Efficacy and Safety of Insulin Degludec in a Flexible Dosing Regimen vs Insulin Glargine in Patients With Type 1 Diabetes (BEGIN: Flex T1): A 26-Week Randomized, Treat-to-Target Trial With a 26-Week Extension

Abstract

Objective:This study investigated the efficacy and safety of insulin degludec (IDeg) once daily (OD), varying injection timing day to day in subjects with type 1 diabetes.Research Design and Methods:This 26-week, open-label, treat-to-target, noninferiority trial compared IDeg forced flexible (Forced-Flex) OD (given in a fixed schedule with a minimum 8 and maximum 40 hours between doses) with IDeg or insulin glargine (IGlar) given at the same time daily OD. In the 26-week extension, all IDeg subjects were transferred to a free-flexible (Free-Flex) regimen, which allowed any-time-of-day dosing, and compared with subjects continued on IGlar.Results:After 26 treatment weeks, mean glycosylated hemoglobin was reduced with IDeg Forced- Flex (−0.40%), IDeg (−0.41%), and IGlar (−0.58%). IDeg Forced-Flex noninferiority was achieved. Fasting plasma glucose reductions were similar with IDeg Forced-Flex and IGlar but greater with IDeg (−2.54 mmol/L) than IDeg Forced-Flex (−1.28 mmol/L) (P = .021). At week 52, IDeg Free-Flex subjects had similar glycosylated hemoglobin but greater fasting plasma glucose reductions than IGlar subjects (−1.07 mmol/L) (P = .005). Confirmed hypoglycemia rates (plasma glucose <3.1 mmol/L or severe hypoglycemia) were similar at weeks 26 and 52. Nocturnal confirmed hypoglycemia was lower with IDeg Forced-Flex vs IDeg (37%; P = .003) and IGlar (40%; P = .001) at week 26 and 25% lower with IDeg Free-Flex vs IGlar (P = .026) at week 52.Conclusions:IDeg can be administered OD at any time of day, with injection timing varied without compromising glycemic control or safety vs same-time-daily IDeg or IGlar. This may improve basal insulin adherence by allowing injection-time adjustment according to individual needs.

Efficacy and safety of insulin degludec in Japanese patients with type 1 and type 2 diabetes: 24‐week results from the observational study in routine clinical practice

“…In a previous phase III clinical study comparing insulin degludec with insulin glargine in a basal–bolus regimen, the degludec group showed a reduced frequency of hypoglycemia, particularly at night, while showing non‐inferiority to glargine in its blood glucose‐lowering effect13, 17. In a subsequent long‐term observational study, the basal and total insulin doses were lower in the degludec group compared with the glargine group18.…”

Inpatient hyperglycemia management: the opportunities of a new basal insulin

“…The greater mean total daily insulin dose with IGlar vs IDeg Free-Flex was due mainly to a decrease in mean daily bolus insulin dose with IDeg Free-Flex (0.39 to 0.35 U/kg) and an increase with IGlar (0.40 to 0.42 U/kg). 22 The nocturnal confirmed hypoglycemia rate was significantly lower with IDeg Forced-Flex than IGlar . Full-year results confirmed findings from the 26-week main trial, with the extension allowing all IDeg subjects the option to dose more flexibly than at same time daily.…”

“…investigated the efficacy and safety of IDeg once daily (OD), varying injection timing day to day in 493 subjects with type 1 diabetes. This was a novel trial both for investigators and participants because it challenged deeply ingrained habits by asking people with long-standing T1DM to inject basal insulin at varying daily time points while simultaneously aim- 22 The proportion of participants who attained pre-breakfast self-monitoring plasma glucose <5.0 mmol/L at week 52 was 17.9% (IDeg Free-Flex) and 13.8% (IGlar). At week 52, mean daily basal, bolus, and total insulin doses were lower by 4%, 18%, and 11%, respectively, with IDeg Free-Flex vs IGlar.…”

“…Full-year results confirmed findings from the 26-week main trial, with the extension allowing all IDeg subjects the option to dose more flexibly than at same time daily. 22 This concept of flexibility was also tested in patients with T2DM and the large variation in the injection time of IDeg did not compromise its efficacy or safety when compared to IGlar taken at the same time each day. 23 Anticipating or delaying a scheduled daily dose of basal insulin will affect its concentration in the circulation; however, this effect will be less for insulin preparations, such as IDeg, with a longer half-life and duration of action.…”

New Long-Acting Basal Insulins: Does Benefit Outweigh Cost?

“…It remains to be seen whether a reduction in the dose of short-acting insulin or other hypoglycemic agents may abolish this untoward daytime hypoglycemia risk. This adaptation may, however, result in a loss of superiority in terms of efficacy compared with standard insulin glargine and perhaps unmask an insufficient efficacy at peripheral muscle and adipose tissues, as might be evidenced by increased lipolysis and some loss of body weight (19,50,51,57). This aspect clearly needs more evaluation, especially since 1 unit of insulin PegLispro contains 9 nmol insulin in contrast to 6 nmol in insulins degludec or glargine U300.…”