Weekly GLP-1s Significantly Reduce Cardiovascular Risks

Once-weekly (OW) glucagon-like peptide-1 receptor agonists (GLP-1 RAs) were associated with a significant decrease in cardiovascular (CV) risk compared with other noninsulin glucose-lowering therapies (ONIGLTs). Furthermore, OW GLP-1 RAs were also associated with a decreased out-of-pocket burden when compared with patients prescribed ONIGLTs, according to a study in Diabetes Research and Clinical Practice.¹ 

“In people with type 2 diabetes (T2D), atherosclerotic cardiovascular disease (ASCVD) is associated with significantly increased morbidity, mortality, and health care resource utilization (HCRU),” wrote the authors of the study. “Guidelines recommend the initiation of sodium-glucose cotransporter-2 inhibitors (SGLT2is) or GLP-1 RAs in individuals with T2D and ASCVD, or at high risk for ASCVD.”

Blockbuster drug names like Ozempic and Wegovy—both branded formulations of semaglutide—have now become common in today’s health care discussions thanks to their weight-loss benefits. Ozempic use increased 40-fold from 2019 to 2022, while other semaglutide formulas and weight-loss drugs continue to take up space in the drug market. However, according to the same study, GLP-1 use was still greater in populations prescribed them for T2D and CV conditions.²

While OW GLP-1s have been approved since 2012, there is little evidence comparing their costs and HCRU among patients in the real world. | image credit: SHUMAYA / stock.adobe.com

READ MORE: Hypertension Mortality Rose Significantly from 1999 to 2019

Whether patients are seeking this specific drug class for weight loss or to treat cardiometabolic conditions, their access and costs have been a significant topic of discussion within the health care sector amid the sheer growth in GLP-1 use during recent years. Despite GLP-1s being staples of diabetes and CV care—and now obesity treatment—experts are still struggling to deem this drug class cost-effective due to a $700-$800 monthly threshold.³

Amid constant cost concerns and increased evidence of these drugs’ unprecedented impacts, researchers have been working hard in the drug development space to make GLP-1s more useful, cost-effective, and accessible for the patients that need them. Although OW GLP-1s have been approved since 2012, there is little evidence comparing their costs and HCRU among patients in the real world who are actually in need of these drugs.^1,4

“The new generation of OW GLP-1 RAs, which include extended-release (ER) exenatide (Bydureon), dulaglutide (Trulicity), semaglutide (Ozempic), and the dual glucose-dependent insulinotropic polypeptide (GIP) and GLP-1 RA tirzepatide (Mounjaro), are associated with increased adherence over older generations of GLP-1 RAs and now account for the majority of GLP-1 RA prescriptions in the US,” the authors continued.¹ “This study aimed to compare CV outcomes, HCRU, and costs among Medicare beneficiaries with T2D and ASCVD initiating a new treatment with OW GLP-1 RAs or ONIGLTs.”

In their observational cohort study, researchers used Medicare fee-for-service (FFS) claims data between 2006 and 2022. The analysis included Medicare beneficiaries reporting T2D and ASCVD that were prescribed either OW GLP-1 RAs or ONIGLTs. Furthermore, based on the study’s focus toward a population of Medicare beneficiaries, participants included in the analysis were all above the age of 65 years old.

To observe the primary study outcomes, researchers placed participants into separate GLP-1 RA and ONIGLT treatment arms to compare each group’s association with CV incidence rates and HCRU through various medical visits. They also explored the costs of HCRU and adjusted them to reflect 2022 US dollars.

The final analysis included 77,712 patients (mean age, 73.7 years; 88.8% white) using GLP-1 RAs and 174,620 prescribed ONIGLT treatment (mean age, 73.7 years; 87.2% White). “In the US FFS Medicare population with T2D and ASCVD, treatment with OW GLP-1 RAs was associated with decreased CV risks and lower HCRU and costs compared [with] ONIGLTs.”

Across the board, GLP-1 RA treatment was more effective than ONIGLTs such as SGLT2is and dipeptidyl peptidase-4 inhibitors (DPP-4is).

First, GLP-1s outperformed their matched cohort of patients on ONIGLTs by more significantly lowering risks of ischemic stroke, myocardial infarction, and 2-point, 3-point, and 5-point major adverse cardiovascular events (MACE). The main cost-benefit occurrence uncovered in this study was how ASCVD-related medical visits were significantly lower for the GLP-1 RA cohort than the ONIGLT group.

With researchers’ current understanding of OW GLP-1s growing in real time, the opportunities for patients to access this drug class for CV complications and T2D may also be growing at a similar pace. Despite debates surrounding this access, as well as the massive GLP-1 expenditures that have been reported,⁵ finding optimal levels of cost-effectiveness and risk-reduction among these drugs will benefit patients in the future.

“Compared with ONIGLTs, OW GLP-1 RAs were associated with significantly reduced risk of CV outcomes in the US Medicare population,” concluded the authors.¹ “The findings further support guideline-recommended use of OW GLP-1 RAs for people with T2D and ASCVD and provide additional evidence to guide treatment decisions in this population.”

READ MORE: Diabetes Resource Center

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REFERENCES

1. Tan X, Harton J, Gutierrez C, et al. Comparative effectiveness of OW GLP-1 RAs and other glucose-lowering therapies among Medicare beneficiaries with T2D and ASCVD. Diabetes Res Clin Pract. 2025;229:112473. https://doi.org/10.1016/j.diabres.2025.112473

2. Watanabe JH, Kwon J, Nan B, et al. Trends in glucagon-like peptide 1 receptor agonist use, 2014 to 2022. JAPhA. 2023;64(1):133-138. https://doi.org/10.1016/j.japh.2023.10.002

3. Niewijk G. Are GLP-1 drugs worth their current cost? The University of Chicago Medicine. June 16, 2025. Accessed September 17, 2025. https://www.uchicagomedicine.org/forefront/research-and-discoveries-articles/glp-1-drug-pricing-analysis

4. Evolution of GLP-1 receptor agonists for diabetes treatment. Biopharma PEG Scientific Inc. September 22, 2022. Accessed September 17, 2025. https://www.biochempeg.com/article/299.html

5. O’Reilly KB. Spending on GLP-1s has grown dramatically. Here are the details. American Medical Association. August 27, 2025. Accessed September 17, 2025. https://www.ama-assn.org/public-health/prevention-wellness/spending-glp-1s-has-grown-dramatically-here-are-details