SLIDE 24 10
Mechanism of action (1) Mechanism of action (2)
Clinical implications- degludec
Insulin degludec 100 units/mL has an ultra-long, flat glucose-lowering PD profile,
with minimal peak-trough variations in effect, and is associated with a reduced risk
- f nocturnal hypoglycemia compared with Gla-100.
Insulin degludec 100 units/mL has a more predictable antiglycemic effect than Gla-
100 in patients with T1D, with a four-fold lower intra-patient variability in glucose lowering action.
The lower intra-patient variability of response to insulin degludec 100 units/mL
compared with Gla-100 was also consistent over the 24-hour dose interval.
Insulin degludec 200 units/mL was compared with Gla-100 in insulin-naïve T2D
patients; a similar reduction in A1C was achieved with both insulins, but insulin degludec 200 units/mL was associated with a greater reduction in fasting plasma glucose (FPG) levels at significantly lower insulin doses.
No significant differences in the rates of overall and nocturnal confirmed
hypoglycemia were observed. There have been no comparison between insulin degludec (100 units/ml or 200 units/ml) with Gla-300.
Clinical experience and long-term safety data for insulin degludec 100 and 200
units/mL are still limited, although no safety concerns regarding unexpected adverse events or accumulation of insulin have been identified to date.
New data- Switch 1 and 2 (unpublished- press release) Heller et al., 2012, Mathieu et al., 2013, Zinman et al., 2012; Garber et al., 2012, Heise et al., 2012, Gough et al., 2013, Rosenstock et al., 2008, Goldman-Levine JD, Patel D, Schnee D. I nsulin de glude c : A no ve l insulin analo gue . Ann Pharmacother. 2013;47(2):269-277
Switch 1 Type 1 DM (Novo- Press Release)
Randomized, double-blind, cross-over, treat-to-target trials, comparing
the safety and efficacy of insulin degludec and insulin glargine U100
The overall purpose of the trial was to compare the hypoglycemia
- ccurrence in people with type 1 diabetes
Primary end-point of the trial was the number of treatment emergent
severe or blood glucose confirmed symptomatic hypoglycemia episodes during the maintenance period (ie after 16 weeks of treatment) in each treatment period.
The trial showed non-inferiority in A1c reduction Non-inferiority was demonstrated in the rate of severe or blood
glucose confirmed symptomatic hypoglycemia of insulin degludec compared to insulin glargine- statistic ally signific ant r
e duc tion of 11%
Non-inferiority was demonstrated for the rate of severe or blood
glucose confirmed symptomatic nocturnal hypoglycemia -statistic ally
signific ant 36% reduction with insulin degludec compared to insulin
glargine.
Superiority was demonstrated for the confirmatory secondary
endpoint of proportions of subjects experiencing severe hypoglycemia during the maintenance period- statistic ally signific ant 35% r
e duc tion.
Switch 2 Type 2 DM (Novo- Press Release)
Randomized, double-blind, cross-over, treat-to-target trials, comparing the
safety and efficacy of insulin degludec and insulin glargine
The overall purpose of the trial was to compare the hypoglycemia
The primary end-point - was the number of treatment emergent severe or
blood glucose confirmed symptomatic hypoglycemia episodes during the maintenance period (ie after 16 weeks of treatment) in each treatment period.
Non-inferiority in A1c reduction was shown between the insulins Rate of severe or BG confirmed symptomatic hypoglycemia during the
maintenance period- statistic ally signific ant r
e duc tion of 30% with insulin
degludec compared to insulin glargine
Severe or blood glucose symptomatic nocturnal confirmed hypoglycemia
in the maintenance period – statistic al signific ant r
e duc tion of 42%
The secondary endpoint of proportions of subjects experiencing severe
hypoglycemia during the maintenance period did not reach statistical significance.
The supportive end-point, rate of severe hypoglycemia, showe d a 46%
r e duc tion with insulin degludec in the maintenance period and a statistic al signific ant r e duc tion of 51% in the full treatment period.
Objective 3
Implement strategies for safely converting between U100 and concentrated insulin formulations in patients with T2DM
