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Partial Needs Assessment*

Cardiovascular Care Among Obese Patients in a GLP-1 Receptor Agonist Landscape:

The Role of GLP-1 Receptor Agonists Beyond Diabetes

Written by Laura J. Arul, MD

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Executive Summary

The World Health Organization (WHO) describes obesity as a body mass index (BMI) greater than 30 and overweight as a BMI above 25.1About 42% of American adults are obese, according to recent statistics from the American Heart Association.2 In 2016, 650 million adults were obese worldwide, estimated to increase to 1 billion persons by 2030.3  The leading cause of death internationally is cardiovascular disease (CVD).4 Both obesity and CVD are highly prevalent, often comorbid, diseases with considerable public health consequences.

It is well-established that obesity is a risk factor for many conditions, including diabetes, hypertension, CVD, kidney disease, respiratory disease, and several types of cancer.1 Traditionally-recognized CVD risk factors include hypertension, diabetes, and dyslipidemia.5 Emerging evidence suggests that obesity may play a more direct role in the development of CVD rather than simply leading to the development of traditional risk factors resulting in CVD.5–7  This highlights the need to address obesity as part of the treatment of CVD.

In the past, treatment of obesity was limited to lifestyle interventions. Over the years, various pharmacotherapies, such as lorcaserin and orlistat,8 have been introduced. However, these older therapies have either been found to be unsafe or have resulted in intolerable side effects, limiting their utility. 8 Current treatment also includes naltrexone-bupropion. Crucially, none of these therapies have demonstrated a reduction in cardiovascular events.8 Bariatric surgery has also been a treatment option, but it is typically reserved for class II comorbid obesity or class III obesity and carries various surgical complications, thereby not making it a universally accessible or suitable option for all obese patients.8

In recent years, the introduction of glucagon-like peptide 1 receptor agonists (GLP-1 RAs), such as semaglutide, liraglutide, exenatide, tirzepatide, and dulaglutide, has revolutionized the treatment of obesity and type 2 diabetes (T2DM). The cardiovascular outcome trials (CVOTs) looked at the effect of GLP-1 RAs on the cardiovascular (CV) system in T2DM patients. GLP-1 RAs as a class have been observed to lower systolic blood pressure, reduce low-density lipoprotein (LDL), lower hemoglobin A1c (HbA1c) and lead to weight loss. 9 The AMPLITUDE-O, REWIND, Harmony Outcomes, SUSTAIN-6, and LEADER trials demonstrated the superiority of GLP-1 RAs over placebo in major adverse cardiovascular events (MACE, defined as CV death, nonfatal myocardial infarction (MI), and nonfatal stroke) reduction for patients with T2DM. 8

Most recently, new studies have shown the CV benefit of GLP-1 RAs in obese patients without diabetes. The SELECT trial showed that among patients with a BMI of 27 or higher and pre-existing CVD but no T2DM, treatment with semaglutide 2.4 mg once weekly reduced the risk of a composite of death from CV causes, nonfatal stroke, or nonfatal MI by 20%. 6 Also, from the SELECT trial data, semaglutide provided CV benefit in the overweight or obese regardless of baseline HbA1c and resulted in a 40% reduction in C-reactive protein (CRP) in the semaglutide group. 10 Additionally, semaglutide has demonstrated benefit in the HF population by reducing MACE, CV death, and hospitalization or urgent care visits for heart failure (HF). 11

Despite the proven cardiovascular benefit of GLP-1 RAs in obese patients with and without T2DM, prescription rates remain suboptimal. 12,13 Barriers to therapy include high treatment costs 14,15 and clinicians’ perception of obesity as a lifestyle choice rather than a disease,16 which may contribute to undertreatment. 8,16 This is reflected in cardiologists writing only 0.4% of GLP-1 RA prescriptions in the US in 2020.8 Obesity alone can increase the risk of adverse CV effects,6 which clinicians may not be aware of. Results from the ACTION study suggest there is an unfulfilled opportunity to teach clinicians about the pathophysiology of obesity.17 Recent evidence from SELECT and STEP-HFpEF trials and the CVOTs demonstrates significant CV benefits in T2DM and obese nondiabetics with CVD. 6,7,9 The low uptake of GLP-1 RA therapy could be due to a lack of awareness of the CV benefits of GLP-1 RAs or the view that this class of drugs is only for people with diabetes.12 Additional challenges include clinician uncertainty about initiating and managing GLP-1 RA treatment.13 Finally, obesity is often comorbid with T2DM.18 Therefore, when seeing patients with obesity and CVD, a clinician must have comfort in also understanding how to implement GLP-1 RA therapy into an existing diabetes regimen. This experience may be lacking among clinicians who treat CVD.12,13

Learning Objectives

After engaging in this learning activity, participants will be able to:

  1. Describe the dysfunctional effects caused by excess adipose tissue on various body systems that can result in the development of CVD.
  2. Discuss the effects of GLP-1 RAs on the CV system and summarize the evidence for CV benefit from GLP-1 RAs in T2DM and obese nondiabetic patients.   
  3. Design care plans that identify the most appropriate treatment according to individual patient needs for those with CVD and obesity, with and without T2DM, while anticipating real-world challenges to their implementation.

Identified Gaps

Knowledge GapsEducational NeedsLearning ObjectivesExpected Outcomes
Clinicians may be unaware of obesity’s role in CVD pathophysiology beyond contributing to traditional CVD risk factors of hypertension, diabetes and dyslipidemia.Clinicians need to understand how excess adipose tissue can have direct effects on the CV system, thereby recognizing the importance of addressing obesity in a CVD treatment plan. Describe the dysfunctional effects caused by excess adipose tissue on various body systems that can result in the development of CVD. Improved Knowledge (Level 3):Clinicians will understand how excess adipose tissue can have direct effects on the CV system, thereby recognizing the importance of addressing obesity in a CVD treatment plan.
GLP-1 RAs are a relatively new class of drugs, with research emerging on new indications for their use; clinicians may be unaware of the CV benefits that GLP-1 RAs provide in T2DM patients and obese nondiabetics.   Clinicians require education on how GLP-1 RAs work on the CV system, and their CV benefits in T2DM and obese nondiabetic patients.   Discuss the effects of GLP-1 RAs on the CV system and summarize the evidence for CV benefit from GLP-1 RAs in T2DM and obese nondiabetic patients.     Improved Knowledge (Level 3):Clinicians will have knowledge of the effects of GLP-1 RAs on the CV system, and summarize the evidence for CV benefit from GLP-1 RAs in T2DM and obese nondiabetic patients.     
Clinicians may be uncomfortable initiating GLP-1 RAs and counseling patients on their use, as well as how to modify a diabetic regimen, when adding GLP-1 RAs to a CVD treatment plan.Clinicians need knowledge and case examples of best-practice care plans that identify the most appropriate treatment in the setting of CVD and obesity, with or without T2DM, while anticipating real-world challenges to their implementation.Design care plans that identify the most appropriate treatment according to individual patient needs for those with CVD and obesity, with and without T2DM, while anticipating real-world challenges to their implementation. Improved knowledge, and competence (Level 3-4):Clinicians will be able to design care plans that identify the most appropriate treatment according to the needs of each patient with CVD and obesity, with and without T2DM, while anticipating real-world challenges to their implementation.

Summary

Both obesity and CVD represent significant public health challenges. While obesity has traditionally been viewed as a CVD risk factor through its contribution to conditions like hypertension and diabetes, emerging evidence suggests it may play a more direct role in CVD development. The introduction of GLP-1 RAs has shown benefits beyond glucose control and weight loss, with recent trials demonstrating significant CV benefit in diabetic and nondiabetic obese patients. However, several knowledge gaps limit the optimal implementation of this therapy: many clinicians may not fully understand obesity’s direct role in CVD pathophysiology, may be unaware of GLP-1 RAs’ CV benefits, and may lack confidence in managing GLP-1 RA therapy. This educational program addresses these gaps through expert-led sessions combining pathophysiology education, evidence review, and case-based learning.

References:

  1. Welsh A, Hammad M, Piña IL, Kulinski J. Obesity and cardiovascular health. Eur J Prev Cardiol. 2024;31(8):1026-1035. doi:10.1093/eurjpc/zwae025
  2. Tsao CW, Aday AW, Almarzooq ZI, et al. Heart Disease and Stroke Statistics—2023 Update: A Report From the American Heart Association. Circulation. 2023;147(8). doi:10.1161/CIR.0000000000001123
  3. Gallo G, Desideri G, Savoia C. Update on Obesity and Cardiovascular Risk: From Pathophysiology to Clinical Management. Nutrients. 2024;16(16). doi:10.3390/nu16162781
  4. Ryan DH, Lingvay I, Colhoun HM, et al. Semaglutide Effects on Cardiovascular Outcomes in People With Overweight or Obesity (SELECT) rationale and design. Am Heart J. 2020;229:61-69. doi:10.1016/j.ahj.2020.07.008
  5. Ndumele CE, Matsushita K, Lazo M, et al. Obesity and Subtypes of Incident Cardiovascular Disease. J Am Heart Assoc. 2016;5(8). doi:10.1161/JAHA.116.003921
  6. Lincoff AM, Brown-Frandsen K, Colhoun HM, et al. Semaglutide and Cardiovascular Outcomes in Obesity without Diabetes. New England Journal of Medicine. 2023;389(24):2221-2232. doi:10.1056/nejmoa2307563
  7. Kosiborod MN, Abildstrøm SZ, Borlaug BA, et al. Semaglutide in Patients with Heart Failure with Preserved Ejection Fraction and Obesity. New England Journal of Medicine. 2023;389(12):1069-1084. doi:10.1056/nejmoa2306963
  8. Michos ED, Lopez-Jimenez F, Gulati M. Role of Glucagon-Like Peptide-1 Receptor Agonists in Achieving Weight Loss and Improving Cardiovascular Outcomes in People With Overweight and Obesity. J Am Heart Assoc. 2023;12(11). doi:10.1161/JAHA.122.029282
  9. Marx N, Husain M, Lehrke M, Verma infodh, Sattar N. GLP-1 Receptor Agonists for Reducing Atherosclerotic Cardiovascular Risk in Patients with Type 2 Diabetes. Circulation. 2022;146(24):1882-1894. doi:10.1161/CIRCULATIONAHA.122.059595
  10. Lingvay I, Deanfield J, Kahn SE, et al. Semaglutide and Cardiovascular Outcomes by Baseline HbA1c and Change in HbA1c in People With Overweight or Obesity Without Diabetes in SELECT. Diabetes Care. 2024;47(8):1360-1369. doi:10.2337/dc24-0764
  11. Deanfield J, Verma S, Scirica BM, et al. Semaglutide and cardiovascular outcomes in patients with obesity and prevalent heart failure: a prespecified analysis of the SELECT trial. The Lancet. 2024;404(10454):773-786. doi:10.1016/S0140-6736(24)01498-3
  12. King A, Tan X, Dhopeshwarkar N, et al. Recent trends in GLP-1 RA and SGLT2i use among people with type 2 diabetes and atherosclerotic cardiovascular disease in the USA. BMJ Open Diabetes Res Care. 2024;12(5). doi:10.1136/bmjdrc-2024-004431
  13. Honigberg MC, Chang LS, McGuire DK, Plutzky J, Aroda VR, Vaduganathan M. Use of Glucagon-Like Peptide-1 Receptor Agonists in Patients with Type 2 Diabetes and Cardiovascular Disease: A Review. JAMA Cardiol. 2020;5(10):1182-1190. doi:10.1001/jamacardio.2020.1966
  14. Kumar S, Blaha MJ. GLP-1 RA for cardiometabolic risk reduction in obesity – How do we best describe benefit and value? Am J Prev Cardiol. 2024;18. doi:10.1016/j.ajpc.2024.100682
  15. Zomer E, Zhou J, Nelson AJ, Nicholls SJ, Stub D, Zoungas S. Semaglutide for the Secondary Prevention of Cardiovascular Disease in People with Overweight or Obesity, but without Diabetes: A Cost-Effectiveness Analysis. https://academic.oup.com/eurheartj/article/45/Supplement_1/ehae666.3623/7839406
  16. Shahed Q, Baranowska K, Galavazi MC, Cao Y, Van Nieuwenhoven MA. Doctors and patients’ perspectives on obesity. A Q-methodology study. Fam Pract. 2022;39(4):694-700. doi:10.1093/fampra/cmab169
  17. Kaplan LM, Golden A, Jinnett K, et al. Perceptions of Barriers to Effective Obesity Care: Results from the National ACTION Study. Obesity. 2018;26(1):61-69. doi:10.1002/oby.22054
  18. Nianogo RA, Arah OA. Forecasting Obesity and Type 2 Diabetes Incidence and Burden: The ViLA-Obesity Simulation Model. Front Public Health. 2022;10. doi:10.3389/fpubh.2022.818816
  19. Ferhatbegović L, Mršić D, Macić-Džanković A. The benefits of GLP1 receptors in cardiovascular diseases. Frontiers in Clinical Diabetes and Healthcare. 2023;4. doi:10.3389/fcdhc.2023.1293926
  20. Yang CT, Yang CY, Ou HT, Kuo S. Comparative cardiovascular safety of GLP-1 receptor agonists versus other glucose-lowering agents in real-world patients with type 2 diabetes: A nationwide population-based cohort study. Cardiovasc Diabetol. 2020;19(1). doi:10.1186/s12933-020-01053-0
  21. Mellbin LG, Bhatt DL, David JP, et al. Semaglutide and cardiovascular outcomes by baseline HbA1c in diabetes: the SUSTAIN 6 and PIONEER 6 trials. Eur Heart J. 2024;45(15):1371-1374. doi:10.1093/eurheartj/ehae028
  22. Gov Id C, Lilly E. A Study of Tirzepatide (LY3298176) on Reducing Morbidity and Mortality in Adults With Obesity (SURMOUNT-MMO) Obesity Overweight. https://clinicaltrials.gov/study-basics/how-to-read-study-record#contacts-and-locations

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*The complete Needs Assessment Sample is available upon request.