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
Tadej Battelino, Zsolt Bosnyak, Thomas Danne, Bhaswati Mukherjee, Steve Edelman, Valerie Pilorget, Pratik Choudhary, Eric Renard, Richard Bergenstal
Abstract Aims: 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.
Methods: InRange is a multicentre, randomised, active-controlled, parallel-group, 12-week, open-label, phase 4, comparative study. Adults with T1D will be randomised to receive once-daily Gla-300 or IDeg-100 by subcutaneous injection in the morning. Following an 8-week titration period, CGM data will be collected over 20 consecutive days.
Planned outcomes: The primary objective is to demonstrate that Gla-300 is noninferior to IDeg-100 in terms of glycaemic control [timein-range C 70 to B 180 mg/dL (C 3.9 to B 10 mmol/L)] and variability, as assessed using CGM, in adults with T1D. The results are expected to help confirm the utility of CGM in clinical practice in this population and provide insight into its application as an outcome measure in clinical practice.
Keywords: Continuous glucose monitoring; Fasting plasma glucose; Glucose variability; Glycated haemoglobin; Insulin; Insulin degludec; Insulin glargine; Self-monitoring of plasma glucose; Time-in-range; Type 1 diabetes.