4. American Diabetes
Association
‘Therefore, the results of the
UKPDS mandate
that treatment of type 2 diabetes
include
aggressive efforts to lower blood
glucose levels
as close to normal as possible’
5. 1 American Diabetes Association. Diabetes Care 2004; 27:S15–S35.
2 American Diabetes Association. Diabetes Care 2002; 25:S35–S49.
3 American Association of Clinical Endocrinologists. Endocrine Pract 2002; 8 (Suppl. 1):40–82.
4 European Diabetes Policy Group. Diabet Med 1999; 16: 716–730.
NA110–150
Bedtime plasma
glucose
< 140< 180
Postprandial
plasma glucose
< 11090–130
Fasting/preprandial
plasma glucose
Biochemical index AACE3
ADA1,2 IDF4
(Europe)
mg/dl mmol/l mg/dl mmol/l mg/dl mmol/l
< 6.05.0–7.2
< 10.0
< 6.5< 7HbA1c (%) < 6.5
< 110< 6.0
NA
NA
6.0–8.3
< 7.8 NA
NANA
ADA, AACE and IDF glycemic
goals
6. 1 Koro CE, et al. Diabetes Care 2004; 27:17–20. 2 Liebl A. Diabetologia 2002; 45:S23–S28.
Majority of type 2 diabetes patients in US
and EU have inadequate glycemic control
Percentageofsubjects
0
20
40
60
80
100
< 7% 7%
HbA1c (%)
US1
36%
64%
Percentageofsubjects
0
20
40
60
80
100
6.5% > 6.5%
HbA1c (%)
EU2
31%
69%
7. What are the barriers to
achieving and sustaining
glycemic goals?
How can these be overcome?
8. What are the barriers to achieving
and sustaining glycemic goal?
1) Ineffective diet and exercise?
2) Poor compliance.
3) Complexity of pathophysiologic mechanisms of
Type 2 Diabetes.
4) Suboptimal health care system.
5) Ineffective pharmacological agents.
9. Barriers to goal
• Ineffective diet/exercise initiatives
• Lack of efficacy of pharmacological agents
• Conservative management
• Adverse events
• Poor compliance
• Underlying pathophysiology
• Sub-optimal healthcare systems
10. Barriers to goal
• Ineffective diet/exercise initiatives
• Lack of efficacy of pharmacological agents
• Conservative management
• Adverse events
• Poor compliance
• Underlying pathophysiology
• Sub-optimal healthcare systems
12. Barriers to goal
• Ineffective diet/exercise initiatives
• Lack of efficacy of pharmacological agents
• Conservative management
• Adverse events
• Poor compliance
• Underlying pathophysiology
• Sub-optimal healthcare systems
13. Conservative management of diabetes?
• It is a considerable barrier to good glycemic
control .
• Unacceptable delays in treatment.
• Maximal monotherapy dose may not an optimal
dose.
• Proactive management of glycemia : early
combination approach.
• Traditional stepwise approach is not a
conservative treatment.
16. *May include uptitration. Length of time between first HbA1c > 8% and switch/addition in therapy could include periods where patients had subsequent HbA1c test
values below 8%. Based on nonrandomized retrospective database analysis. Data from Kaiser Permanente Northwest 1994–2002. Patients had to be
continuously enrolled for 12 months with HbA1c lab values
Unacceptable delays in
treatment
0
5
10
15
20
25
Metformin only Sulfonylurea only
Months
n = 354 n = 2517
14 months
20 months
Length of time between first monotherapy
HbA1c > 8.0%* and switch/addition in therapy*
Adapted from Brown & Nichols. Diabetes 2003; 52 (Suppl 1):A61
17. These are consideration in pharmacologic
treatment of Type 2 diabetes.
• Maximum dose of one pharmacological agent.
• Effective HbA1c lowering capacity.
• Mechanisms of action of drugs.
• Impact on weight gain.
• Frequency of hypoglycemia.
18. Maximal monotherapy dose may
not be optimal dose
Adapted from Garber AJ et al. Am J Med 1997; 103:491–497
*
Fasting Plasma Glucose
*P = 0.054; **P<0.01; ***P<0.001 for estimated difference from placebo.
DifferencefromPlacebo(mg/dL)
-100
-80
-60
-40
-20
0
500 1000 1500 2000 2500
HbA1c
***
***
***
**
-2.5
-2
-1.5
-1
-0.5
500 1000 1500 2000 2500
***
***
***
***
***
Metformin Dosage (mg)
DifferencefromPlacebo%
0
19. UKPDS 28. Early addition of metformin
in Su treated Type 2 diabetic patients*.
-10
-8
-6
-4
-2
0
2
4
6
8
10
Sulfonylurea SU+Metformin
5
6
7
8
9
Sulfonylurea SU+Metformin
P<0.00001
P=0.006
UKPDS Group Diabetes Care 1985;21:87
*N= 591; Follow-up= 3 yrs
Change in fasting plasma glucose
(mg/dl)
HbA1c (%)
21. Considerations in Pharmacologic
Treatment of Type 2 Diabetes
• Efficacy (HbA1c lowering capacity)
• Mechanisms of action of drugs
• Impact on weight gain
• Complications/tolerability/contra-
indications
• Frequency of hypoglycemia
• Compliance/complexity of regimen
• Cost
22. These are another barriers for good
glycemic control.
• Reluctance to prescrible new agents.
• Poor compliance.
• Inadequate monitoring of glycemia.
• Complexity of managing hyperglycemia relative to
dyslipidemia and hypertention.
• All of the above.
23. Barriers to goal
• Ineffective diet/exercise initiatives
• Lack of efficacy of pharmacological agents
• Conservative management
• Adverse events
• Poor compliance
• Underlying pathophysiology
• Sub-optimal healthcare systems
24. How to correct the barriers to good
glycemic goal.
• Ineffective diet / exercise initiatives.
26. • How to correct conservative
treatment?
• How to correct adverse events of
drugs.
• How to improve poor compliance of
patient.
• How can we organize the
suboptimal health care systems.
28. Reluctance to prescribe new
agents
Nesto RW, et al. Circulation 2003; 108:2941–2948
Nesto RW, et al. Diabetes Care 2004 27:256–263
29. Ranking of barriers to achieving glycaemic
targets
(1=Most important / 3=Least important)
• Poor patient compliance
• Lack of long-term efficacy of
agents
• Side effects of higher doses
Most important
58%
28%
14%
n=98
30. Barriers to goal
• Ineffective diet/exercise initiatives
• Lack of efficacy of pharmacological agents
• Conservative management
• Adverse events
• Poor compliance
• Underlying pathophysiology
• Sub-optimal healthcare systems
31. Percent of health professionals knowing
correct answers to questions about OHA
0
10
20
30
40
50
60
70
80
90
100
Percent
Total Nurses Pharmacists Doctors
Drug timing
Mechanism
Side effects
Browne DL et al; Diab Med 2000; 17:528
32. Barriers to goal
• Ineffective diet/exercise initiatives
• Lack of efficacy of pharmacological agents
• Conservative management
• Adverse events
• Poor compliance
• Underlying pathophysiology
• Sub-optimal healthcare systems
33. Barriers to goal
• Ineffective diet/exercise initiatives
• Lack of efficacy of pharmacological agents
• Conservative management
• Adverse events
• Poor compliance
• Underlying pathophysiology
• Sub-optimal healthcare systems
34. Barriers to goal
• Ineffective diet/exercise initiatives
• Lack of efficacy of pharmacological agents
• Conservative management
• Adverse events
• Poor compliance
• Sub-optimal healthcare systems
• Underlying pathophysiology
35. Barriers to goal
• Intensify population programs
• Lack of efficacy of pharmacologic agents
• Conservative management
• Adverse events
• Poor compliance
• Sub-optimal healthcare systems
• Underlying pathophysiology
36. Barriers to goal
• Intensify population programs
• Optimize their use, combine them
• Conservative management
• Adverse events
• Poor compliance
• Sub-optimal healthcare systems
• Underlying pathophysiology
37. Barriers to goal
• Intensify population programs
• Optimize their use, combine them
• Adopt an uncompromising insistence on
“treating to target”
• Adverse events
• Poor compliance
• Sub-optimal healthcare systems
• Underlying pathophysiology
38. Barriers to goal
• Intensify population programs
• Optimize their use, combine them
• Adopt an uncompromising insistence on
“treating to target”
• Blame yourself before blaming the patient
• Poor compliance
• Sub-optimal healthcare systems
• Underlying pathophysiology
39. Barriers to goal
• Intensify population programs
• Optimize their use, combine them
• Adopt an uncompromising insistence on
“treating to target”
• Blame yourself before blaming the patient
• Don’t prescribe, share therapeutic decision
• Sub-optimal healthcare systems
• Underlying pathophysiology
40. Barriers to goal
• Intensify population programs
• Optimize their use, combine them
• Adopt an uncompromising insistence on
“treating to target”
• Blame yourself before blaming the patient
• Don’t prescribe, share therapeutic decision
• Don’t miss good chances
• Underlying pathophysiology
41. Barriers to goal
• Intensify population programs
• Optimize their use, combine them
• Adopt an uncompromising insistence on
“treating to target”
• Blame yourself before blaming the patient
• Don’t prescribe, share therapeutic decision
• Don’t miss good chances
• We are the specialists!
42. What are the barriers to insulin therapy?
• Fear of injection?
• Insulin therapy linked to poor prognosis.
• Insulin leads to weight gain.
• Hypoglycemia.
• Insulin is atherogenic.
• Insulin leads to improving insulin sensitivity.
43. Patient Barriers to Insulin Therapy
• Fear of injections
Reality: With new needles, injections are
well tolerated
• Insulin therapy linked to poor prognosis
Reality: No actual link – poor prognosis
because insulin is begun very late in
disease progression
• Insulin leads to weight gain
Reality: Weight gain is modest and can
be minimized by regulating caloric intake
and increasing physical activity
44. Provider Barriers to Insulin Therapy
• Hypoglycemia
Reality: Rare in patients with type 2 and
manageable in patients with type 1 by diet and
insulin adjustment
• Insulin is atherogenic
Reality: Data do not support this concern -
poorly controlled patients have increased CVD
• Worsening insulin resistance
Reality: Insulin improves insulin sensitivity by
reducing glucotoxicity
45. Health care system barrier to insulin
therapy
• Office can not easily be setup to manage patient
on insulin.
• No diabetes team in office.
• All of the above.
• None of the above.
46. Health Care System
Barriers to Insulin Therapy
• Offices can not easily be set up to
manage patients on insulin
Reality: Existing systems can easily
be modified to manage these
patients
• No diabetes team in office
Reality: “Team” can be community
resources
47. Canadian and American
Diabetes Associations
‘Diabetes must be prevented
sooner, and diagnosed earlier.
Canadian Diabetes Association, 2003.
American Diabetes Association. Diabetes Care 2003; 26:S28–S32.
And once diagnosed, all types of
diabetes must then be managed
much more aggressively’
48. Barriers to Sulfonylurea
• Weight gain.
• Hypoglycemia.
• Exaggerated pancreatic β-cell failure.
• Possible cardiotoxicity.
53. Cardiomyocytes have KATP channels in two
sites:
a) In sacrolemmal membrane.
b) In mitochondrial membrane.
Sulfonylureas differ in their relative
affinities for sacrolemmal and mitochondrial
KATP channels.
55. Glimepiride:
Glimepiride has powerful affinity
both the pancreatic SUR1/Kire 6.2 and
myocardial SUR2/Kir6.2 similar to that of
Gb (Song and Aschroft, Br. J pharmacol, 2001,
133-139).
56. However, the effects of this substance on
the myocardium in animals as compared with
Gb, seem to be far more modest. Several in
vitro and in vivo studies have failed to find
any effect of glimepiride on IPC.
57. IPC was modeled in the cardiac
catheterization by repeated inflation of an
angioplasty balloon.
In patients receiving a placebo infusion, the
magnitude of ST-depression decreased
progressively with subsequent balloon inflation
IPC.
58. Following a glimepiride infusion, patients had
similar, progressive decrease in st segment depression
with subsequent balloon inflations, suggesting no
adverse effect of glimepiride on IPC. In contrast,
patients pretreated with glyburide had no change in the
magnitude of st segment depression with subsequent
balloon inflations (Klepzig et al., 1999. Eur Heart H 20: 439-
446).
59. BARRIERS TO METFORMIN .
1- G ASTERINTESINAL UPSETS
2-INCREASED INCIDENCE OF LACTIC
ACIDOSIS
3-IT IS THE FIRST DRUG TO BE USED IN ALL
GUIDELINES
4-IN EVIDENCE BASED STUDIES METFORMIN
IS THE ONLY ANTIHYPERGLYCEMIC TO
SHOW IMPROVED MACROVASCULAR
EVENTS
60. • METFORMIN IS COTRAINDICATED IN PATINTS
WITH:
ADAVANCED LIVER DISEASE
DIABETIC NEPHROPATHY WITH GFR LESS
THAN 50 ml/min
GESTIONAL DIABETES
NAFLD
HEART FAILURE
RESPIRATORY FAILURE
