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Phase 2 Clinical Trial Data Reported for Insulin Degludec, an Investigational Ultra-Long-Acting Basal Insulin Analog
Current insulin therapy is not a perfect replacement for endogenous insulin. Recent research is directed toward resolving the lack of predictability of insulin action within and between individuals, maintaining long-lasting peakless action in basal insulins, and increasing the speed of rapid-acting insulins. A total of 7 oral abstracts presented at the American Diabetes Association 70th Annual Scientific Sessions on June 25, 2010 featured data from clinical trials of these new insulins. This report summarizes oral abstracts presented on insulin degludec, a new ultra-long-acting basal insulin analog.
The structure and pharmacokinetic (PK) profile of degludec was presented by Peter Kurtzhals (Abstract 0039-OR). Degludec is a hexamer insulin which self-assembles into soluble, multihexamer depot form following subcutaneous injection. PK studies show that degludec is an ultralong acting insulin in all patients, with a minimally variable, peakless time-action profile exceeding 24 hours; it remains detectable in the circulation for 4 days. Potential advantages of this new insulin include less-frequent dosing (possibly less often than once a day) and less daily glycemic fluctuation (which may result in acute hypo- and hyperglycemia, and has been implicated in the development of complications from diabetes).
Bernard Zinman presented phase 2 clinical trial results comparing once-daily or 3-times-weekly degludec with once-daily glargine in 184 patients with type 2 diabetes (Abstract 0040-OR). In this study, background metformin therapy was instituted in all patients; all other oral antidiabetic drugs were discontinued. After 16 weeks of treatment, the efficacy, insulin dose, and hypoglycemia rates were equivalent between all groups. Change in A1C was –1.3%, –1.5%, and –1.5% for degludec once-daily, degludec 3-times-weekly, and glargine once-daily, respectively (baseline A1C = 8.7%). Mean insulin doses were 0.45 IU/kg/d, 0.49 IU/kg/d, and 0.48 IU/kg/d for degludec once-daily, degludec 3-times-weekly, and glargine once-daily, respectively. Rates of confirmed hypoglycemia (plasma glucose < 56 mg/dL or requiring assistance) were 0.6, 2.3, and 1.1 events/patient year for degludec once-daily, degludec 3-times-weekly, and glargine once-daily, respectively. Of note, the number of patients able to achieve A1C < 7% without hypoglycemia was numerically greater in the degludec once-daily group (92%) than in the degludec 3-times-weekly group (77%) or the glargine once-daily group (77%). Dr Zinman noted that further evaluation of 3-times-weekly degludec administration is needed, both with regard to the Monday, Wednesday, Friday schedule followed in the trial, and with regard to the rate of dose titration.
Degludec can be coformulated with insulin aspart, a rapid-acting insulin analog. Relative to biphasic insulin aspart, degludec combined with aspart has a sharper, shorter-lasting peak, followed by a flatter time-action profile, and a more physiological pattern than that of biphasic aspart. Tim Heise presented the results of a phase 2 study comparing once-daily combination degludec (70%)-aspart (30%) with once-daily glargine in 119 insulin-naïve patients with type 2 diabetes (Abstract 0034-OR). After 16 weeks of treatment, equivalent efficacy was attained in both groups; insulin doses and hypoglycemia were both lower in the combined degludec-aspart group. Change in A1C was –1.31% and –1.29% for coformulated degludec-aspart and glargine, respectively (baseline A1C = 8.5%). Mean insulin doses were 0.38 IU/kg/d and 0.45 IU/kg/d for the degludec-aspart combination and glargine, respectively. Rates of confirmed hypoglycemia using the same criteria presented by Zinman and colleagues (Abstract 0040-OR) were 1.2 and 0.7 events/patient year for coformulated degludec-aspart and glargine, respectively. The number of patients able to attain A1C < 7% without hypoglycemia was also equivalent between groups, 51% and 50% for the degludec-aspart combination and glargine, respectively. Dr Heise concludes that coformulated degludec-aspart offers better postdinner glycemic control at lower insulin doses than glargine.
According to the Wall Street Journal, an insulin degludec product launch is anticipated in 2013 (http://online.wsj.com/article/BT-CO-20100625-712480.html).