Transcript Slide 1

Insulin Therapy
In The Treatment Of T2DM
Prof.
Ibrahim El-Ebrashy
Cairo 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
Glucose level
Relative
(mg/dL)
function (%)
Obesity IFG
250
200
150
100
50
Diabetes
Uncontrolled hyperglycaemia
Insulin resistance
Insulin level
Beta-cell failure
350
300
250
200
150
100
50
Normal
Postprandial glucose
Fasting glucose
Normal
–10
–5
0
5
10
15
20
25
30
Years of diabetes
IFG, impaired fasting glucose
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%
37%
19%
16%
14%
12%
Stroke
Heart failure
Cataract
extraction
Microvascular
disease
Lower extremity
amputation or fatal
peripheral vascular
disease
UKPDS 35: Stratton et al. BMJ 2000;321:405–12
Myocardial
infarction
Slide no 4
Slide no 5
Positive legacy effect of early,
intensive glucose control
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%
At end of post-trial follow up (median 8.5 years)
RRR = Relative Risk Reduction
Red indicates significant reduction on intensive therapy vs.
conventional therapy
UKPDS 80. Holman et al. N Engl J Med 2008; 359:1577-89
Slide no 6
Insulin is the most effective
anti-diabetic agent
Sulfonylureas
Biguanides
(metformin)
1.5
1.5
Glinides
DPP-IV
inhibitors
TZDs
1.0-1.5
0.5-0.9
0.8-1.0
Insulin
HbA1c reduction (%)
0.0
0.5
1.0
≥2.5
1.5
2.0
2.5
3.0
Efficacy as
mono
therapy
Nathan DM. N Engl J Med. 2007;356:437-40
Anti
diabetic
agents
Slide no 7
Mean HbA1c at last
visit (%)
Insulin use is often delayed,
despite poor glycaemic control
10
9.4%
9.1%
8.8%
9
8
3 OADs
2 OADs
1 OAD
Diet
2.9 years
4.7 years
2.5 years
OAD, oral antidiabetic drug
Novo Nordisk. Type 2 Diabetes Market Research
Roper Starch US Study, 2000
2.7 years
Slide no 9
T2DM treatment patterns in Egypt
2010-14, thousand patients
2010-12
Change
100%
16%
16%
11%
11%
3%
Slide no 10
There is resistance to insulin despite
efficacy and guideline recommendations
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
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
1UKPDS
33, 1998; 2Peyrot et al. 2005; 3Polonsky et al. 2005
Kunt and Snoek Int J Clin Pract 2009; 63:6-10
Slide no 11
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–S24
Polonsky et al. Diabetes Care 2005;28(10):2543-2545
Rubin and Peyrot. J Clin Psychol 2001;57:457– 478
Slide no 13
Clinical inertia: delay in treatment
initiation and optimisation
Diabetes duration
(years)
HbA1c
(%)
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)
Therapy
N=66726
Home et al. Diabetes Res Clin Pract 2011; 94: 352-63
Slide no 14
Often there is a failure to advance
therapy even when required
100
Percentage Patients (%)
90
Time to insulin initiation in
patients on >1 OAD is 7.7 yrs†
80
70
60
50
40
30
20
10
†95% CI = 7.4 to 8.5 years
0
0
1
2
3
4
5
6
7
8
9
10
Delay in insulin initiation (years)
Calvert et al. Br J Gen Pract 2007;57:455-460
Slide no 15
Common reasons for clinical inertia
Insulin naïve patients
Insulin
makes
one fat
Fear of
hypos
Pain from
injection
Pain from
blood
tests
Primary care physicians
Insulin
makes
one fat
Fear of
hypos
Pain from
injection
* Percentage of patients/physicians interviewed who provided this as a
reason for not starting insulin
Nakar et al. J Diabetes Complications 2007;21:220–6
Pain from
blood
tests
Patient concerns still exist after
insulin initiation
Slide no 16
Percentage of subjects who agree
or strongly agree
Insulin naïve
Insulin-treated
80
p<0.001 for all
70
60
50
40
30
20
10
0
Diabetes
has
progressed
Less
flexibility
Injection
fear
Weight
gain
Seen
as sick
Snoek et al. Health and Quality of Life Outcomes 2007;5:69
Increased risk of
hypoglycaemia
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