Glycemic levels and cardiovascular events in type 2 diabetes: A cohort study of drugs with different hypoglycemic potentials

Abstract Research indicates a U-shaped association between mortality and glycated hemoglobin (HbA1c) levels in patients receiving sulfonylurea or insulin. However, the relationship between glucose levels and cardiovascular events in patients on novel agents with a lower hypoglycemic potential remain...

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Main Authors: Yi-Cheng Lin, Chih-Wei Chen, Ling-Ya Huang, Bi-Li Chen, Yu-Hsuan Joni Shao, Chun-Yao Huang
Format: Article
Language:English
Published: Nature Portfolio 2025-08-01
Series:Scientific Reports
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Online Access:https://doi.org/10.1038/s41598-025-10215-7
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author Yi-Cheng Lin
Chih-Wei Chen
Ling-Ya Huang
Bi-Li Chen
Yu-Hsuan Joni Shao
Chun-Yao Huang
author_facet Yi-Cheng Lin
Chih-Wei Chen
Ling-Ya Huang
Bi-Li Chen
Yu-Hsuan Joni Shao
Chun-Yao Huang
author_sort Yi-Cheng Lin
collection DOAJ
description Abstract Research indicates a U-shaped association between mortality and glycated hemoglobin (HbA1c) levels in patients receiving sulfonylurea or insulin. However, the relationship between glucose levels and cardiovascular events in patients on novel agents with a lower hypoglycemic potential remains unknown. This study was aimed to examine the association between cardiovascular events and HbA1c in patients with type 2 diabetes receiving drugs with different hypoglycemic potentials. This is an observational cohort study using a multicenter electronic medical record database. This study included patients who received a diagnosis of type 2 diabetes between 2009 and 2020 and received non-insulin antidiabetic drugs. These drugs were divided into drugs with a high-hypoglycemic-risk (sulfonylurea and meglitinides) and drugs with a low-hypoglycemic-risk (incretin mimetics, sodium-glucose cotransporter-2 inhibitors, thiazolidinediones, and acarbose). The events of interest were mortality and major adverse cardiovascular events (MACEs). A total of 6,789 patients were included, with 3,191 patients in low-hypoglycemic-risk drugs cohort and 3,598 patients in high-hypoglycemic-risk drugs cohort. Both cohorts exhibited a U-shaped association between HbA1c levels and the risk of mortality and MACEs. Among patients receiving low-hypoglycemic-risk drugs, HbA1c levels of 6.7% and 6.8% were associated with the lowest risk of mortality and MACEs, respectively. Similarly, in patients receiving high-hypoglycemic-risk drugs, the lowest risk of mortality and MACEs was observed at HbA1c levels of 6.8% and 7.2%, respectively. Both low and high HbA1c levels were associated with an increased risk of mortality and cardiovascular events, whereas intermediate levels were linked to the lowest risk. These findings support a U-shaped association between glycemic control and adverse outcomes in patients with type 2 diabetes receiving non-insulin-based therapies.
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spelling doaj-art-e4b4edbebcca4188909e8a1fde8a826f2025-08-20T03:04:38ZengNature PortfolioScientific Reports2045-23222025-08-0115111010.1038/s41598-025-10215-7Glycemic levels and cardiovascular events in type 2 diabetes: A cohort study of drugs with different hypoglycemic potentialsYi-Cheng Lin0Chih-Wei Chen1Ling-Ya Huang2Bi-Li Chen3Yu-Hsuan Joni Shao4Chun-Yao Huang5Department of Pharmacy, Taipei Medical University HospitalDivision of Cardiology, Department of Internal Medicine, Taipei Medical University HospitalHealth Data Analytics and Statistics Center, Office of Data Science, Taipei Medical UniversityDepartment of Pharmacy, Taipei Medical University HospitalHealth Data Analytics and Statistics Center, Office of Data Science, Taipei Medical UniversityDivision of Cardiology, Department of Internal Medicine, Taipei Medical University HospitalAbstract Research indicates a U-shaped association between mortality and glycated hemoglobin (HbA1c) levels in patients receiving sulfonylurea or insulin. However, the relationship between glucose levels and cardiovascular events in patients on novel agents with a lower hypoglycemic potential remains unknown. This study was aimed to examine the association between cardiovascular events and HbA1c in patients with type 2 diabetes receiving drugs with different hypoglycemic potentials. This is an observational cohort study using a multicenter electronic medical record database. This study included patients who received a diagnosis of type 2 diabetes between 2009 and 2020 and received non-insulin antidiabetic drugs. These drugs were divided into drugs with a high-hypoglycemic-risk (sulfonylurea and meglitinides) and drugs with a low-hypoglycemic-risk (incretin mimetics, sodium-glucose cotransporter-2 inhibitors, thiazolidinediones, and acarbose). The events of interest were mortality and major adverse cardiovascular events (MACEs). A total of 6,789 patients were included, with 3,191 patients in low-hypoglycemic-risk drugs cohort and 3,598 patients in high-hypoglycemic-risk drugs cohort. Both cohorts exhibited a U-shaped association between HbA1c levels and the risk of mortality and MACEs. Among patients receiving low-hypoglycemic-risk drugs, HbA1c levels of 6.7% and 6.8% were associated with the lowest risk of mortality and MACEs, respectively. Similarly, in patients receiving high-hypoglycemic-risk drugs, the lowest risk of mortality and MACEs was observed at HbA1c levels of 6.8% and 7.2%, respectively. Both low and high HbA1c levels were associated with an increased risk of mortality and cardiovascular events, whereas intermediate levels were linked to the lowest risk. These findings support a U-shaped association between glycemic control and adverse outcomes in patients with type 2 diabetes receiving non-insulin-based therapies.https://doi.org/10.1038/s41598-025-10215-7DiabetesHbA1cMortalityMajor adverse cardiovascular events
spellingShingle Yi-Cheng Lin
Chih-Wei Chen
Ling-Ya Huang
Bi-Li Chen
Yu-Hsuan Joni Shao
Chun-Yao Huang
Glycemic levels and cardiovascular events in type 2 diabetes: A cohort study of drugs with different hypoglycemic potentials
Scientific Reports
Diabetes
HbA1c
Mortality
Major adverse cardiovascular events
title Glycemic levels and cardiovascular events in type 2 diabetes: A cohort study of drugs with different hypoglycemic potentials
title_full Glycemic levels and cardiovascular events in type 2 diabetes: A cohort study of drugs with different hypoglycemic potentials
title_fullStr Glycemic levels and cardiovascular events in type 2 diabetes: A cohort study of drugs with different hypoglycemic potentials
title_full_unstemmed Glycemic levels and cardiovascular events in type 2 diabetes: A cohort study of drugs with different hypoglycemic potentials
title_short Glycemic levels and cardiovascular events in type 2 diabetes: A cohort study of drugs with different hypoglycemic potentials
title_sort glycemic levels and cardiovascular events in type 2 diabetes a cohort study of drugs with different hypoglycemic potentials
topic Diabetes
HbA1c
Mortality
Major adverse cardiovascular events
url https://doi.org/10.1038/s41598-025-10215-7
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