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.

Trial registration: ClinicalTrials.gov NCT01079234.

Figure 1.

Glycemic efficacy: mean HbA_1c ± SEM over time (A) and mean FPG ± SEM over time (B). Plotted data are reported mean values for all randomized participants (FAS). Estimated treatment differences are based on FAS. Last observation carried forward is used for each postbaseline time point in A and B. Subjects randomized to the IDeg Forced-Flex and IDeg treatment arms during the main trial period had the opportunity to continue in the IDeg Free-Flex arm after 26 weeks of treatment.

Figure 2.

Hypoglycemia over time, weeks 0–52: severe hypoglycemia (A); overall confirmed hypoglycemia (B); and nocturnal confirmed hypoglycemia (C). Cumulative event rates are based on safety analysis set. Percentage risk reductions refer to delta risks based on estimated rate ratios (FAS). Subjects randomized to the IDeg Forced-Flex and IDeg treatment arms during the main trial period had the opportunity to continue in the IDeg Free-Flex arm after 26 weeks of treatment.