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Peer-reviewedCC BY-NC 4.0Diabetes Therapy

Comparing Cardiovascular Outcomes in New Users of Oral Semaglutide Versus Other Noninsulin Glucose-Lowering Therapies Among Adults with Type 2 Diabetes and Atherosclerotic Cardiovascular Disease

  • Xi Tan1
  • Yuanjie Liang1
  • Caichen Zhong1
  • Lin Xie1
  • Mico Guevarra1
  • Caroline Swift1
  • Adam de Havenon2
  1. 1Novo Nordisk Inc, Plainsboro, NJ USA
  2. 2Department of Neurology, Center for Brain and Mind Health, Yale School of Medicine, Yale University, 15 York St, New Haven, CT 06510 USA
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Abstract

Introduction: Clinical trials have found semaglutide reduces the risk of major adverse cardiovascular events (MACE) among people with type 2 diabetes (T2D) at high risk of MACE. Less is known about oral semaglutide’s impact on real-world cardiovascular risk.

Methods: This observational cohort study used administrative claims data from Optum’s deidentified Clinformatics® Data Mart Database to compare 3-, modified 3-, 5-, modified 5-, and 2-point MACE, ischemic stroke (IS), myocardial infarction (MI), and all-cause and cardiovascular-related death rates among people with T2D and atherosclerotic cardiovascular disease (ASCVD) who initiated oral semaglutide vs other noninsulin glucose-lowering therapies (ONIGLTs). Cardiovascular outcomes were compared between new users of oral semaglutide and propensity score-matched new users of dipeptidyl peptidase 4 inhibitors (DPP4is) or sodium-glucose cotransporter 2 inhibitors (SGLT2is).

Results: Oral semaglutide users (n = 10,878) had risk reductions of 17% and 21% in 3- and modified 3-point MACE, respectively, and significant risk reductions in 5-, modified 5-, and 2-point MACE, IS, and all-cause death vs ONIGLT users (n = 28,639). People who initiated oral semaglutide (n = 7218) had 22% and 24% lower risks of 3- and modified 3-point MACE, respectively, and significantly lower risks of 5- and modified 5-point MACE, IS, and all-cause death vs people who initiated DPP4is (n = 7218). Compared with SGLT2i users (n = 21,572), oral semaglutide users (n = 7491) had 21% and 22% lower risks of 3- and modified 3-point MACE, respectively, and significantly lower risks of 5-, modified 5-, and 2-point MACE.

Conclusion: Consistent with clinical trial evidence, oral semaglutide was associated with a lower risk of cardiovascular outcomes among people with T2D and ASCVD in real-world settings.

Supplementary Information: The online version contains supplementary material available at https://doi.org/10.1007/s13300-026-01919-8.

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Cite

BibTeXRIS
BibTeX
@article{tan2026comparing,
  title = {{Comparing Cardiovascular Outcomes in New Users of Oral Semaglutide Versus Other Noninsulin Glucose-Lowering Therapies Among Adults with Type 2 Diabetes and Atherosclerotic Cardiovascular Disease}},
  author = {Xi Tan and Yuanjie Liang and Caichen Zhong and Lin Xie and Mico Guevarra and Caroline Swift and Adam de Havenon},
  journal = {Diabetes Therapy},
  year = {2026},
  month = sep,
  doi = {10.1007/s13300-026-01919-8},
  url = {https://doi.org/10.1007/s13300-026-01919-8},
  note = {CC BY-NC 4.0},
}
RIS
TY  - JOUR
TI  - Comparing Cardiovascular Outcomes in New Users of Oral Semaglutide Versus Other Noninsulin Glucose-Lowering Therapies Among Adults with Type 2 Diabetes and Atherosclerotic Cardiovascular Disease
AU  - Xi Tan
AU  - Yuanjie Liang
AU  - Caichen Zhong
AU  - Lin Xie
AU  - Mico Guevarra
AU  - Caroline Swift
AU  - Adam de Havenon
PY  - 2026
DA  - 2026/09/17
JO  - Diabetes Therapy
DO  - 10.1007/s13300-026-01919-8
UR  - https://doi.org/10.1007/s13300-026-01919-8
AB  - Introduction: Clinical trials have found semaglutide reduces the risk of major adverse cardiovascular events (MACE) among people with type 2 diabetes (T2D) at high risk of MACE. Less is known about oral semaglutide’s impact on real-world cardiovascular risk.  Methods: This observational cohort study used administrative claims data from Optum’s deidentified Clinformatics® Data Mart Database to compare 3-, modified 3-, 5-, modified 5-, and 2-point MACE, ischemic stroke (IS), myocardial infarction (MI), and all-cause and cardiovascular-related death rates among people with T2D and atherosclerotic cardiovascular disease (ASCVD) who initiated oral semaglutide vs other noninsulin glucose-lowering therapies (ONIGLTs). Cardiovascular outcomes were compared between new users of oral semaglutide and propensity score-matched new users of dipeptidyl peptidase 4 inhibitors (DPP4is) or sodium-glucose cotransporter 2 inhibitors (SGLT2is).  Results: Oral semaglutide users (n = 10,878) had risk reductions of 17% and 21% in 3- and modified 3-point MACE, respectively, and significant risk reductions in 5-, modified 5-, and 2-point MACE, IS, and all-cause death vs ONIGLT users (n = 28,639). People who initiated oral semaglutide (n = 7218) had 22% and 24% lower risks of 3- and modified 3-point MACE, respectively, and significantly lower risks of 5- and modified 5-point MACE, IS, and all-cause death vs people who initiated DPP4is (n = 7218). Compared with SGLT2i users (n = 21,572), oral semaglutide users (n = 7491) had 21% and 22% lower risks of 3- and modified 3-point MACE, respectively, and significantly lower risks of 5-, modified 5-, and 2-point MACE.  Conclusion: Consistent with clinical trial evidence, oral semaglutide was associated with a lower risk of cardiovascular outcomes among people with T2D and ASCVD in real-world settings.  Supplementary Information: The online version contains supplementary material available at https://doi.org/10.1007/s13300-026-01919-8.
SN  - 1869-6953
SN  - 1869-6961
ER  -