Canadian Diabetes Association

1
Canadian Diabetes Association 2003 Clinical
Practice Guidelines for the Prevention and
Management of Diabetes in Canada
Getting to Goal in Type 2 Diabetes
2
Proportion of patients with A1C gt 7.0 increases
with duration of type 2 diabetes
lt2
3-5
6-9
10-14
15
Years T2DM
Harris,S et al. CDA 2003 Type 2 Diabetes and
Associated Complications in Primary Care in
Canada The Impact of Duration of Disease on
Morbidity Load.
3
Proportion of patients with hypertension
increases with duration of type 2 diabetes
lt2
3-5
6-9
10-14
15
Years T2DM
Harris,S et al. CDA 2003 Type 2 Diabetes and
Associated Complications in Primary Care in
Canada The Impact of Duration of Disease on
Morbidity Load.
4
Proportion of patients with dyslipidemia
increases with duration of type 2 diabetes
lt2
3-5
6-9
10-14
15
Years T2DM
Harris,S et al. CDA 2003 Type 2 Diabetes and
Associated Complications in Primary Care in
Canada The Impact of Duration of Disease on
Morbidity Load.
5
Proportion of patients with cardiovascular
disease increases with duration of type 2 diabetes
lt2
3-5
6-9
10-14
15
Years T2DM
Harris,S et al. CDA 2003 Type 2 Diabetes and
Associated Complications in Primary Care in
Canada The Impact of Duration of Disease on
Morbidity Load.
6
Proportion of patients with microvascular disease
increases with duration of type 2 diabetes
lt2
3-5
6-9
10-14
15
Years T2DM
Harris,S et al. CDA 2003 Type 2 Diabetes and
Associated Complications in Primary Care in
Canada The Impact of Duration of Disease on
Morbidity Load.
7
Classification
8
UKPDS decreased risk of diabetes-related
complications associated with a 1 decrease in A1C
Observational analysis from UKPDS study data
Any diabetes- related endpoint
Diabetes- related death
All cause mortality
Peripheral vascular disease
Micro- vascular disease
Myocardial infarction
Cataract extraction
Stroke
Percentage decrease in relative risk
corresponding to a 1 decrease in HbA1C
12
14
14

19

21
21




37
43


Adapted from Stratton IM, et al. UKPDS 35. BMJ
2000 321405412.
9
UKPDS the benefits of improved
glycemic control

• Improved glycemic control significantly reduces
  risk
• of diabetes-related complications
• UKPDS results indicated that a 1 reduction in
  A1C
• would reduce the risk of microvascular
  complications
• by 37, but have less effect (16) on
• macrovascular complications
• Further improvement in sustained glycemic
  control
• and reduction in the burden of cardiovascular
• disease are needed

Stratton IM, et al. UKPDS 35. BMJ 2000
321405412.
10
Proportion of patients with A1C lt 7.0 on
monotherapy at 3, 6 and 9 years
Overweight patients
100
Diet
Insulin
Metformin
Sulfonylurea
80
60
Proportion of patients ()
50
40
20
0
3
6
9
3
6
9
3
6
9
3
6
9
Years from randomization
Error bars 95 CI
Turner RC, et al. UKPDS 49. JAMA 1999
28120052012.
11
The UKPDS demonstrated progressive decline of
?-cell function over time
100
100
Start of treatment
80
80
60
60
?-cell function ()
40
40
P lt 0.0001
20
0
10
9
8
7
6
5
4
3
2
1
1
2
3
4
5
6
Time from diagnosis (years)
HOMA model, diet-treated n 376
Adapted from Holman RR. Diabetes Res Clin Pract
1998 40 (Suppl.)S21S25.
12
Essential Changes For T2DM CDA Guidelines 1998
vs. 2003

• Testing for fasting glucose threshold lowered
  from 6.1 to 5.7 mmol/L, but diagnostic levels the
  same (7 come 11).
• Treatment is not only directed to glucose control
• Lifestyle, BP, Lipids, and microalbumin also
  targeted.
• Time to reach goal A1c limited 6-12 months.
• Goals are lower blood glucose and A1c (7 and
  6 where feasible).
• Initial Medication consider two agents to start.
• Recommended sequence of choices is different
• Earlier use of insulin recommended.
• Vascular protection (cardiovascular disease
  prevention) is targeted.

13
Canadian Diabetes Association 2003 Clinical
Practice Guidelines for the Prevention and
Management of Diabetes in Canada
Management of Hyperglycemia in Type 2 Diabetes
14
Lifestyle Intervention

• The first step in treating type 2 diabetes
• Nutrition therapy and exercise can improve
  glycemic control
• Success of lifestyle intervention related to
• patients initial fasting plasma glucose level
• amount of weight loss achieved by patient
• Only a minority of patients are able to attain
  treatment
• targets using lifestyle intervention alone.

15
UKPDS 7 Response of FPG to Diet Therapy in
Newly Diagnosed Patients

• N 3044, newly diagnosed patients
• FPG at diagnosis 12.1/- 3.7 mmol/L
• Diet counseling
• Patients with FPG 10-12 mmol/L needed reduction
  of 28
• ideal body weight to attain FPG lt6 mmol/L
• 16 achieved FPG lt6 after 3 months
• in the group presenting with FPGs of 6-8 mmol/L
  50
• met this target
• in the group presenting with FPGs of 16-22
  mmol/L
• only 10 were successful

Metabolism, 1990 39(3) 905-912
16
Glycemic Targets

• A1C Fasting/premeal 2h PPG
• mmol/L mmol/L
• Target
• (for most patients) lt7 4
  7 5 10
• Normal range
• (if achievable safely) lt6 4
  6 5 8
• Treatment goals and strategies must be tailored
  to the patient, with consideration given to
  individual risk factors.

17
Antihyperglycemic Agents
18
Primary Sites of Action of Oral
Antihyperglycemic Agents
Stomach
Gut
I
Glucose (G)
G
I
Adipose tissue
I
G
Insulin
G
I
G
G
I
Pancreas
G
I
G
I
G
I
G
I
Muscle
G
I
G
G
Liver
Adapted from Kobayashi M. Diabetes Obes Metab
1999 1 (Suppl. 1)S32S40.Nattrass M Bailey
CJ. Baillieres Best Pract Res Clin Endocrinol
Metab 1999 13309329.
19
Key Recommendations

• Antihyperglycemic agents should be initiated if
  glycemic targets not met after 2-3 months of
  lifestyle intervention
• Antihyperglycemic agents should be started
  concomitantly with lifestyle if A1C levels are
  greater than 9
• The lag period before adding other agent(s)
  should be kept to a minimum to achieve glycemic
  targets within 6-12 months
• Unless contraindicated, metformin should be used
  first line other agents should be considered in
  the order they appear in the treatment algorithm
• Insulin therapy should be initiated if targets
  cannot be achieved with lifestyle changes and
  oral therapy

20
New Treatment Options for Type 2 Diabetes
Stepwise treatment
Diet/exercise
Oralmonotherapy
Oral combination
Insulin
Oral /- insulin
21
Management of Hyperglycemia in Type 2 Diabetes
22
When used in combination with insulin, insulin
sensitizers may increase the risk of edema or
CHF. The combination of an insulin sensitizer
and insulin is currently not an approved
indication in Canada.
23
Dose-Response Curve
Dose-Response Curve
Dose-Response Curve
Dose-response curve showing GI related effects
Riddle M. Combining
sulfonylureas
and other oral agents.
Am J of Med
. 2000 108(6A)15S-22S
.
24
Clinical assessment and initiation of nutrition
and physical activity
Marked hyperglycemia (A1C ?9.0)
Mild to moderate hyperglycemia (A1C lt9.0)

Basal and/or preprandial insulin
Non-overweight (BMI ?25 kg/m2)
Overweight (BMI ?25 kg/m2)
2 antihyperglycemic agents from different classes

• biguanide
• insulin sensitizer
• insulin secretagogue
• insulin
• alpha-glucosidase
• inhibitor

Biguanide alone or in combination with 1 of
1 or 2 antihyperglycemic agents from
different classes

• insulin sensitizer
• insulin secretagogue
• insulin
• alpha-glucosidase
• inhibitor

• biguanide
• insulin sensitizer
• insulin secretagogue
• insulin
• alpha-glucosidase
• inhibitor

L I F E S T Y L E

Add an oral antihyperglycemic agent from a
different class or insulin
Add a drug from a different class or Use
insulin alone or in combination with
Intensify insulin regimen or add

• biguanide
• insulin
• secretagogue
• insulin sensitizer
• alpha-glucosidase
• inhibitor

• biguanide
• insulin secretagogue
• insulin sensitizer
• alpha-glucosidase inhibitor

Timely adjustments to and/or additions of oral
antihyperglycemic agents and/or insulin should be
made to attain target A1C within 6 to 12 months
25
Key Changes

• A1C lt7 (lt 6 if can be achieved safely)
• Aim to achieve targets within 6-12 months
• Start with combination therapy or insulin for
  patients with A1C gt 9
• Consider insulin at any stage of treatment
• Vascular protection to further reduce
  cardiovascular risk

26
Rational for Insulin Sensitizers over Insulin
Secretagogues for Second Choice Pharmacotherapy
27
Insulin Sensitizers vs. Insulin Secretagogues for
Second Choice Pharmacotherapy

• Initial choice of medication should be between
  Metformin and a TZD. The only outcome data,
  (UKPDS) in obese, showed metformin reduced
  cardiovascular disease.
• But no long-term outcome study to date using a
  TZD.
• Additional medication, if metformin had been
  started, would be a TZD as one gains the
  pleiotrophic benefits
• Reduction of FFA
• Reduction of inflammatory markers (PAI-1, CRP,
  etc.)
• Reduction of microalbuminuria
• Reduction in Blood pressure
• Reduction in insulin resistance
• Possible prolonged effectiveness beta cell
  survival

28
What Should Pharmacists Do?

• Of course, knowledge of true efficacy and side
  effects of all medication is essential.
• Pharmacists should not just produce a shopping
  list of every side effect ever known to man.
• Goal is to encourage patients to take meds, not
  to give them reasons not to!
• Understand and teach effective home glucose
  monitoring for T2DM and T1DM
• Use internet to provide up to date information

29
Monitoring Glycemic Control

• A1C should be measured approximately every 3
  months
• Testing should be both pre and post meals
• SMBG should be recommended as an essential part
  of daily diabetes management for all people using
  insulin or oral antihyperglycemic agents

All people with diabetes should be taught how to
self-manage their diabetes, including SMBG
30
Self-Monitoring of Blood Glucose

• All people with DM, who are able should be taught
  how to self-manage including SMBG Grade A, Level
  1A
• Testing frequency should be individualized. For
  most people with type 2 DM on insulin or OHAs,
  SMBG at least once daily is recommended Grade C,
  Level 3 More frequent testing may be needed to
  alter behavior or make treatment changes.
• SMBG should include both preprandial and 2 hours
  postprandial Grade D, Consensus
• Before, during and especially after exercise

31
Hypoglycemia

• Defined as a blood glucose of less than 4.0
  mmol/l
• Should be documented by home testing.
• Occurs essentially only with insulin
  secretagogues and insulin

32
Severe Hypoglycemia Definition

• The individual requires assistance of another
  person
• Unconsciousness may occur.
• Plasma glucose is typically lt 2.8 mmol/L

33
Prevention of the ComplicationsMacrovascular

• First priority is the reduction in cardiovascular
  risk through multifaceted approach including
• 1. Lifestyle changes
• Stop smoking
• Healthy eating
• Regular physical activity

34
Prevention of the ComplicationsMacrovascular (2)

• 2. Pharmacological interventions
• ACEI
• ASA
• Optimize BP and glucose control
• Optimize lipids

35
Target lipid levels in diabetes

• Risk Level LDL-C TC/HDL-C
• (mmol/L) (mmol/L)
• High 2.5 4.0
• Intermediate 3.5 5.0

CDA guidelines - 2003
36
Achieving Lipid Goals

• 1. Where LDL is above target use a statin
• 2. In high risk patients with TG levels of 1.5 to
  4.5 mmol/L and LDL-C at target, use a statin or a
  fibrate.
• 3. Where marked hyper-triglyceridemia (gt4.5) use
  a fibrate.
• 4. When monotherapy fails to achieve lipid
  targets, add a second drug from another class.

37
Treating Hypertension

• Goal BP is ?130/80
• This goal is lower than that of the non-diabetic.
• Measure BP at every visit
• If one therapy does not achieve goal, add another
  agent.

38
Antihypertensive Therapy -Choices of Agents in
Absence of Nephropathy(Grade D, Consensus for
the order)

• ACEI (Grade A, Level 1A)
• ARB (Grade A, Level 1A for co-existent LVH,
  Grade B, Level 2 if no LVH)
• Cardioselective beta-blocker (Grade A, Level 2)
• A thiazide-like diuretic (Grade a, Level 1a)
• A long-acting calcium-channel blocker (Grade B,
  Level 2)
• Alpha blockers not recommended as first-line
  agent, but may be used as additional agents

39
ASA Therapy
Unless contraindicated, low-dose ASA therapy
(80-325 mg/day) is recommended in all patients
with diabetes with evidence of CVD, as well as
for those individuals with atherosclerotic risk
factors that increase their likelihood of CV
events (Grade A, Level 1a)
40
Intra-subject Variability Basal Insulin Glargine
Subject 2
Subject 3
Subject 7
Subject 9
Subject 18
Subject 19
Subject 22
Concentrations mlU/mL
Subject 14
Subject 28
Subject 34
Subject 27
Subject 35
Time h
Scholtz et al. Diabetes 199948(suppl 1)A97.
Abst 416 Study 1012
41
Please note There is no narration with this
slide Glargine - Overall Summary

• Insulin Glargine has the following clinical
  benefits
• Once-daily dosing because of its prolonged
  duration of action and smooth, peakless
  time-action profile
• Comparable or better glycemic control (FBG)
• Lower risk of clinically important hypoglycemic
  events
• Safety profile similar to that of human insulin

42
Thank You.

• Questions?