Switching to Degludec is Associated with Reduced Hypoglycaemia, Irrespective of Definition Used or Patient Characteristics: Secondary Analysis of the ReFLeCT Prospective, Observational Study

Abstract

Introduction: Hypoglycaemia is a common side effect of insulin therapy; low or high glycated haemoglobin (HbA1c) levels, history of hypoglycaemia or long diabetes duration are known modifiers of hypoglycaemia risk. In randomised clinical trials, lower rates of hypoglycaemia have been observed with the new-generation insulin analogue, long-acting insulin degludec, compared with other basal insulins.

Methods: The ReFLeCT study was a prospective observational study over 12 months. Patient-reported diary data on hypoglycaemia were collected from patients with type 1 diabetes (T1D) or type 2 diabetes (T2D) who were switching from other basal insulins to insulin degludec (degludec) at their physician's discretion in routine clinical care. Two secondary analyses were undertaken to investigate the change in number of hypoglycaemic events: a post hoc analysis using the updated American Diabetes Association (ADA) level 1, 2 and 3 hypoglycaemia definitions, and a pre-specified analysis using patient characteristics (baseline HbA1c, diabetes duration, and physician's rationale for initiating degludec).

Results: Switching to degludec was associated with significantly fewer hypoglycaemic events for all definitions in T1D, and level 1 and 2 in T2D (too few level 3 events for statistical comparison). Moreover, patient characteristics did not influence the observed reduction in hypoglycaemia in T1D and T2D.

Conclusion: These results demonstrate that switching to degludec from other basal insulins was associated with reduced rates of hypoglycaemia, irrespective of the definition used or baseline patient characteristics.

Trial registration: NCT02392117.

Keywords: Basal insulin; Hypoglycaemia; Insulin degludec; Type 1 diabetes; Type 2 diabetes.

Figures

Fig. 1

Rate ratios of hypoglycaemia according to updated hypoglycaemia definitions in patients with a T1D and b T2D. *p < 0.05; **p < 0.001. †Severe hypoglycaemia, an episode requiring the assistance of another person to actively administer carbohydrate, glucagon or take other corrective actions. a Models were adjusted for period (pre/post-switch to degludec), baseline HbA1c, gender, BMI, duration of diabetes, age and country. Total follow-up time (patient-years) was 38.5 for the 4-week baseline period and 104.5 for the 12-month follow-up period. b Models were adjusted for period (pre/post-switch to degludec), baseline HbA1c, gender, BMI, duration of diabetes, bolus insulin (Yes/No), sulfonylureas or glinides (Yes/No), age and country. Total follow-up time (patient-years) was 40.8 for the 4-week baseline period and 118.8 for the 12-month follow-up period. % percentage of patients with an event, ADA American Diabetes Association, BMI body mass index, CI confidence interval, E number of events, R rate of events per patient-year of exposure, N number of patients with an event, T1D type 1 diabetes, T2D type 2 diabetes

Fig. 2

Rate ratios of overall hypoglycaemia in patients with a T1D and b T2D. *p < 0.05; **p < 0.001; †p values relate to a test for an interaction between period and patient characteristics for overall hypoglycaemia. Analysed using negative binomial regression models. a Models were adjusted for period (pre/post-switch to degludec) baseline HbA1c, gender, BMI, duration of diabetes, age and country. b Models were adjusted for period (pre/post-switch to degludec), baseline HbA1c, gender, BMI, duration of diabetes, bolus insulin (Yes/No), sulfonylureas or glinides (Yes/No), age and country. The rate ratio represents the change in the 12-month follow-up period rate compared with the 4-week baseline period rate, with the significance of a test of the hypothesis that rate ratio = 1 indicated by asterisks. Based on patient diary periods with 26–30 days. % percentage of patients with an event, BMI body mass index, CI confidence interval, E number of events, n number of patients included in fully adjusted analyses, N number of patients with an event, R rate of events per patient-year of exposure, T1D type 1 diabetes, T2D type 2 diabetes