Background: Glycated hemoglobin (HbA1c) has long been considered the gold standard for evaluating long-term glycemic control in patients with diabetes mellitus. However, emerging technologies and evolving clinical priorities have led to increasing attention on Time-inRange (TIR), a continuous glucose monitoring (CGM)-derived metric, as a complementary or potentially superior alternative to HbA1c. TIR offers a dynamic assessment of glucose fluctuations, providing granular insights into daily glycemic variability that may be more reflective of real-world glycemic exposure and associated risks. 

Objective: ①This article critically evaluates the role of HbA1c as the longstanding biomarker of glycemic control, its biochemical underpinnings, diagnostic limitations, and its correlation with complications, ② how does TIR, as measure by CGM, compare with HBA1c in predicting glycemic control and long term diabetes complication in individuals with diabetes, ③ moreover It also examines the clinical relevance, interpretation, and potential integration of TIR as a routine clinical metric, while exploring the current limitations, evidence base, and prospects of CGM-based analytics.

Methods: A detailed narrative review was conducted synthesizing historical, biochemical, and clinical evidence supporting the use of HbA1c. Emerging data from international consensus guidelines and landmark studies were analysed to elucidate the clinical utility of TIR. Comparative analyses of TIR and HbA1c were explored using illustrative case studies and CGM reports, with emphasis on glycemic variability, hypoglycemia risk, and patient-centred outcomes. 

A PRISMA flow diagram will be used to report the screening and selection process.

Structured PICO framework 

i. Population (P) Individual with T1, Type 2 Diabetes and Type 1.5 ( LADA) 

ii. Intervention ( I ) TIR measured by CGM 

iii. Comparison (C) glycated Hemoglobin 

iv. Outcome (O) Estimation of glycemic Control, incidence of diabetesrelated complications (e.g., retinopathy, nephropathy, mortality), and clinical decision-making relevance

Systemic search strategy: a structured literature search will be conducted to identify studies comparing TIR and HBA1c for assessing glycemic control and predicting diabetes related complications.

Database of the search: PubMed/MEDLINE, Scopus, Embase, Cochrane Library, and Google Scholar

Search Period Jan 2015-July 2025

Inclusion criteria: Studies including children, adults ( ≥ 18 years) with T1, T2 DM, and LADA; original research, clinical trials, or systematic review: studies comparing TIR and HbA1c in terms of glycemic control and outcomes

Exclusion criteria: Studies focused on gestational diabetes or prediabetes individuals

Secondary research strategy 

1) Does TIR provide a stronger correlation with micro or macrovascular complications compared to HbA1c?

2) Which patients’ populations ( pregnant women, CKD, elderly ) is TIR considered a more reliable metric than HbA1c 

3) What are the methodological or technical limitations of utilizing TIR across different CGM systems in research, as well as in clinical practice

Results: While HbA1c offers a retrospective average of glucose levels over 2–3 months, it fails to capture glycemic excursions and variability, and is influenced by non-glycemic factors such as hemoglobinopathies, renal dysfunction, and erythrocyte turnover. Conversely, TIR provides real-time, actionable data, correlates strongly with microvascular complications, and aligns more closely with patient perception and therapeutic outcomes. Clinical studies suggest a 10% increase in TIR is associated with a significant reduction of 40-64% in microvascular complications like retinopathy, nephropathy, and neuropathy compared to HbA1c alone.

Evidence is emerging, though less robust, that some studies’ TIR may predict macrovascular complications risk (e.g., carotid intima-media thickness, cardiovascular events), but HbA1c remains the established metric in this domain.

Patient population where TIR is considered more reliable; Pregnant women predict better short-term glycemic control, which is critical for fetal outcome. CKD Patients’ HbA1c might be inaccurate due to anemia, uremia, and altered erythrocyte life span, whereas TIR can overcome these confounders. In the elderly population, HbA1c may overestimate control due to age-related changes in the glycation process, while TIR offers more reliable real-time insight and hence avoids hypoglycemia. Despite its promise, TIR lacks universal standardization, and inter-device variability remains a concern. Moreover, robust longitudinal outcome data are still emerging.

Conclusion: While HbA1c remains indispensable for diabetes diagnosis and longitudinal population-level assessment, TIR enhances clinical decisionmaking through its nuanced portrayal of daily glycemic control. Despite its promise, TIR lacks universal standardization, and inter-device variability remains a concern. Moreover, robust longitudinal outcome data are still emerging. TIR should not be viewed as a replacement for HbA1c but rather as a powerful adjunct that facilitates individualized therapy, improves patient engagement, and supports precision medicine in diabetes care. Ongoing efforts in CGM standardization, education, and outcome-based validation are essential before TIR can be universally adopted as a co-primary glycemic metric in clinical guidelines.