Ueda2016 symposium -the emerging ultra-long acting basal insulin- ibrahim el ibrashy

The Emerging ultra-long acting basal insulin

Insulin Degludec

Ibrahim El EbrashyProf. Internal Medicine

Head of the Diabetes & Endocrinology Center Faculty Of Medicine-Cairo University.

• Control fasting BG with one injection per day for all individuals

• Flexible dosing time

Longer duration of action

Lower risk of hypoglycaemiaFlat 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

MOP video

Half-life of insulin degludec is double that of insulin glargine

*Insulin glargine was undectable after 48 hoursResults from 66 patients with type 1 diabetes (T1D)IDeg, insulin degludec; IGlar, insulin glargineHeise 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

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 profileMean profile

Time since injection (hours)

Blo

od g

lucose level

(mm

ol/

L)

Flat time-action profile of insulin Degludec

0

1

2

3

0 4 8 12 16 20 24

GIR

(m

g/k

g/m

in)

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 injectionGIR, glucose infusion rateType 2 diabetes, 49 patients, randomised, 2-period, 12-day trialVariability was assessed at steady state by clamps on days 6 and 12

Insulin Degludec has 4 times lower variabilitythan insulin Glargine

0

20

40

60

80

100

120

140

160

180

200

220 IDegIGlar

Area under the GIR curve (time interval, hours)

Day-t

o-d

ay v

ariability

(coeffic

ient

of variation %

)

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

Flexible and convenient dosing

Steady state in a biological systemInsulin with a T½ of ~ 24 h

Input

Output

Depot

Injected s.c.

In s.c.

Eliminated(at receptors)

5U

10U10UDay 1:

ClinicalSteadyState

10UDay 2: 15U

~9U

10UDay 3: 17.5U

~10U

10UDay 4: 19U

10U

10UDay 5: 20U

7.5U

Insulin degludec concentration reaches steady state in 3 days

54320 1 6

Days since first dose

Seru

m I

Deg c

oncentr

ation

Pro

port

ion o

f D

ay 6

level (%

)

120

110

100

90

80

70

60

50

40

30

20

10

0

Type 2 diabetes

0 1 2 3 4

Seru

m I

Deg c

oncentr

ation

Pro

port

ion o

f D

ay 4

level (%

)

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=49T1D trial, 0.4, 0.6 or 0.8 U/kg; T2D trial, 0.4, 0.6 or 0.8 U/ kgEstimated ratios and 95% CIHeise et al. Diabetes 2012;61(Suppl. 1):A259

Pharmacokinetics of insulin degludec in special populations Age

Hepatic functionRenal 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

Insulin d

eglu

dec

concentr

ation (

pm

ol/

L)

Time since injection (hours)

Normal

Mild

Moderate

Severe

0

2000

4000

6000

8000

10000

0 4 8 12 16 20 24

Insulin d

eglu

dec

concentr

ation (

pm

ol/

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

Insulin d

eglu

dec

concentr

ation (

pm

ol/

L)

0

PK, pharmacokineticKupčová 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

Hypoglycaemia

Summary

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

Thank You