Comparative cardiovascular outcomes and safety of hypoglycemic drug classes in patients with type 2 diabetes and hypertension: a multicenter cohort analysis

Abstract Background Patients with type 2 diabetes (T2D) and hypertension are at increased risk of adverse cardiovascular (CV) events. However, real-world evidence comparing the CV effectiveness and safety of major hypoglycemic drug classes remains limited in this population. This multicenter pooled...

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Main Authors: Zhiyuan Wei, Wanqian Xu, Yu Wang, Yu Tian, Zhongmin Wang, Shenqi Jing, Weina Liu, Sipeng Shen, Chenlong Qin, Xin Zhang, Jingsong Li, Yun Liu
Format: Article
Language:English
Published: BMC 2025-08-01
Series:Cardiovascular Diabetology
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Online Access:https://doi.org/10.1186/s12933-025-02892-5
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author Zhiyuan Wei
Wanqian Xu
Yu Wang
Yu Tian
Zhongmin Wang
Shenqi Jing
Weina Liu
Sipeng Shen
Chenlong Qin
Xin Zhang
Jingsong Li
Yun Liu
author_facet Zhiyuan Wei
Wanqian Xu
Yu Wang
Yu Tian
Zhongmin Wang
Shenqi Jing
Weina Liu
Sipeng Shen
Chenlong Qin
Xin Zhang
Jingsong Li
Yun Liu
author_sort Zhiyuan Wei
collection DOAJ
description Abstract Background Patients with type 2 diabetes (T2D) and hypertension are at increased risk of adverse cardiovascular (CV) events. However, real-world evidence comparing the CV effectiveness and safety of major hypoglycemic drug classes remains limited in this population. This multicenter pooled analysis aims to directly compare the CV outcomes and safety profiles of these key agents in patients with T2D and hypertension. Methods We analyzed electronic health records from two databases in a cohort study of T2D patients with hypertension who had initiated metformin as first-line therapy. Propensity score matching (PSM) and Cox proportional hazards models were used to compare the risks of 3-/4-point major adverse cardiovascular events (MACE) and safety outcomes across drug classes added to metformin: insulin, sulfonylureas (SUs), glucagon-like peptide-1 receptor agonists (GLP-1 RAs), dipeptidyl peptidase-4 inhibitors (DPP4is), glinides, acarbose, and sodium-glucose transporter 2 inhibitors (SGLT2is). Results Compared with insulin, GLP-1 RAs, DPP4is, and glinides were associated with a lower risk of 3-point MACE (HR: 0.48 [0.31–0.76], 0.70 [0.57–0.85], and 0.70 [0.52–0.94], respectively). SUs were associated with a higher risk of 3-point MACE compared with DPP4is (HR: 1.30 [1.06–1.59]). DPP4is, GLP-1 RAs, and glinides showed a lower risk of 3-point MACE compared with acarbose (HR: 0.62 [0.51–0.76], 0.47 [0.29–0.75], and 0.59 [0.43–0.81], respectively). Similar patterns were observed for 4-point MACE. For safety outcomes, DPP4is were associated with a reduced risk of chronic kidney disease, while insulin use was associated with reduced risks of inflammatory polyarthritis and insomnia. However, DPP4is were associated with higher risks of coronary atherosclerotic diseases and hypertensive heart disease. Conclusions This study highlights the differential cardiovascular effectiveness and safety profiles of hypoglycemic therapies in real-world settings, providing valuable insights for optimizing T2D management, particularly in patients with comorbid hypertension.
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spelling doaj-art-4f73df1ad0f9404e9396a2ede0efd8ee2025-08-24T11:06:31ZengBMCCardiovascular Diabetology1475-28402025-08-0124111310.1186/s12933-025-02892-5Comparative cardiovascular outcomes and safety of hypoglycemic drug classes in patients with type 2 diabetes and hypertension: a multicenter cohort analysisZhiyuan Wei0Wanqian Xu1Yu Wang2Yu Tian3Zhongmin Wang4Shenqi Jing5Weina Liu6Sipeng Shen7Chenlong Qin8Xin Zhang9Jingsong Li10Yun Liu11Department of Medical Informatics, School of Biomedical Engineering and Informatics, Nanjing Medical UniversityGeneral Practice Medical Center, Chinese Evidence-Based Medicine Center, West China Hospital, Sichuan University Research Center for Scientific Data Hub , Zhejiang Lab Engineering Research Center of EMR and Intelligent Expert System, Ministry of Education, College of Biomedical Engineering and Instrument Science, Zhejiang University Department of Medical Informatics, School of Biomedical Engineering and Informatics, Nanjing Medical UniversityDepartment of Medical Informatics, School of Biomedical Engineering and Informatics, Nanjing Medical University Department of Nutrition and Food Hygiene, School of Public Health , Southeast University Department of Biostatistics, Center for Global Health, School of Public Health, Nanjing Medical UniversityDepartment of Medical Informatics, School of Biomedical Engineering and Informatics, Nanjing Medical UniversityDepartment of Medical Informatics, School of Biomedical Engineering and Informatics, Nanjing Medical University Research Center for Scientific Data Hub , Zhejiang Lab Department of Medical Informatics, School of Biomedical Engineering and Informatics, Nanjing Medical UniversityAbstract Background Patients with type 2 diabetes (T2D) and hypertension are at increased risk of adverse cardiovascular (CV) events. However, real-world evidence comparing the CV effectiveness and safety of major hypoglycemic drug classes remains limited in this population. This multicenter pooled analysis aims to directly compare the CV outcomes and safety profiles of these key agents in patients with T2D and hypertension. Methods We analyzed electronic health records from two databases in a cohort study of T2D patients with hypertension who had initiated metformin as first-line therapy. Propensity score matching (PSM) and Cox proportional hazards models were used to compare the risks of 3-/4-point major adverse cardiovascular events (MACE) and safety outcomes across drug classes added to metformin: insulin, sulfonylureas (SUs), glucagon-like peptide-1 receptor agonists (GLP-1 RAs), dipeptidyl peptidase-4 inhibitors (DPP4is), glinides, acarbose, and sodium-glucose transporter 2 inhibitors (SGLT2is). Results Compared with insulin, GLP-1 RAs, DPP4is, and glinides were associated with a lower risk of 3-point MACE (HR: 0.48 [0.31–0.76], 0.70 [0.57–0.85], and 0.70 [0.52–0.94], respectively). SUs were associated with a higher risk of 3-point MACE compared with DPP4is (HR: 1.30 [1.06–1.59]). DPP4is, GLP-1 RAs, and glinides showed a lower risk of 3-point MACE compared with acarbose (HR: 0.62 [0.51–0.76], 0.47 [0.29–0.75], and 0.59 [0.43–0.81], respectively). Similar patterns were observed for 4-point MACE. For safety outcomes, DPP4is were associated with a reduced risk of chronic kidney disease, while insulin use was associated with reduced risks of inflammatory polyarthritis and insomnia. However, DPP4is were associated with higher risks of coronary atherosclerotic diseases and hypertensive heart disease. Conclusions This study highlights the differential cardiovascular effectiveness and safety profiles of hypoglycemic therapies in real-world settings, providing valuable insights for optimizing T2D management, particularly in patients with comorbid hypertension.https://doi.org/10.1186/s12933-025-02892-5Type 2 diabetesHypertensionMajor adverse cardiovascular events (MACE)Cardiovascular safetyReal-world evidenceRetrospective study
spellingShingle Zhiyuan Wei
Wanqian Xu
Yu Wang
Yu Tian
Zhongmin Wang
Shenqi Jing
Weina Liu
Sipeng Shen
Chenlong Qin
Xin Zhang
Jingsong Li
Yun Liu
Comparative cardiovascular outcomes and safety of hypoglycemic drug classes in patients with type 2 diabetes and hypertension: a multicenter cohort analysis
Cardiovascular Diabetology
Type 2 diabetes
Hypertension
Major adverse cardiovascular events (MACE)
Cardiovascular safety
Real-world evidence
Retrospective study
title Comparative cardiovascular outcomes and safety of hypoglycemic drug classes in patients with type 2 diabetes and hypertension: a multicenter cohort analysis
title_full Comparative cardiovascular outcomes and safety of hypoglycemic drug classes in patients with type 2 diabetes and hypertension: a multicenter cohort analysis
title_fullStr Comparative cardiovascular outcomes and safety of hypoglycemic drug classes in patients with type 2 diabetes and hypertension: a multicenter cohort analysis
title_full_unstemmed Comparative cardiovascular outcomes and safety of hypoglycemic drug classes in patients with type 2 diabetes and hypertension: a multicenter cohort analysis
title_short Comparative cardiovascular outcomes and safety of hypoglycemic drug classes in patients with type 2 diabetes and hypertension: a multicenter cohort analysis
title_sort comparative cardiovascular outcomes and safety of hypoglycemic drug classes in patients with type 2 diabetes and hypertension a multicenter cohort analysis
topic Type 2 diabetes
Hypertension
Major adverse cardiovascular events (MACE)
Cardiovascular safety
Real-world evidence
Retrospective study
url https://doi.org/10.1186/s12933-025-02892-5
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