1. Say Yes to Insulin
Mentorship Program
Initiating insulin
Kick-off meeting
林文玉醫師
金磚 20120827

2. Insulin use was
inadequately
delayed

3. Before Starting Insulin, Patients Spend an Estimated 10 Years
Above Target
10 35 Months*
27 Months*
9.1 Metformin
9 8.8 monotherapy
Sulfonylurea
8.2 monotherapy
8 7.6 7.7
A1C %
7.1
7 ADA goal
6
05
First HbA1c on Best HbA1c on Last HbA1c before
treatment treatment switch or addition
Modified: Monotherapy switched to another agent or additional agent added.
*Mean number of months until a new or additional treatment was started
Adapted from Brown JB, et al. Diabetes Care 2004;27:1535–40

4. Progressively declining beta cell function in T2D
‘waiting for failure’
Insulin ±oral drugs
Dual for lowering
100 Lifestyle Monotherapy therapy blood glucose
10
ß-cell function (%)
9
8
HbA1c (%)
7
6
HbA1c
5
ß-cell function
0 0
0 Time >15
(years)
Adapted from: Heine RJ et al. BMJ. 2006;333:1200-1204.

5. The impact of glycemic control on complications
The majority of people with type 2 diabetes fail to reach
recommended goals for glycemic control1
Intensive glucose control is associated with long-term reductions in
long-term diabetes complications—the legacy effect
17% 15% 15% 13% 9%
p=0.01 p=0.01 p=0.01 p=0.007 p=0.04
Diabetes Myocardial Microvascular Death Any diabetes
death infarction disease (any cause) endpoint
1. Del Prato, et al. Int J Clin Pract Suppl 2007;157:47-57
2. Holman et al, NEJM 2008;359:1577-1589

6. No HbA1C Threshold in Type 2 Diabetes
80
Myocardial infarction Epidemiologic
Adjusted Microvascular endpoints Data from the
incidence per UKPDS
60
1000 person
years (%) ADA Goal
40
20
?
0
5 6 7 8 9 10 11
Updated mean HbA1C (%)
Stratton IM, et al. BMJ. 2000;321:405-412.
6

7. June 2012 vol. 7, issue 6

10. “Clinical Inertia”
Failure to advance therapy when required
Last HbA1C Value Before Abandoning Treatment
10
9.6%
9.1%
9
8.8%
8.6%
8
% Mean HbA1C at
ADA Goal
last visit1
7
Sulfonylurea
Diet/Exercise Combination
Metformin
2.5 years 2.9 Years 2.2 Years 2.8 Years
1Brown et al. The Burden of Treatment Failure in Type 2 Diabetes. Diabetes Care 27: 1535-1540, 2004 10

11. Clinical Inertia: “Failure to advance therapy when required”
Percentage of Subjects advancing when HbA1C > 8%
At Insulin Initiation, the average patient had:
100 • 5 years with HbA1C > 8%
• 10 years with HbA1C > 7%
80
%Age of Subjects
66.6%
60 44.6%
35.3%
40
18.6%
20
0
Diet Sulfonylurea Metformin Combination
Brown et al. The Burden of Treatment Failure in Type 2 Diabetes.
Diabetes Care 27: 1535-1540, 2004 11

12. Clinical Inertia: “Failure to advance therapy when required”
4207 Person-Years of Followup
At Insulin Initiation, patients who had failed
combination therapy
• Had a median HbA1C of 9.9%
“The high median HbA1C that preceded the initiation of insulin in our population
is particularly troubling and suggests that there are substantial barriers to its
Initiation”
Cook et al: Glycemic Control continues to deteriorate after Sulfonylureas Are Added
to Metformin Among Patients with Type 2 Diabetes. Diabetes Care 28: 995-1000, 2005
12

13. Treatment Algorithm for Type 2
Diabetes in Adults*
Education/Nutrition/Exercise
Goals met FPG/SMBG goals not met after 1 month
Follow-up Every 3 Start Initial Oral Monotherapy
to 6 Months or Early Dual Oral Therapy
Therapy adequate Goals not met after 3 months
Continue Therapy Initiate/Modify Dual
HbA1c Every 3 to 6 Months Therapy
Therapy adequate Goals not met after 3 to 6 months
Continue Dual Therapy Add Evening Insulin or Third Oral Agent;
HbA1c Every 3 to 6 Months Consider Referral to Endocrinologist
Goal: FPG/SMBG <6.5 mmol/L; HbA1C <6.5%†
*Modified Texas Diabetes Council Algorithm. Feld S. Endocr Pract. 2002;8(suppl 1):40-82.
†American College of Endocrinology. 13

14. What should I tell people with Type 2
diabetes about insulin?
‘Most people with Type 2 diabetes eventually
need insulin because their own production of
insulin falls off with time and they therefore
inevitably become insulin deficient’
• Diabetes is caused by a progressive failure of insulin production
in people who are usually insulin insensitive (overweight)

15. Progression of Type 2 diabetes relates to
declining islet -cell function while insulin
insensitivity is unchanged
Time to need glucose-lowering
medication
2–4 years
5–7 years
-Cell 60 Insulin 60 8–10 years
function sensitivity
(%)
40 40
20 20
0 0
0 2 4 6 0 2 4 6
Years from diagnosis
Levy J et al. Diabet Med. 1998;15:290-296

16. Progression to Type 2 diabetes usually involves a
failure of insulin secretion in people who are already
insulin insensitive
500
400
(insulin response mU/l)
Insulin secretion
300 Normal – compensated insulin resistance
Normal
Normal
200
IGT
100 Diabetes
0
0 1 2 3 4 5
Insulin sensitivity
(glucose requirement mg/kg/min)
Adapted from Weyer C et al. J Clin Invest. 1999;104:787-794

17. What should I tell people
with Type 2 diabetes about insulin?
‘If you need insulin, it doesn’t mean you failed.
Tablets cannot control blood glucose forever, because
they don’t stop the problem of your own declining
insulin production getting worse’
• Islet -cell dysfunction worsens over time, regardless
of therapy

18. UKPDS: Islet -cell function and the progressive
nature of diabetes
100 Time of diagnosis
80
(% of normal by HOMA)
Islet -cell function
60
40 Pancreatic function
= 50% of normal
20
0
10 9 8 7 6 5 4 3 2 1 0 1 2 3 4 5 6
Years
HOMA = homeostasis model assessment
Holman RR. Diab Res Clin Pract. 1998;40(suppl):S21-S25;
UKPDS. Diabetes. 1995;44:1249-1258

19. What should I tell the person with Type 2
diabetes who needs
insulin, but doesn’t want to take it?
‘Insulin will not make your diabetes worse. In fact,
it will help control your glucose, so you’ll have
fewer complications and you’ll feel better.’
• Strict glycaemic control reduces the risks of both microvascular
and macrovascular complications
• People who start insulin usually feel much better for it

20. How should I start insulin therapy for my
patients with Type 2 diabetes?
• According to the IDF Global Guideline for Type 2
Diabetes
– Insulin is the most effective way of reducing hyperglycaemia
– Insulin can be started as a basal insulin alone or with premix
insulin
– Start insulin when glucose control on maximum tablets >7.5
% (HbA1c)
– Begin at low dose but titrate up rapidly in first month
IDF. Global Guideline for Type 2 Diabetes. 2005

21. Treat-to-Target: addition of detemir or NPH
to oral therapy
475 People with Type 2 Diabetes on 1 or 2 Oral Agents
Glycaemic Control Hypoglycaemia (events pt-yr-1)
Baseline HbA1c 8.5% 8.6%
0.0 12
-0.5
HbA1c
8
-1.0
NPH
-1.5 4
detemir
-2.0 -1.8%
-1.9%
P=NS 0
Final HbA1c 6.6% 6.8% 5.0 6.0 7.0 8.0 9.0
NPH insulin HbA1c (%)
Insulin detemir
Hermansen K et al. Diabetes Care. 2006;29:1269-1274

22. What are the problems associated with
insulin therapy?
• Weight gain is usual as glycosuria is reduced
• Hypoglycaemia will occur in some people – education is
needed
• Failure of dose titration to get adequate glucose control
• Worsening of control as islet β-cell failure progresses
• These risks can be minimized by
– use of insulin analogues in those with problems
– using basal insulin only when starting at lower HbA1c
– appropriate education on eating and physical activity
– active and continuing support for dose titration
– intensification of insulin regimens over following years

23. Conclusions
• Due to declining -cell function, insulin therapy will be necessary
for most patients with Type 2 diabetes
• Insulin effectively lowers HbA1c, thereby reducing the risks of
both micro- and macrovascular complications
• IDF Global Guidelines recommend starting insulin when glucose
control on maximum tablets >7.5 % (HbA1c)
• To maintain target glucose levels in the long-term, many patients
will require intensive insulin therapy (basal + bolus insulin) in
combination with an insulin sensitizer