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
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.
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.
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.
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ABSTRACT: Many patients with type 2 diabetes continue to have poor glycaemic control and would benefit from insulin therapy. However, resistance to the introduction of insulin therapy can be high on both the part of the healthcare provider and the patient. A number of new, long-acting basal insulins are in development that provide good metabolic control, but with a lower risk of hypoglycaemia than currently available insulins, and greater flexibility in dosing time from day to day. These attributes may address some of the current barriers to insulin initiation and intensification that currently limit the effectiveness of diabetes care.10/2013; DOI:10.1016/j.pcd.2013.09.003
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ABSTRACT: Aim To evaluate health-related quality of life (health utility) scores in patients with diabetes receiving insulin degludec (IDeg) or insulin glargine (IGlar). Methods Patient-level data from six, randomized, controlled, open-label, multicentre, confirmatory, treat-to-target trials of 26- or 52 weeks' duration were pooled in this analysis. The Short Form 36 (SF-36) version-2 health questionnaire was completed by patients at baseline and end-of-trial. SF-36 scores for 4001 individual patients were then mapped onto the EuroQol-5D health utility scale, which has a range from −0.59 (a state worse than death) to 1.00 (perfect health). Results IDeg treatment exhibited a significant improvement in health status of 0.005 (CI: 0.0006; 0.009) points compared with IGlar (p < 0.024). Gender, region, trial and age also had a significant influence on estimated utility scores as did baseline utility scores, p < 0.05. Prior to the removal of interaction variables a difference of 0.008 points was observed, p < 0.045. Previous insulin treatment did not have an impact on the final outcome. Conclusion This study shows that IDeg is associated with a modest, but statistically significant, improvement in health utility compared with IGlar in patients with diabetes.Diabetes Obesity and Metabolism 03/2013; 15(6). DOI:10.1111/dom.12086 · 5.46 Impact Factor
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ABSTRACT: Insulin degludec (Tresiba(®)) is an ultra-long-acting insulin analogue that is also available as a coformulation with rapid-acting insulin aspart (insulin degludec/insulin aspart) [Ryzodeg(®)]. Insulin degludec has a flat, stable glucose-lowering profile with a duration of action of >42 h, and less within-patient day-to-day variability in glucose-lowering effect than the long-acting insulin analogue insulin glargine. In clinical trials, insulin degludec achieved similar glycaemic control to that seen with insulin glargine in patients with type 1 or 2 diabetes, but with a lower risk of nocturnal hypoglycaemia. In addition, trials examining a flexible dosing regimen of insulin degludec in patients with type 1 or 2 diabetes show the potential for adjusting the injection time, without compromising glycaemic control or safety. A 200 U/mL formulation of insulin degludec is also available for use in patients who require large volumes of basal insulin. Insulin degludec/insulin aspart was noninferior to the long-acting insulin analogue insulin detemir in patients with type 1 diabetes and has the potential to reduce the number of daily injections. Trial results also indicate that insulin degludec/insulin aspart may be an appropriate option for initiating insulin therapy in patients with type 2 diabetes inadequately controlled with oral antidiabetic drugs. Subcutaneous insulin degludec was generally well tolerated in patients with type 1 or 2 diabetes. In conclusion, insulin degludec and insulin degludec/insulin aspart represent a useful advance in the treatment of type 1 or 2 diabetes.Drugs 04/2013; 73(6). DOI:10.1007/s40265-013-0051-1 · 4.13 Impact Factor