Insulin Degludec Once-Daily in Type 2 Diabetes: Simple or Step-Wise Titration (BEGIN: Once Simple Use)

Abstract

IntroductionInsulin degludec (IDeg) is a new basal insulin in development with a flat, ultra-long action profile that may permit dosing using a simplified titration algorithm with less frequent self-measured blood glucose (SMBG) measurements and more simplified titration steps than currently available basal insulins.MethodsThis 26-week, multi-center, open-label, randomized, treat-to-target study compared the efficacy and safety of IDeg administered once-daily in combination with metformin in insulin-naïve subjects with type 2 diabetes using two different patient-driven titration algorithms: a “Simple” algorithm, with dose adjustments based on one pre-breakfast SMBG measurement (n = 111) versus a “Step-wise” algorithm, with adjustments based on three consecutive pre-breakfast SMBG values (n = 111). IDeg was administered using the FlexTouch® insulin pen (Novo Nordisk A/S, Bagsværd, Denmark), with once-weekly dose titration in both groups.ResultsGlycosylated hemoglobin (HbA1c) decreased from baseline to week 26 in both groups (−1.09%, IDegSimple; −0.93%, IDegStep-wise). IDegSimple was non-inferior to IDegStep-wise in lowering HbA1c [estimated treatment difference (IDegSimple − IDegStep-wise): −0.16% points (−0.39; 0.07)95% CI]. Fasting plasma glucose was reduced (−3.27 mmol/L, IDegSimple; −2.68 mmol/L, IDegStep-wise) with no significant difference between groups. Rates of confirmed hypoglycemia [1.60, IDegSimple; 1.17, IDegStep-wise events/patient year of exposure (PYE)] and nocturnal confirmed hypoglycemia (0.21, IDegSimple; 0.10, IDegStep-wise events/PYE) were low, with no significant differences between groups. Daily insulin dose after 26 weeks was 0.61 U/kg (IDegSimple) and 0.50 U/kg (IDegStep-wise). No significant difference in weight change was seen between groups by week 26 (+1.6 kg, IDegSimple; +1.1 kg, IDegStep-wise), and there were no clinically relevant differences in adverse event profiles.ConclusionIDeg was effective and well tolerated using either the Simple or Step-wise titration algorithm. While selection of an algorithm must be based on individual patient characteristics and goals, the ability to attain good glycemic control using a simplified titration algorithm may enable patient empowerment through self-titration, improved convenience, and reduced costs.

Cost-effectiveness of Insulin Degludec Versus Insulin Glargine in Adults with Type 1 and Type 2 Diabetes Mellitus

“…In this re-evaluation, a number of revisions were made to the modelling framework. As a consequence of the ultra-long duration of action, flat and stable action profile [10, 11], and lower variability over the day than IGlar U100 [12], there is evidence to suggest that titration and maintenance with IDeg is possible with fewer weekly SMBG tests [43]. Cost savings may therefore be made through the use of fewer SMBG tests with IDeg; however, a change in testing behaviour may take time to translate into clinical practice, so it was excluded from this re-evaluation.…”

Evaluation of the cost-utility of insulin degludec vs insulin glargine in Sweden

“…The flat, stable pharmacokinetic profile of degludec is associated with lower day-to-day glycemic variability than glargine, and therefore the frequency of SMBG testing can be reduced 21 . Therefore, the present analysis has assumed that, in patients with T2D, degludec is associated with a reduced frequency of SMBG tests compared to glargine.…”

“…During the initial titration period it is recommended that patients with T2D receiving insulin degludec conduct twice weekly SMBG to enable appropriate dose titration. At steady state, SMBG testing can be reduced to once weekly 21 . However, once daily testing is still recommended in patients with type 1 diabetes receiving degludec.…”

Insulin Degludec, a Long-Acting Once-Daily Basal Analogue for Type 1 and Type 2 Diabetes Mellitus

“…The dose can be increased or decreased by 2 units (1 click if using the prefilled FlexTouch pen) if glucose is above or below this range. The proposed approach is similar to a simple, once-weekly titration method that was recently described (29).…”