Goyal MK, Hatwal J, Desai R, Sehgal T, Batta A. Glycated hemoglobin and cardiovascular risk in diabetes mellitus: Evolving evidence beyond glycemic control. World J Diabetes 2026; 17(6): 115820 [DOI: 10.4239/wjd.115820]
Corresponding Author of This Article
Akash Batta, DM, MD, Assistant Professor, Department of Cardiology, Dayanand Medical College and Hospital, Tagore Nagar, Civil Lines, Ludhiana 141001, Punjab, India. akashbatta02@gmail.com
Research Domain of This Article
Cardiac & Cardiovascular Systems
Article-Type of This Article
review-article
Open-Access Policy of This Article
This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Manjeet Kumar Goyal, Department of Internal Medicine, Cleveland Clinic Akron General Hospital, Akron, OH 44308, United States
Juniali Hatwal, Department of Internal Medicine, Post Graduate Institute of Medical Education and Research, Chandigarh 160012, India
Rupak Desai, Department of Outcomes Research, Independent Researcher, Atlanta, GA 30033, United States
Tanisha Sehgal, Department of Medicine, Dayanand Medical College and Hospital, Ludhiana 141001, Punjab, India
Akash Batta, Department of Cardiology, Dayanand Medical College and Hospital, Ludhiana 141001, Punjab, India
Author contributions: Goyal MK performed the literature review and data collection; Goyal MK and Batta A designed the review, wrote the manuscript and subsequently revised it; Hatwal J, Desai R and Sehgal T supervised the manuscript and provided key feedback and suggestions; all authors have read and approved the final manuscript.
Conflict-of-interest statement: All authors declare no conflict of interest in publishing the manuscript.
Corresponding author: Akash Batta, DM, MD, Assistant Professor, Department of Cardiology, Dayanand Medical College and Hospital, Tagore Nagar, Civil Lines, Ludhiana 141001, Punjab, India. akashbatta02@gmail.com
Received: October 27, 2025 Revised: November 24, 2025 Accepted: January 8, 2026 Published online: June 15, 2026 Processing time: 228 Days and 7.8 Hours
Abstract
Glycated hemoglobin (HbA1c) remains the cornerstone biomarker for long-term glycemic control in diabetes mellitus, reflecting average plasma glucose over approximately three months. Beyond its diagnostic and monitoring utility, HbA1c has emerged as a robust predictor of cardiovascular disease, the leading cause of morbidity and mortality in individuals with diabetes. Epidemiological studies, including the United Kingdom Prospective Diabetes Study (UKPDS) and the Diabetes Control and Complications Trial, have consistently demonstrated a graded, near-linear relationship between HbA1c levels and macrovascular risk. However, the translation of glycemic control into cardiovascular benefit has proven complex. While early intensive glycemic control confers long-term cardiovascular protection, a phenomenon termed “metabolic memory” later trials such as ACCORD, ADVANCE, and VADT have highlighted the limitations and potential risks of aggressive HbA1c lowering, particularly in high-risk populations. Emerging evidence suggests that HbA1c variability, rather than mean levels alone, may independently contribute to cardiovascular outcomes through mechanisms involving oxidative stress, endothelial dysfunction, and inflammation. Furthermore, contemporary glucose-lowering therapies, including sodium-glucose transporter 2 inhibitors and glucagon-like peptide-1 receptor agonists, reduce cardiovascular events largely independent of HbA1c reduction, challenging the primacy of HbA1c as a surrogate endpoint. This review critically appraises the evolving role of HbA1c in cardiovascular risk stratification, emphasizing the need for individualized glycemic targets and a broader, multifactorial approach to cardiovascular risk reduction in diabetes.
Core Tip: Glycated hemoglobin (HbA1c) is a well-established marker of chronic glycemia and a predictor of cardiovascular risk in diabetes, yet its role as a therapeutic target for reducing cardiovascular events is increasingly nuanced. Evidence from landmark trials highlights both the benefits of early glycemic control and the limitations of intensive HbA1c reduction in advanced disease. Glycemic variability and emerging cardioprotective therapies further challenge HbA1c-centric paradigms. Clinicians should interpret HbA1c within a broader cardiometabolic framework, integrating patient-specific factors and adjunctive risk modifiers to optimize outcomes. A shift from glucose-centric to outcome-driven strategies is essential for contemporary diabetes care.
