InRange: Comparison of the Second-Generation Basal Insulin Analogues Glargine 300 U/mL and Degludec 100 U/mL in Persons with Type 1 Diabetes Using Continuous Glucose Monitoring—Study Design

Abstract

Introduction: Suboptimal glycaemic control among people with type 1 diabetes (T1D) is known to lead to long-term micro-and macrovascular complications and, unfortunately, it is still prevalent even in the most affluent societies. Although glycated haemoglobin monitoring is considered to be the gold standard for assessing glycaemic control, such monitoring is unable to reliably measure acute glycaemic excursions. Continuous glucose monitoring (CGM) has been shown to improve glucose control and reduce the incidence of hypoglycaemia, and also allow a more complete assessment of overall glycaemic control and hyper-and hypoglycaemic excursions. The use of CGM has led to time-in-range, which is the time that a patient is within the glycaemic range of 70 to 180 mg/dL, to be adopted as a treatment target. To date, only limited data comparing the second-generation insulins glargine 300 U/mL (Gla-300) and degludec 100 U/mL (IDeg-100) in people with T1D are available, and there is no CGM literature on comparisons of the use of CGM results to assess primary, secondary and tertiary endpoints. The aim of the InRange study was to address this unmet need.

Comparison of Second-Generation Basal Insulin Analogs: A Review of the Evidence from Continuous Glucose Monitoring

“…40 In line with the recent TIR International Consensus Group report, 8 which highlights TIR as the most important CGM metric, the primary endpoint of InRange is percent time spent in the glucose range of ‡70 to £180 mg/dL ( ‡3.9 to £10 mmol/L) at week 12. 40 Conclusions CGM can provide a powerful tool in RCTs studying the efficacy and safety of second-generation basal insulin analogs as it can provide comprehensive data on 24-h blood glucose levels. 8 In this regard, evidence on day-to-day and within-day glycemic variability and acute glycemic excursions may be better captured with CGM compared with HbA 1c and SMBG measurements.…”

“…InRange (NCT04075513) is a 12-week, randomized, open-label, twoarm, parallel group, multicenter study that uses CGM to compare Gla-300 with IDeg in *340 adult participants with T1D. 40 In line with the recent TIR International Consensus Group report, 8 which highlights TIR as the most important CGM metric, the primary endpoint of InRange is percent time spent in the glucose range of ‡70 to £180 mg/dL ( ‡3.9 to £10 mmol/L) at week 12. 40 Conclusions CGM can provide a powerful tool in RCTs studying the efficacy and safety of second-generation basal insulin analogs as it can provide comprehensive data on 24-h blood glucose levels.…”

“…The InRange trial, with its relatively large population and CGM-derived metrics for the primary outcome, will help to provide further evidence for efficacy and safety of head-to-head comparisons of the two second-generation basal insulin analogs, Gla-300 and IDeg. 40 In addition to the potential of CGM for assessment of basal insulins in a trial setting, CGM has also demonstrated significant benefits in the treatment of people with T1D, or with T2D requiring intensive insulin treatment, and is recommended by a number of medical societies. [48][49][50][51][52] The customizable TIR metric obtained using CGM provides a valuable, streamlined measure of glycemic control that can be actively used for daily therapeutic decision-making in clinical practice and has the potential to allow the specific needs of each individual with diabetes to be addressed, including those with gestational diabetes or at high risk, and those for whom HbA 1c measurement may be unreliable.…”

Controlling glycemic variability in people living with type 1 diabetes receiving insulin glargine 300 U/mL (Gla-300)

“…25 There is a lack of longer term prospective studies using CGM and of studies comparing second-generation basal insulin. Upcoming studies, [26][27][28][29] including randomized clinical trials and real-world studies, will add to this body of evidence.…”

“…The eight papers on RCTs related to glycemic variability in people living with T1D receiving Gla-300 reported results for four trials [20][21][22][23][24] and summarized the methodology for another study, for which the results are not yet available. [26][27][28] Three of the completed studies compared Gla-300 with Gla-100 20 21 23 and one compared Gla-300 with insulin degludec U100 (iDeg-100). 22 24 All of the RCTs were open label, with two using a parallel-group design 20 21 and two using a cross-over design.…”