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LONG TERM BENEFITS OF ORAL AGENTS
J. Robin Conway M.D.
Diabetes Clinic
Smiths Falls, ON
www.diabetesclinic.ca
Long Term Benefits of Oral
Agents
Robin Conway M.D.
Physical Activity and Diabetes
A1C
(%)
FPG/preprandial
(mmol/L)
Target for most patients
 7.0
4.0 – 7.0
5.0 – 10.0
Normal range
(if it can be safely achieved)
 6.0
4.0 – 6.0
5.0 – 8.0
2h Postprandial
(mmol/L)
• For people who have not previously exercised regularly and are at
risk of CVD, an ECG stress test should be considered prior to
starting an exercise program
Testing is particularly important before, during
and for many hours after exercise.
Nutrition Therapy
People with diabetes should:
• Receive nutrition counseling by a registered
dietitian
• Receive individualized meal planning
• Follow Canada’s Guidelines for Healthy Eating
• People on intensive insulin should also be taught
to adjust the insulin for the amount of
carbohydrate consumed
Pharmacologic Management of
Type 2 Diabetes
• Add anti-hyperglycemic agents if:
Diet & exercise therapy do not achieve targets
after 2-3 month trial
Or newly diagnosed and has an A1C of  9%
A1C
<
9%

9%
& BMI
Suggested starting agent
BMI  25 Biguanide alone or in combination
BMI < 25 1 or 2 agents from different classes
--
2 agents from different classes or
insulin basal and/or preprandial
Intensify to reach targets in 6-12 months
Management of Hyperglycemia in Type 2
Diabetes Patients
Clinical assessment and initiation of nutrition therapy and physical activity
Mild to moderate hyperglycemia (A1C<9.0%)
Overweight
Non-overweight
Biguanide alone
or in
combination
1 or 2
antihyperglycemic
agents from different
classes
If not at target
If not at target
Add a drug from a different class or
use insulin alone or in combination
Marked hyperglycemia (A1C  9.0%)
2 antihyperglycemic
agents from different
classes
If not at target
Add an oral
antihyperglycemic agent
from a different class or
insulin
Basal and/or
preprandial
insulin
If not at target
Intensify insulin
regimen or add
antihyperglycemic
agents
Oral Agents for Type 2 Diabetes
• Combination at less than maximal doses result in
more rapid improvement of blood glucose
• Counsel patients about hypoglycemia prevention and
treatment
SMBG is recommended at least once daily
Targets for Glycemic Control
* Treatment goals and strategies must be tailored to the patient, with consideration
given to individual risk factors
To achieve an A1C  7.0%, patients should aim for
FPG, preprandial and postprandial PG targets
Burden of Poor Control - Cost
Burden of Poor Control - Cost
 Estimate annual
cost to health
plans by level of
glycemic control
 Determine effect
of Improved
Glycemic Control
on Health Care
Utilization and
Costs
Oral Antihyperglycemic Agents:
Biguanides
• Decreases hepatic glucose
production, enhances
peripheral glucose uptake
–
–
–
–
–
LIVER
MUSCLE
May reduce insulin resistance in the periphery
e.g., Metformin
Contraindicated in renal/hepatic insufficiency
May cause GI side effects
Not associated with hypoglycemia, may promote weight
loss
Meltzer et al CMAJ 1998;159(Suppl):S1-29.
Oral Antihyperglycemic Agents:
Thiazolidinediones (TZDs)
• Decrease insulin
resistance
MUSCLE
LIVER
ADIPOSE
TISSUE
– Increase insulin-dependent
glucose disposal, decrease hepatic glucose production
– e.g., Pioglitazone, rosiglitazone
– Pioglitazone has a positive effect on lipids
– Not associated with hypoglycemia
– Possible URI, headache, edema, weight gain and
reduction in hemoglobin
Plosker, Faulds Drugs 1999;57:410-32. Balfour, Plosker Drugs 1999;57:921-30.
Thiazolidinediones: Mechanism of
Insulin Sensitization
INSULIN
INSULIN
TZD
RECEPTOR
GLUCOSE
TZD
GLUT-4
PPAR
DNA
Saltiel, Olefsky Diabetes 1996;45:1661–9.
RNA
HbA1c (%)
Durability of Glycemic Control
with Pioglitazone Long Term
Einhorn D et al. Diabetes 2001;50 (suppl2):A111
Metformin & Pioglitazone Study
- Open Label Extension
Change in HbA1c (%)
Change in fasting glucose (mmol/L)
Einhorn et al. Clin Therapeutics 2000;12:1395-1409
Oral Antihyperglycemic Agents:
Sulfonylureas
• Stimulate pancreatic
insulin release
PANCREAS
– e.g., First-generation: tolbutamide, chlorpropamide,
acetohexamide
– e.g., Second-generation: Glyburide, gliclazide
– Secondary failure a problem
– Weight gain, risk of hypoglycemia
Meltzer et al CMAJ 1998;159(Suppl):S1-29.
Natural History
of Type 2 Diabetes
Henry. Am J Med 1998;105(1A):20S-6S.
Oral Antihyperglycemic Agents:
Alpha-glucosidase inhibitors
• Slows gut absorption
of starch and sucrose
INTESTINE
– Attenuates postprandial increases in blood
glucose levels
– e.g., Acarbose
– GI side effects
– Not associated with hypoglycemia or weight
gain
Salvatore, Giugliano Clin Pharmacokinet 1996;30:94-106.
Oral Agents for Type 2 Diabetes
• Combination at less than maximal doses result in
more rapid improvement of blood glucose
• Counsel patients about hypoglycemia prevention and
treatment
SMBG is recommended at least once daily
Natural History
of Type 2 Diabetes
Metformin/Thiazolidinediones
Lifestyle
Secretagogues
Henry. Am J Med 1998;105(1A):20S-6S.
Insulin
Targets for Glycemic Control
* Treatment goals and strategies must be tailored to the patient, with consideration
given to individual risk factors
To achieve an A1C  7.0%, patients should aim for
FPG, preprandial and postprandial PG targets