Comparative effectiveness of OW GLP-1 RAs and other glucose-lowering therapies among Medicare beneficiaries with T2D and ASCVD

Diabetes Res Clin Pract. 2025 Nov:229:112473. doi: 10.1016/j.diabres.2025.112473. Epub 2025 Sep 9.

Abstract

Aims: To compare the incidence rates for cardiovascular (CV) outcomes and healthcare resource utilization (HCRU) and costs among patients treated with once-weekly (OW) glucagon-like peptide-1 receptor agonists (GLP-1 RAs) compared with other non-insulin glucose lowering therapies (ONIGLTs).

Methods: This was an observational cohort study using Medicare fee-for-service claims data (2006-2022). Medicare beneficiaries with T2D and ASCVD treated with OW GLP-1 RAs or ONIGLTs were matched using propensity score matching.

Results: Among the total 398,470 Medicare beneficiaries, OW GLP-1 RAs were associated with reduced risk of CV events (hazard ratios [HRs] range: 0.72 to 0.88, P < 0.05 for all) compared with ONIGLTs, in addition to lower HCRU and costs including ASCVD-related total medical visits (incidence rate ratio [95 % CI]: 0.91 [0.90-0.93]; P < 0.001) and total medical costs (mean cost ratio [95 %CI]: 0.88 [0.86-0.91]; P < 0.001). Among OW GLP-1 RAs, semaglutide had the lowest risk of all CV outcomes when compared with SGLT2is (HRs range: 0.80 to 0.85, P < 0.05 for all) and DPP-4is (HRs range: 0.58 to 0.73; P < 0.001 for all).

Conclusion: The study findings corroborate current guideline recommendations for GLP-1 RAs in people with T2D and ASCVD, and extend findings to lower HCRU and costs in a real-world setting, most notably for semaglutide.

Keywords: Atherosclerotic cardiovascular disease; Glucagon-like peptide-1 receptor agonists; Healthcare cost; Major adverse cardiovascular events; Semaglutide; Type 2 diabetes.

Publication types

  • Observational Study
  • Comparative Study

MeSH terms

  • Aged
  • Aged, 80 and over
  • Cardiovascular Diseases* / epidemiology
  • Cardiovascular Diseases* / prevention & control
  • Diabetes Mellitus, Type 2* / complications
  • Diabetes Mellitus, Type 2* / drug therapy
  • Diabetes Mellitus, Type 2* / economics
  • Diabetes Mellitus, Type 2* / epidemiology
  • Female
  • Glucagon-Like Peptide-1 Receptor Agonists*
  • Humans
  • Hypoglycemic Agents* / administration & dosage
  • Hypoglycemic Agents* / economics
  • Hypoglycemic Agents* / therapeutic use
  • Male
  • Medicare / statistics & numerical data
  • United States / epidemiology

Substances

  • Hypoglycemic Agents
  • Glucagon-Like Peptide-1 Receptor Agonists