Time in Tight Range: A New Frontier in Glycemic Control or Just a Tighter Time in Range? A Narrative Review

Abstract

Background/Objectives: Continuous glucose monitoring (CGM) has transformed diabetes management, with time in range (TIR) emerging as a key glycemic metric. However, TIR lacks sensitivity to glycemic variability, leading to the introduction of time in tight range (TiTR), which defines a narrower range (70–140 mg/dL). This review synthesizes current evidence on TiTR’s clinical relevance and its potential to predict complications. Methods: A literature search was conducted, primarily using PubMed as the main database, to identify studies that specifically evaluate TiTR and its clinical implications, published until February 2025. Results: Preliminary data indicate that a 10% increase in TiTR is associated with a 23.8% reduction in microvascular complications. While TiTR aligns more closely with physiological glucose control, standardized targets remain undefined. Conclusions: This study provides clinicians with insights into optimizing glycemic control beyond traditional metrics. The correlation of TiTR with other glycemic markers and its association with diabetes-related complications suggest that TiTR can complement traditional measures to provide a more comprehensive assessment of glycemic status. From a clinical perspective, incorporating TiTR into routine practice may help personalize treatment strategies, improve risk stratification, and support more precise therapeutic decisions, particularly in patients using continuous glucose monitoring (CGM). Future research should refine TiTR thresholds and evaluate its integration into diabetes management, particularly in populations using advanced technologies.

1. Introduction

Since the introduction of continuous glucose monitoring (CGM) in 1999 with the Medtronic System Gold Continuous Glucose Monitor (Northridge, CA, USA), glucose monitoring systems have evolved to become an essential tool in the daily management of diabetes, including type 1, type 2, and even other forms of diabetes [1,2]. However, the vast amount of data generated daily has posed a significant challenge in clinical interpretation [3].

In this context, the definition of time in range ((TIR): percentage of time an individual spends within a blood glucose range between 70–180 mg/dL) as a key glycemic parameter, comparable to classic markers such as glycated hemoglobin (HbA1c), is relatively recent [2]. Nevertheless, it has rapidly become an integral part of clinical practice.

The advancement of new diabetes technologies, along with the development of innovative pharmacological treatments that have enabled unprecedented metabolic control, has necessitated a reevaluation of glycemic control targets [3]. In this regard, time in tight range (TiTR) has gained increasing importance due to its implications for the general population [4], its impact on outcomes achieved with novel therapies, and the technological advances of the last decade, positioning it as an essential glycemic parameter.

The aim of this review is to assess the scientific evidence supporting the use of TiTR in clinical practice, its relationship with other glycemic markers, and its role in the development of complications, as well as its application in different clinical scenarios.

Methods

This narrative review focuses on time in tight range (TiTR), a novel metric for glycemic control that is gaining increasing importance in diabetes management. It analyzes the scientific evidence supporting TiTR, examines its relationship with other glycemic markers, and explores its role in diabetes-related complications. A literature search was conducted using PubMed and Scopus to identify studies evaluating TiTR and its clinical implications, up to February 2025. The search terms used in PubMed were: “TiTR” and “Time in Tight Range”.

2. Limitations of TIR

TIR has been recently incorporated into clinical guidelines following the publication of the international consensus TIR in 2019 [2]. In fact, the American Diabetes Association (ADA) has recognized the need for its measurement and, consequently, recommends the use of CGM in all patients with type 1 and type 2 diabetes (T2D), regardless of their treatment, to assess glycemic control at the same level as HbA1c [1]. Therefore, TIR has been established as a key metabolic control variable and has recently been linked to both microvascular and macrovascular complications [5]. The proposed metabolic control target for TIR in the general population is >70% (

Table 1. Recommendations for time in range (TIR) international consensus.

Category	Target Range	TIR Target	High Glucose (>180 mg/dL)	Very-High Glucose (>250 mg/dL)	Low Glucose (<70 mg/dL)	Very-Low Glucose (<54 mg/dL)
Type 1 & Type 2 Diabetes	70–180 mg/dL (3.9–10.0 mmol/L)	>70%	<25%	<5%	<4%	<1%
Older/High-Risk: Type 1 & Type 2 Diabetes	70–180 mg/dL (3.9–10.0 mmol/L)	>50%	<50%	<10%	<1%	<1%

) [2]. What is more, it has been suggested that TIR could replace HbA1c as the primary glycemic parameter due to the limitations of HbA1c in conditions such as hemoglobinopathies, altered erythrocyte turnover, dialysis, and pregnancy, among others [1].

However, TIR has certain limitations. It lacks sufficient sensitivity in detecting hypoglycemia and extreme glycemic values, such as TAR (>250 mg/dL) and TBR (<54 mg/dL). Moreover, time in range (TIR) treats all values outside the target range as equally significant, without differentiating their severity. It does not reflect glycemic variability and, in some cases, presents a significant discrepancy between HbA1c levels and TIR, making interpretation challenging. TIR only provides insight into the centrality of glycemic control without accounting for glucose variability [6,7].

Additionally, new therapies have made it possible to achieve higher TIR levels than those recommended by clinical guidelines, without increasing the risk of hypoglycemia. In this context, it seems logical to explore new parameters that can synthesize existing data and help healthcare professionals set stricter goals for diabetes management.

3. TITR Definition, Physiological Basis, and Therapeutic Goals

TiTR is defined as the time an individual maintains blood glucose levels between 70 and 140 mg/dL [4]. Unlike the target range established by consensus for TIR, which is primarily based on its relationship with the goal of 7% HbA1c, TiTR partially derives its control targets from those observed in healthy populations [8]. In fact, this CGM correlation with normoglycemia has been proposed for defining the different stages of diabetes, and it is essential for evaluating the effectiveness of new immunomodulatory treatments in type 1 diabetes (T1D) [9].

CGM studies by Shah et al. have shown that the average time spent between 70 and 140 mg/dL in a cohort of 153 healthy subjects corresponds to a TiTR of 96% (93–98% IQR), with 85% of individuals having less than 5% of values above 140 mg/dL. In fact, healthy individuals spent most of the time within the 70–140 mg/dL range, with occasional excursions between 140 and 180 mg/dL occurring only for short periods after meals [8]. Thus, TiTR mitigates the limitations of TIR by providing a better reflection of glycemic variability, as it narrows the glucose target range and improves correlation with the physiological glucose control observed in healthy individuals. This approach offers a more precise evaluation of glycemic outcomes beyond HbA1c.

Thus, the commonly used TIR threshold of 70% is far from the physiological range observed in healthy individuals. Advances in technology and new treatments for T2D are making it increasingly possible to achieve glucose levels closer to normoglycemia or euglycemia.

3.1. TITR Therapeutic Goals

So far, no definitive TiTR target has been established. However, initial studies have proposed desirable TiTR levels to define good metabolic control and establish equivalencies between TiTR levels and HbA1c values. The first definition of a TiTR target in an international consensus was likely established preliminarily in Continuous Glucose Monitoring and Metrics for Clinical Trials by Battelino et al. [4], where it was set as TiTR > 70%, probably just by analogy with TIR > 70%, particularly for those T2D patients using glucose-lowering agents and T1D patients using automatic hybrid closed-loop (AHCL) systems. However, recent studies have analyzed the plausibility of these targets in populations with diabetes and their relationship with classical metabolic control parameters, and consequently, the risk of developing chronic complications.

In this context, a TiTR above 50% has been considered a reasonable and safe treatment goal for patients with T1D (adults and pediatrics). In fact, according to Peterson, a TiTR of 50% correlates with an HbA1c level of 6.5% [10].

More recently, Castañeda et al. have proposed new TiTR targets to guide treatment strategies for individuals with T1D, raising the possibility of redefining current standards [11]. Their findings highlight the correlations with HbA1c (Table 1).

These findings suggest the need for further exploration of the relationship between TiTR, HbA1c, and glucose management indicator (GMI) to define more precise and clinically relevant therapeutic goals for diabetes management. However, while awaiting a consensus that definitively defines TITR, TiTR > 50% seems to be a reasonable target in the population with diabetes [12].

However, until automated glucose pattern analysis systems become commercially available, it remains uncertain whether it is feasible or even desirable to establish a uniform time in range target for nighttime, daytime, or even postprandial periods. A recent study, including 56 participants under 18 years old using the MM780G system, found that most children and adolescents successfully met the >50% target, with 87% achieving this threshold and 52% exceeding 60%. What is more, values were higher at night and in individuals with fewer autocorrections (<30%), suggesting potential advantages in glycemic stability during nighttime [13].

3.2. TITR and Its Relationship with Other Glycemic Variables

3.2.1. TITR and TIR

The relationship between time in range (TIR) and time in tight range (TiTR) has been previously analyzed due to its potential clinical implications [12,14]. While a few studies have demonstrated a strong positive correlation between these two metrics (r  =  0.849, p  <  0.001) [12], recent findings by Beck et al. suggest that this relationship changes at the extremes, particularly in individuals approaching normoglycemia [14]. This non-linear relationship may, in the future, contribute to a better prediction of complications in individuals with strict metabolic control [12]. Furthermore, TiTR is, on average, 20–25% lower than TIR when GMI falls between 6–8% across various cohorts and treatment types. Additionally, the gap between TiTR and TIR decreases as GMI values rise, suggesting a progressive convergence of these two glycemic metrics with increasing GMI levels [15].

3.2.2. TITR and Coefficient of Variation (CV)

One of the key limitations of time in range (TIR) and time in tight range (TiTR) is their low sensitivity to changes in glycemic variability. This limitation is not unique to these metrics but is also observed in traditional centrality measures, including HbA1c [16]. Glycemic variability itself remains challenging to quantify, despite being recognized as an important parameter in diabetes management.

Current clinical guidelines and glucose profiling strategies recommend assessing glycemic variability through the coefficient of variation (CV), with a threshold of 36% as a clinically relevant cutoff [2]. Several studies have analyzed the relationship between CV and TiTR, highlighting how higher CV values influence TiTR and TIR dynamics [12,15,17]. In general, the greater the CV, the higher the TiTR corresponding to a given TIR, since increased glucose variability results in a wider glucose range, often leading to a lower overall TIR. Bahillo et al. [12] analyzed the impact of CV on TiTR and TIR. Their findings showed that when the CV was greater than 36%, a TIR of 70% corresponded to a TiTR of 47.9%. However, when the CV was less than 36%, the TiTR decreased to 42.0% for the same TIR of 70% [12]. Beck et al. [14] studied 1096 individuals with type 1 and T2D (ages 2–83) using CGM with Dexcom sensors [14]. Their analysis found that differences in the TIR-TiTR relationship across diabetes types (T1D vs. T2D) disappeared after adjusting for CV and TBR. Higher CV and TBR values were associated with higher TiTR for a given TIR. For a TIR of 70%, the expected TiTR was 45%, but varied significantly; 38% when CV was <32% and 49% when CV exceeded 40%. Xu et al., 2024 further confirmed that CV plays a significant role in the relationship between mean glucose, TIR, and TiTR, reinforcing the importance of glucose variability as a factor influencing glycemic targets [17].

These findings suggest that higher glucose variability (higher CV) can artificially increase TiTR values while simultaneously reducing TIR. This emphasizes the need to consider CV when interpreting TiTR in clinical practice, as it may impact the reliability of TiTR as a glycemic control metric [12].

3.3. TITR in Real Life

Some recent studies have analyzed the achieved TiTR targets in real-world populations. In general, patients with a shorter disease duration, those with T2D receiving new therapies, and those with T1D using AHCL are the most likely to achieve the proposed TiTR targets [4].

Beck et al. (2024) [14]: Examined TiTR in pediatric and adult populations (ages 2–83) with T1D. The average TiTR was 53% in AHCL (Tandem Control IQ) users compared to 32% in non-users [14]. TIR levels were 71% in AHCL users versus 47% in non-users. Similarly, Bahillo et al. (2024) reported a TiTR of 40.4% in adults and 48% in children before AHCL initiation. After AHCL use, TiTR increased to 53.7% in adults and 62.7% in children [12].

One of the most relevant and earliest real-world studies assessing TiTR exclusively in a pediatric population included 854 children using different treatment modalities, including multiple daily injections (MDIs) + continuous glucose monitoring (CGM), MDIs + intermittent scanned glucose monitoring (isMCG), sensor-augmented pumps (SAPs), and AHCL systems (MM780G + Control IQ) [18]. The study analyzed TiTR in these four groups, reporting an average TiTR of 36.4% ± 12.8% across the entire sample, with an overall TIR of 59%. The highest TiTR values were observed in AHCL users, showing 45% ± 11.2% (TIR 70%), followed by SAP: TiTR 36.2% ± 11% (TIR 59%), MDIs + MCG: TiTR 34.2% ± 12.3% (TIR 57%) and MDIs + MFG: TiTR 28% ± 10.6% (TIR 46%). Regarding TiTR ≥ 50%, 34.3% of children using AHCL reached this target, while only 17% of the total sample achieved it. Notably, just 1.2% of the participants had TiTR > 70%.

Similarly, a study conducted across 28 pediatric centers included 613 patients aged 6 to 18 years, using either MM780G (57.3%) or Tandem t:slim X2™ Control IQ (46.3%) systems [19]. The average TiTR was 47.4% ± 11.8%, with 43.9% of patients achieving TiTR > 50%. When comparing the two systems, MM780G users had a statistically higher TiTR of 51.1% but Tandem t:slim X2™ Control IQ users had a TiTR of 43.3% (p < 0.001). The study also found that time spent in automatic mode and the number of different carbohydrate ratios were significant predictors of TiTR, even after adjusting for age, diabetes duration, sex, BMI Z-score, and total daily insulin dose.

Finally, a retrospective real-world-based study analyzed TiTR in 13,461 users of the MiniMed 780G (MM780G) system, examining its relationship with time in range (TIR) (70–180 mg/dL), factors predicting higher TiTR, and determining a reasonable TiTR treatment goal [20]. The study found that the average TiTR was 48.9% in users ≤ 15 years old and 48.8% in those >15 years old, compared to TIR levels of 71.2% and 73.9%, respectively. The strongest predictors of higher TiTR were consistent use of a glucose target of 100 mg/dL and an active insulin time of 2 h (p < 0.0001). Users who consistently applied these optimal settings achieved TiTR levels of 56.7% (≤15 years) and 57.0% (>15 years), showing that the impact of these settings on TiTR was significantly greater than on TIR (60% and 86% higher, respectively) (

Table 2. Correlations between time in tight range (TiTR) and HbA1c. (GMI: glucose management indicator.)

TiTR Threshold	Correlation
>45%	HbA1c < 7% (Undetermined if 45% is the new 70%)
>50%	GMI < 6.8%
>55%	GMI < 6.5%

).

All these findings highlight the superiority of AHCL systems in achieving higher TiTR levels and the importance of optimizing system settings to enhance glycemic outcomes in real-world settings [12,14,18,19,20]. These findings highlight the potential impact of AHCL systems in improving TiTR and TIR values, particularly in pediatric and adult populations with T1D. It is essential to highlight that increases in TiTR occurred without an increase in the time spent between 140 and 180 mg/dL. This indicates that the improvement in TIR was specifically driven by enhancements within the TiTR range, rather than changes in the 140–180 mg/dL range, which is included in the broader TIR metric [12,18].

However, the studies conducted and the available evidence in both MDI therapy and T2D are much more limited. A sub-study of the SURPASS-3 trial assessed TiTR in participants with T2D using tirzepatide (5 mg, 10 mg, or 15 mg) compared with insulin degludec, monitored with continuous glucose monitoring (CGM) over 52 weeks [21]. Patients receiving tirzepatide spent significantly more time in tight range compared to insulin degludec (estimated treatment difference 25%, 95% CI 16–33; p < 0.0001). At 52 weeks, the increase in TiTR compared to insulin degludec ranged between 12% and 25%. Likewise, a recent study in individuals with T1D on MDI supports the use of lower TiTR targets in this population [22]. A TiTR of 41% was identified as the threshold for achieving GMI < 7.0% (sensitivity 81%, specificity 88%), reducing hypoglycemia risk, while 40% TiTR was associated with maintaining TBR < 4% (sensitivity 54%, specificity 72%).

4. TITR for Whom, Current Debate on TiTR vs. TIR in Diabetes Management, Limitations and Strengths

There is an ongoing debate on whether TiTR should replace TIR or simply be incorporated as a standard metric in diabetes assessment. The main criticisms stem from the lack of long-term studies demonstrating a reduction in chronic complications, as well as the fact that most studies focus on optimizing TIR, with high TiTR levels being achieved only incidentally rather than as a primary goal [15,23]. Furthermore, replacing TIR with TiTR could potentially lead to an increase in hypoglycemia and greater frustration among patients who struggle to meet these more stringent targets, without clear evidence that it reduces long-term microvascular or macrovascular complications.

On the other hand, the strong correlation between TIR and TiTR observed in multiple studies suggests that improving one metric inherently leads to improvements in the other. This raises the question of whether replacing TIR with TiTR would offer any additional clinical benefit in terms of reducing chronic complications [15,23].

Despite ongoing debate, the use of TiTR as a metric could offer significant benefits in diabetes management. TiTR better reflects glucose levels closer to normal physiology compared to TIR, making it a valuable indicator for tighter glycemic control. TiTR becomes particularly relevant when normoglycemia is the clinical goal. It has been shown to be more effective than TIR in detecting changes in mean glucose and glycemic variability, especially when mean glucose levels fall below 140 mg/dL. A narrow glycemic control range is essential for certain patient populations, including pregnant women and children, due to their long life expectancy and the impact of metabolic memory. Additionally, TiTR may play a crucial role in early diabetes stages (Stage 2), where stricter glucose targets may help delay disease progression [24] (

Table 3. Target population for time in tight range (TiTR).

Population Group	Relevance of TiTR
Individuals with Type 1 Diabetes	TiTR may help achieve tighter glucose control, particularly in those using advanced diabetes technology such as hybrid closed-loop systems.
Individuals with Type 2 Diabetes on New Therapies	New treatments allow for glucose levels closer to normoglycemia, making TiTR a valuable metric.
Pregnant Women with Diabetes	Strict glycemic control is essential due to fetal and maternal health concerns, making TiTR particularly relevant.
Children and Adolescents with Diabetes	Long life expectancy and metabolic memory effects support the use of TiTR for better long-term outcomes.
Patients at High Risk of Hypoglycemia	TiTR can provide additional insight into glucose stability without excessive hypoglycemia risk.
Early-Stage Diabetes (Stage 2)/Dysglycemia/Prediabetes	TiTR may help in identifying individuals who could benefit from early interventions to delay disease progression.

).

While TIR and TiTR are complementary metrics, TiTR may be preferable in cases where achieving an HbA1c target below 7% (e.g., 6.5% or 6%) is the primary goal, as TIR becomes less sensitive to changes in mean glucose and glycemic variability at these lower levels.

Another advantage of TiTR is that it helps patients become more aware of and visualize additional glucose excursions above the target range, providing a more detailed perspective on glycemic fluctuations compared to TIR.

5. TITR and Chronic Complications

One of the main criticisms of using TiTR in diabetes management is the lack of long-term evidence demonstrating its impact on chronic complications, making it difficult to justify recommending stricter glucose targets. A few years ago, this same criticism was also directed at TIR. However, the accumulated evidence over recent years has firmly established its clinical utility across various studies [15]. Indirectly, data from the DCCT trial and the Swedish Diabetes Registry suggest that glucose levels above 180 mg/dL are the primary contributors to diabetes-related complications [6]. This raises an important consideration: glucose levels between 140 and 180 mg/dL may not have a significant impact on complication risk. If this hypothesis is correct, the percentage of time spent above 180 mg/dL might be a better predictor of complications than the percentage of time between 140 and 180 mg/dL.

Despite this hypothesis, emerging research has shown an association between higher TiTR levels and a reduction in both microvascular and macrovascular complications, suggesting its potential role as a meaningful glycemic target in diabetes care. In fact, lower TITR has been associated with an increased risk of all-cause and cardiovascular mortality in patients with T2D, indicating that tight glycemic control within the physiological range may be crucial for reducing long-term mortality risk, especially in those with seemingly well-controlled diabetes [25]. Additionally, TITR has been inversely associated with the incidence of diabetic retinopathy in adults with T2D and T1D, even in well controlled patients evaluated by higher TIR patients [26,27]. More specifically, a 10% increase in TiTR was associated with a 23.8% reduction in microvascular complications [27]. These results provide added value regarding tighter glucose control in diabetic patients.

Table 4. Overview of Principal Studies on time in tight range.

Study	Number of Subjects	Year	Research Methods	Conclusion	Limitations
Shah et al. [8]	153	2019	CGM study on healthy individuals	TiTR in healthy individuals is around 96%	Limited to healthy subjects
Petersson et al. [10]	133	2019	Translating HbA1c to TiTR	TiTR of 50% correlates with HbA1c of 6.5%	Needs validation in different populations
Castañeda et al. [11]	13,461	2024	Analyzing TiTR in diabetes patients	Proposed new TiTR targets for diabetes	Lack of consensus on TiTR target
Bahíllo et al. [12]	117	2024	Studying TiTR in AHCL systems	TiTR levels increase with AHCL use	Limited data on MDI and type 2 diabetes
Eviz et al. [13]	56	2024	Real-world study on AHCL use in children	Majority achieved TiTR >50%, higher values at night	Small sample size, single-center study
Beck et al. [14]	1096	2024	Comparing TiTR with TIR	TiTR is about 20–25% lower than TIR	Non-linear relationship in normoglycemia
Passanisi et al. [18]	854	2024	Evaluating TiTR in pediatric patients	Higher TiTR linked to better control	Focused only on pediatrics
Schiaffini et al. [19]	534	2024	Cross-sectional study on TiTR in children	AHCL systems improve TiTR in children	Single-center observational study on pediatrics
Piona et al. [20]	613	2024	Real-world study on TiTR	Optimal TiTR settings improve outcomes	Cross-sectional real-world study in pediatrics
Cai et al. [25]	6061	2025	Prospective cohort study on TiTR and mortality	Higher TiTR linked to lower mortality risk	Lack of long-term validation
Wang et al. [26]	2518	2024	Association of TiTR with diabetic retinopathy	Higher TiTR associated with lower retinopathy risk	Correlation does not prove causation
De Meulemeester et al. [27]	808	2024	Association of TiTR with chronic complications	Lower TiTR linked to chronic complications	Retrospective study limitations

resumes the scientific publications evaluated to date.

6. Conclusions

TiTR offers a refined approach to glycemic monitoring, addressing limitations of TIR and HbA1c. Its strong correlation with metabolic control parameters and emerging evidence linking higher TiTR levels to reduced complications suggest clinical utility. However, standardized thresholds and long-term studies are needed before full clinical adoption. Future research should assess TiTR’s role in individualized treatment plans and its predictive value in chronic diabetes complications. As diabetes technology advances, TiTR may serve as a crucial tool in achieving near-physiological glycemic control, benefiting both clinicians and patients seeking optimized diabetes management.