Insulin degludec is a new ultra-long acting basal insulin that has the potential to provide several advantages over existing basal insulins. It has a longer duration of action, allowing for once-daily dosing and flexible administration times. Insulin degludec also has a flat and stable time-action profile and lower day-to-day variability, enabling more predictable control of fasting plasma glucose levels without increasing the risk of hypoglycemia. Pharmacokinetic studies show insulin degludec reaches steady state levels within 3 days of initiation and its effects are not impacted by factors like age, renal impairment, or hepatic impairment. Clinical trials demonstrate insulin degludec is associated with significantly lower rates of overall

1. The Emerging ultra-long acting
basal insulin
Insulin Degludec
Ibrahim El Ebrashy
Prof. Internal Medicine
Head of the Diabetes & Endocrinology Center
Faculty Of Medicine-Cairo University
.

12. • Control fasting BG with one
injection per day for all individuals
• Flexible dosing time
Longer
duration
of action
Lower risk of hypoglycaemia
Flat
time-action
profile
Potential for titration to lower
FPG target without hypoglycaemia
(More predictable action)
Less
day-to-day
variability
Objectives of developing a new basal insulin
BG, blood glucose; FPG, fasting plasma glucose

15. MOP video

18. Half-life of insulin degludec is double that of
insulin glargine
*Insulin glargine was undectable after 48 hours
Results from 66 patients with type 1 diabetes (T1D)
IDeg, insulin degludec; IGlar, insulin glargine
Heise et al. Diabetes 2011;60(Suppl. 1):LB11; Heise et al. Diabetologia 2011;54(Suppl. 1):S425
Insulin degludec Insulin glargine
0.4 U/kg 0.6 U/kg 0.8 U/kg 0.4 U/kg 0.6 U/kg 0.8 U/kg
Half-life (hours) 25.9 27.0 23.6 11.5 12.9 11.9
Mean half-life 25.4 12.1

19. Mean and individual blood glucose profiles
during 42-hour clamp in T1D
Kurtzhals et al. Diabetologia 2011;54(Suppl. 1):S426; Diabetes 2011;60(Suppl. 1A):LB12
Figure shows mean and individual blood glucose profiles following once-daily s.c. dosing of IDeg (0.6 U/kg) for 8 days
Individual patient profile
Mean profile
Time since injection (hours)
Bloodglucoselevel
(mmol/L)

20. Flat time-action profile of insulin Degludec
0
1
2
3
0 4 8 12 16 20 24
GIR(mg/kg/min)
Time (hours)
AUCGIR,0–12h AUCGIR,12–24h
AUCGIR,0–6h AUCGIR,6–12h AUCGIR,12–18h AUCGIR,18–24h
AUCx–y, area under the curve for a specified time interval after injection
GIR, glucose infusion rate
Type 2 diabetes, 49 patients, randomised, 2-period, 12-day trial
Variability was assessed at steady state by clamps on days 6 and 12

21. Insulin Degludec has 4 times lower variability
than insulin Glargine
0
20
40
60
80
100
120
140
160
180
200
220 IDeg
IGlar
Area under the GIR curve (time interval, hours)
Day-to-dayvariability
(coefficientofvariation%)
Endpoint IDeg CV (%) IGlar CV (%) p value
AUCGIR,0-24h 20 82 p<0.0001
Heise et al. Diabetes Obes Metab 2012;14:859-64; 54 patients with type 1 diabetes

24. Flexible and convenient
dosing

25. Steady state in a biological system
Insulin with a T½ of ~ 24 h
Input
Output
Depot
Injected s.c.
In s.c.
Eliminated
(at receptors)
5U
10U
10UDay 1:
Clinical
Steady
State
10U
Day 2: 15U
~9U
10U
Day 3: 17.5U
~10U
10U
Day 4: 19U
10U
10U
Day 5: 20U
7.5U

26. Insulin degludec concentration reaches
steady state in 3 days
54320 1 6
Days since first dose
SerumIDegconcentration
ProportionofDay6level(%)
120
110
100
90
80
70
60
50
40
30
20
10
0
Type 2 diabetes
0 1 2 3 4
SerumIDegconcentration
ProportionofDay4level(%)
120
110
100
90
80
70
60
50
40
30
20
10
0
Days since first dose
Type 1 diabetes
Type 1 diabetes trial, n=66; Type 2 diabetes trial, n=49
T1D trial, 0.4, 0.6 or 0.8 U/kg; T2D trial, 0.4, 0.6 or 0.8 U/ kg
Estimated ratios and 95% CI
Heise et al. Diabetes 2012;61(Suppl. 1):A259

27. Pharmacokinetics of insulin degludec in
special populations Age
Hepatic function
Renal function
Geriatric (≥65)
Younger adults (18–35)
The PK properties of insulin
degludec are not affected by
increasing age, renal impairment
or hepatic impairment
0
2000
4000
6000
8000
10000
0 4 8 12 16 20 24
Insulindegludec
concentration(pmol/L)
Time since injection (hours)
Normal
Mild
Moderate
Severe
0
2000
4000
6000
8000
10000
0 4 8 12 16 20 24
Insulindegludec
concentration(pmol/L)
Time since injection (hours)
Normal
Child-Pugh A
Child-Pugh B
Child-Pugh C
0 4 8 12 16 20 24
Time since injection (hours)
2000
4000
6000
8000
10000
Insulindegludec
concentration(pmol/L)
0
PK, pharmacokinetic
Kupčová et al. Clin Drug Investig 2014;34:127–33; Kiss et al. Clin Pharmacokinet 2014;53:175–83; Korsatko et al. Drugs Aging 2014;31:47–53

28. Hypoglycaemia

40. Summary

42. Insulin degludec:
•Shows significantly lower rates of both overall
and nocturnal confirmed hypoglycaemia in T2D
•Lower hypoglycaemia rates are especially evident in
insulin-naïve patients with T2D based on meta-
analysis results
•Allows for flexibility in the timing of insulin
administration when needed, without compromising
glycaemic control or hypoglycaemia

45. Thank You