Effects of insulin degludec and insulin glargine U300 on glycaemic stability in individuals with type 1 diabetes: A multicentre, randomized controlled crossover study

Abstract

To compare the effects of insulin degludec (IDeg) and insulin glargine U300 (IGlarU300) on glycaemic stability in subjects with type 1 diabetes. Materials and methods: In this multicentre, crossover trial, 46 individuals with type 1 diabetes and essentially undetectable circulating C-peptide were randomly assigned to either the IDeg-first/IGlarU300-second group or the IGlarU300-first/IDeg-second group, and were treated with the respective basal insulins for 4-week periods. Data were collected in the last week of each treatment period. The primary aim was to examine the potential non-inferiority of IDeg relative to IGlarU300 with regard to dayto-day variability, as evaluated by the standard deviation (SD) of fasting blood glucose (FBG) levels. Intra-day glycaemic variability and other variables were also determined by continuous glucose monitoring (CGM). Results: The SD of FBG for IDeg was non-inferior to that for IGlarU300. The mean of FBG, coefficient of variation of FBG, and various glycaemic variability indexes determined by CGM did not differ between the two insulins. Whereas the administered doses of the insulins also did not differ, the mean glycaemic value was lower for IDeg than IGlarU300; the time above the target range (>180 mg/dL [10.0 mmol/L]) and the time below the target range (<70 mg/dL [3.9 mmol/L]) were shorter and longer, respectively, for IDeg than IGlarU300. Conclusions: Our data suggest that IDeg and IGlarU300 have comparable glucosestabilizing effects in individuals with type 1 diabetes. However, the glucose-lowering effect of IDeg may be greater than that of IGlarU300 when titrated with a unit-based protocol. K E Y W O R D S basal insulin, clinical trial, continuous glucose monitoring, insulin therapy, type 1 diabetes 1 | INTRODUCTION Evidence suggests that, not only hyperglycaemia, but also the fluctuation and variability of glycaemia are related to the development of complications of diabetes. 1-8 Increased glycaemic variability is associated with a risk of hypoglycaemia, 9 which also contributes to the development of various health problems related to diabetes. 10,11 Minimization of glycaemic variability is thus an important issue in the choice of treatment for diabetes.

Effectiveness and Safety of Insulin Glargine 300 U/ml in Comparison with Insulin Degludec 100 U/ml Evaluated with Continuous Glucose Monitoring in Adults with Type 1 Diabetes and Suboptimal Glycemic Control in Routine Clinical Practice: The OneCARE Study

“…Limited evidence is available in the T1D population using CGM and about the comparison between first-and second-generation basal insulins and between the two second-generation basal insulins. A current study conducted by Miura et al comparing the effects of IDeg and Gla-300 on glycemic stability in T1D patients using CGM concluded that both insulins were comparable in terms of glucose-stabilizing effects [23]. These results were also observed in terms of glycemic control in the type 2 diabetes (T2D) population when comparing Glar-300 and IDeg using a CGM device [24].…”

“…The results regarding pharmacodynamics vary. Recently, Miura et al reported the effects of both insulins on glycemic stability in c-peptide-negative T1D patients using CGM [23]. In a multicenter randomized crossover design including 46 patients, the authors suggested that Glarg-300 and IDeg-100 have comparable stabilizing effects on the glucose profile.…”

Effects of Switching from Degludec to Glargine U300 in Patients with Type 1 Diabetes Having Large Day-to-Day Glycemic Variability: A Retrospective Study

“…However, another double-blind crossover euglycemic clump study showed that Deg exhibited lower day-to-day and withinday GV than that of Gla-300 in type 1 diabetes [28]. Recently, Miura et al conducted multicenter crossover trial on type 1 diabetes in which the e ciency of Deg and Gla-300 were compared [29]. In this study, SD-FBG by CGM were evaluated as the marker of day-to-day GV.…”

Insulin and insulin analogs as antidiabetic therapy: A perspective from clinical trials

“…In clinical studies with patients with T1D, degludec has shown reduced risk for hypoglycemia while inducing similar glycemic control as compared to glargine U100 (Heller et al, 2012). When compared to glargine U300, degludec has shown a similar glucose-lowering effect in this patient population (Miura et al, 2020). Given its prolonged effect, degludec allows increased flexibility in the timing of administration, but it may impose a challenge in the inpatient setting where there is a need for faster dose titration.…”