Insulin TherapyIn The Treatment Of T2DM

Prof.

Ibrahim El-EbrashyCairo University

Head Of Diabetes & Endocrinology Center

T2DM is insulin resistance + insulin deficiency

Type 2 diabetes

– Characterised by insulin resistance and insulin deficiency

– Degrees of resistance and deficiency vary but insulin deficiency is key to developing diabetes

Adapted from Bergenstal et al. In: Degroot & Jameson (eds). Endocrinology 2001;821–35

Slide No 3

Natural history: insulin secretion and blood glucose control

IFG, impaired fasting glucose

35030025020015010050

Postprandial glucose

Fasting glucose

Obesity IFG Diabetes Uncontrolled hyperglycaemia

250200

15010050

Insulin resistance

Insulin level

Years of diabetes

–10 2520151050–5 30

Beta-cell failure

Glu

cose level

(mg

/dL)

Rela

tive

fun

cti

on

(%

)

Normal

Normal

Adapted from Bergenstal et al. In: Degroot & Jameson (eds). Endocrinology 2001;821–35

Improving control reduces risks of long-term complications

• Every 1% drop in HbA1c can reduce long-term diabetes complications

43%

Lower extremity amputation or fatal peripheral

vascular disease

37%

Microvascular disease

19%

Cataract extraction

14%

Myocardial infarction

16%

Heart failure

12%

Stroke

UKPDS 35: Stratton et al. BMJ 2000;321:405–12

Slide no 4

Positive legacy effect of early, intensive glucose control

RRR = Relative Risk Reduction

Red indicates significant reduction on intensive therapy vs. conventional therapy

At end of post-trial follow up (median 8.5 years)

Aggregate endpoint 1997 2007

Any diabetes-related endpoint

RRR: 12% 9%

Microvascular disease RRR: 25% 24%

Myocardial infarction RRR: 16% 15%

All-cause mortality RRR: 6% 13%

UKPDS 80. Holman et al. N Engl J Med 2008; 359:1577-89

Slide no 5

Insulin is the most effective anti-diabetic agent

Nathan DM. N Engl J Med. 2007;356:437-40

Slide no 6

1.5 1.5 1.0-1.5 0.5-0.9 0.8-1.0

≥2.5

SulfonylureasBiguanides(metformin) Glinides

DPP-IVinhibitors TZDs Insulin

0.0

0.5

1.0

1.5

2.0

2.5

3.0

HbA

1c re

duct

ion (

%)

Efficacy as mono

therapy

Anti diabetic agents

Insulin use is often delayed, despite poor glycaemic control

Slide no 7

1 OAD

2 OADs

3 OADs

Diet

2.9 years 4.7 years 2.5 years 2.7 years

8

9

10

8.8%

9.4% 9.1%

OAD, oral antidiabetic drug

Mean H

bA

1c a

t la

st

vis

it (%

)

Novo Nordisk. Type 2 Diabetes Market Research Roper Starch US Study, 2000

T2DM treatment patterns in Egypt2010-14, thousand patients

Slide no 9

2010-12Change

16%

11%

11%

3%

16%

100%

There is resistance to insulin despite efficacy and guideline recommendations

In a survey of insulin-naïve T2DM patients, 28.2% of respondents reported that they would be unwilling to take

insulin if it were prescribed3

UKPDS• 27% of T2DM patients randomized to insulin

initially refused treatment1

DAWN• More than half of insulin-naïve T2DM patients

expressed anxiety about starting insulin therapy2

1UKPDS 33, 1998; 2Peyrot et al. 2005; 3Polonsky et al. 2005Kunt and Snoek Int J Clin Pract 2009; 63:6-10

Slide no 10

Barriers to starting insulin• Fear of hypoglycaemia

• Fear of reduced quality of life

• Reluctance to inject in public

• Perception that the disease is becoming more severe

• Fear of needles/pain from injections

• Patients do not feel empowered to take control of their diabetes

Korytkowski . Int J Obes Relat Metab Disord 2002;26:S18–S24Polonsky et al. Diabetes Care 2005;28(10):2543-2545

Rubin and Peyrot. J Clin Psychol 2001;57:457– 478

Slide no 11

Clinical inertia: delay in treatment initiation and optimisation

TherapyTherapyN=66726N=66726

Diabetes durationDiabetes duration(years)(years)

Mean (SD)Mean (SD)

HbAHbA1c 1c

(%)(%)Mean (SD)Mean (SD)

No therapy

(9%)2.1 (8.6) 10.0 (2.2)

OGLD only

(58%)8.3 (6.3) 9.5 (1.7)

Insulin +/- OGLD

(33%)12.0 (7.7) 9.4 (1.8)

Home et al. Diabetes Res Clin Pract 2011; 94: 352-63

Slide no 13

Often there is a failure to advance therapy even when required

Time to insulin initiation in patients on >1 OAD is 7.7 yrs†

Perc

enta

ge P

ati

ents

(%

)

Delay in insulin initiation (years)

†95% CI = 7.4 to 8.5 years

Calvert et al. Br J Gen Pract 2007;57:455-460

Slide no 14

Common reasons for clinical inertia

Insulin makes one fat

Fear ofhypos

Pain frominjection

Pain fromblood tests

Insulin makes one fat

Fear ofhypos

Pain frominjection

Pain fromblood tests

* Percentage of patients/physicians interviewed who provided this as a reason for not starting insulin

Insulin naïve patients Primary care physicians

Nakar et al. J Diabetes Complications 2007;21:220–6

Slide no 15

Patient concerns still exist after insulin initiation

0

10

20

30

40

50

60

70

80

Diabeteshas

progressed

Lessflexibility

Injectionfear

Weightgain

Seen as sick

p<0.001 for all

Perc

en

tag

e o

f su

bje

cts

wh

o a

gre

eor

str

on

gly

ag

ree

Insulin naïve

Insulin-treated

Increased risk ofhypoglycaemia

Snoek et al. Health and Quality of Life Outcomes 2007;5:69

Slide no 16

Sequential Insulin Strategies in T2DM Diabetes Care, Diabetologia. 19 April 2012 [Epub ahead of print]

Algorithm for initiating insulin therapy.

Patient-Based Insulin Regimens

Starting Dosages Start Low and Titrate Steadily

Dosage Titration for Once-Daily or Twice-Daily Insulin Regimens

                                                                 

Transition From One Regimen to Another

Data about Premixed Insulin Aspart in treatment of Diabetes

Nazia Raja-Khan, Sarah S Warehime, and Robert A Gabbay

Vasc Health Risk Manag. 2007 December; 3(6): 919–935.

Percentage of subjects achieving HbA1c target values at the end of the study.

Raskin P et al. Dia Care 2005;28:260-265

Copyright © 2011 American Diabetes Association, Inc.

Eight-point SMPG readings before breakfast, lunch, and supper [BB, BL, and BD] and 90 min after breakfast, lunch, and supper [B90, L90, and D90]; at bedtime [Bed]; and at 3:00 a.m.).

Raskin P et al. Dia Care 2005;28:260-265

Copyright © 2011 American Diabetes Association, Inc.

Case 1

q A 49-years-old male patient with T2DM 8 years ago, being treated with Insulin Glargine 20 unites at 11 pm and glimpride 3mg before breakfast and metformin 2g/day since 2 years

BMI 30

qLifestyle:

High-carbohydrate meals is fond of rice or bread and potatoes.

Does not exercise.

•HbA1c = 7.5%

•On antihypertensive for several years.

•Recently, a statin has been added to his

medications

He wants to fast in ramadan?

Yes

No

• What due think you should first ask before deciding the his treatment regimen in ramadan ?

1. His blood glucose analysis during the day

• Blood glucose levels over the day:

FBG 145mg/dl

PPG (Post-breakfast) 165 mg/dl

Pre Lunch 133 mg/dl

PPG (Post-Lunch) 167 mg/dl

Pre Dinner 166 mg/dl

After Dinner ( main meal ) 261 mg/dl

What are the option to control his blood glucose ?

• Increase the dose of glargine?

• Add a mealtime bolus?

• Shift to basal-bolus insulin regimen?

• Switched to premixed analogue insulin before eftar and SU at a lower dose before sohoor and the same metformin doses?

• What dietary advice you have to give him in Ramadan ?

1. Eftar starting with a lot of fluids and no sugar

2. Snack after praying taraweeh

3. Lot of fluid during the time allowed to eat

4. Late sohoor

Thank You