LONG TERM BENEFITS OF ORAL AGENTS

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LONG TERM BENEFITS OF ORAL AGENTS
J. Robin Conway M.D. Diabetes Clinic Smiths
Falls, ON www.diabetesclinic.ca
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Long Term Benefits of Oral Agents

• Robin Conway M.D.

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Physical Activity and Diabetes

• 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.
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Nutrition Therapy

• People with diabetes should
• Receive nutrition counseling by a registered
  dietitian
• Receive individualized meal planning
• Follow Canadas Guidelines for Healthy Eating
• People on intensive insulin should also be taught
  to adjust the insulin for the amount of
  carbohydrate consumed

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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 BMI Suggested starting agent
lt 9 BMI ? 25 Biguanide alone or in combination
lt 9 BMI lt 25 1 or 2 agents from different classes
? 9 -- 2 agents from different classes or insulin basal and/or preprandial
Intensify to reach targets in 6-12 months
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Management of Hyperglycemia in Type 2 Diabetes
Patients
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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
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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
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Burden of Poor Control - Cost
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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

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Oral Antihyperglycemic Agents Biguanides

• Decreases hepatic glucoseproduction, enhances
  peripheral glucose uptake
• 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

LIVER
MUSCLE
Meltzer et al CMAJ 1998159(Suppl)S1-29.
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Oral Antihyperglycemic Agents Thiazolidinediones
(TZDs)

• Decrease insulinresistance
• 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

MUSCLE
LIVER
ADIPOSE TISSUE
Plosker, Faulds Drugs 199957410-32. Balfour,
Plosker Drugs 199957921-30.
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Thiazolidinediones Mechanism of Insulin
Sensitization
INSULIN
INSULIN
RECEPTOR
GLUCOSE
GLUT-4
PPAR?
RNA
DNA
Saltiel, Olefsky Diabetes 19964516619.
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Durability of Glycemic Control with Pioglitazone
Long Term
HbA1c ()
Einhorn D et al. Diabetes 200150 (suppl2)A111
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Metformin Pioglitazone Study - Open Label
Extension
Change in HbA1c ()
Change in fasting glucose (mmol/L)
Einhorn et al. Clin Therapeutics 2000121395-1409
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Oral Antihyperglycemic Agents Sulfonylureas

• Stimulate pancreatic insulin release
• e.g., First-generation tolbutamide,
  chlorpropamide, acetohexamide
• e.g., Second-generation Glyburide, gliclazide
• Secondary failure a problem
• Weight gain, risk of hypoglycemia

PANCREAS
Meltzer et al CMAJ 1998159(Suppl)S1-29.
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Natural History of Type 2 Diabetes
Henry. Am J Med 1998105(1A)20S-6S.
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Oral Antihyperglycemic Agents Alpha-glucosidase
inhibitors

• Slows gut absorptionof starch and sucrose
• Attenuates postprandial increases in blood
  glucose levels
• e.g., Acarbose
• GI side effects
• Not associated with hypoglycemia or weight gain

INTESTINE
Salvatore, Giugliano Clin Pharmacokinet
19963094-106.
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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
20
Natural History of Type 2 Diabetes
Metformin/Thiazolidinediones
Secretagogues
Lifestyle
Henry. Am J Med 1998105(1A)20S-6S.
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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