rossing P, et al. Effects of semaglutide on chronic kidney disease in patients with type 2 diabetes. N Engl J Med. 2024;391(2):109-121. doi:10.1056/NEJMoa2403347

11. Richards JR, Khalsa SS. Highway to the danger zone? A cautionary account that GLP-1 receptor agonists may be too effective for unmonitored weight loss. Obes Rev. 2024;25(5):e13709. doi:10.1111/obr.13709

12. Marsh T. The state of GLP-1 patient experience: cost, access, satisfaction. GoodRx. May 6, 2026. Accessed September 21, 2026. https://www.goodrx.com/healthcare-access/research/glp1-medications-cost-access-patient-experience

13. Wingrove P. Novo Nordisk rolls out $349 Wegovy cash price ahead of plan. Reuters. November 17, 2025. Accessed November 6, 2026. https://www.ctvnews.ca/business/article/novo-nordisk-rolls-out-349-wegovy-cash-price-ahead-of-plan/

14. Centers for Medicare & Medicaid Services. Innovation insight: affordability of GLP-1s takes next step with BALANCE Model RFAs. 2026. Accessed September 21, 2026. https://www.cms.gov/priorities/innovation/innovation-insight-affordability-glp-1s-takes-next-step-balance-model-rfas

15. KFF. What to know about the BALANCE Model for GLP-1s in Medicare and Medicaid and the Medicare GLP-1 Bridge. Updated May 11, 2026. Accessed November 6, 2026. https://www.kff.org/medicare/issue-brief/what-to-know-about-the-balance-model-for-glp-1s-in-medicare-and-medicaid/

16. Academy of Managed Care Pharmacy. Regulatory NewsBREAK: CMS issues status update on the BRIDGE demo and BALANCE Model in Part D for CY 2027. April 2026. Accessed November 6, 2026. https://www.amcp.org/node/42137

17. KFF. Medicaid coverage of and spending on GLP-1s. January 16, 2026. Accessed November 6, 2026. https://www.kff.org/medicaid/issue-brief/medicaid-coverage-of-and-spending-on-glp-1s/

18. Stateline. More states consider dropping GLP-1 weight loss drugs from Medicaid. April 30, 2026. Accessed November 6, 2026. https://stateline.org/2026/04/30/more-states-consider-dropping-glp-1-weight-loss-drugs-from-medicaid/

19. HM Academy. The GLP-1 access gap: who can afford America's weight-loss drugs. 2025. Accessed September 21, 2026. https://hmacademy.com/blog/glp1-access-gap-affordability-by-state

20. Cochran A, Schalliol L, Lowe H, Owen S, Rosellini GV. Clinical impact of GLP-1 and GIP/GLP-1 agonist access barriers in primary care. JAPhA Pract Innov. Published online November 2025:100081. doi:10.1016/j.japhpi.2025.100081

21. US Food and Drug Administration. FDA approves treatment for serious liver disease known as "MASH." August 15, 2025. Accessed November 6, 2026. https://www.fda.gov/drugs/news-events-human-drugs/fda-approves-treatment-serious-liver-disease-known-mash

22. Sweet J. What's next for GLP-1s? Harvard Gazette. February 18, 2026. Accessed September 21, 2026. https://news.harvard.edu/gazette/story/2026/02/whats-next-for-glp-1s/