LONG TERM BENEFITS OF ORAL AGENTS

J. Robin Conway M.D.Diabetes ClinicSmiths Falls, ONwww.diabetesclinic.ca

Long Term Benefits of Oral Agents

Robin Conway M.D.

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

A1C (%)

FPG/preprandial (mmol/L)

2h Postprandial (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

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 trialOr newly diagnosed and has an A1C of 9%

Intensify to reach targets in 6-12 months

A1C & BMI Suggested starting agent

< 9%

BMI 25 Biguanide alone or in combination

BMI < 25 1 or 2 agents from different classes

9%

--2 agents from different classes or insulin basal and/or preprandial

Clinical assessment and initiation of nutrition therapy and physical activity

Mild to moderate hyperglycemia (A1C<9.0%) Marked hyperglycemia (A1C 9.0%)

Basal and/or preprandial

insulin

Non-overweight Overweight 2 antihyperglycemic agents from different

classes1 or 2

antihyperglycemic agents from different

classes

Biguanide alone or in

combination

If not at targetIf not at target If not at target If not at target

Add a drug from a different class or use insulin alone or in combination

Add an oral antihyperglycemic agent from a different class or

insulin

Intensify insulin regimen or add

antihyperglycemic agents

Management of Hyperglycemia in Type 2 Diabetes Patients

Oral Agents for Type 2 Diabetes

SMBG is recommended at least once daily

• Combination at less than maximal doses result in more rapid improvement of blood glucose

• Counsel patients about hypoglycemia prevention and treatment

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

Meltzer et al CMAJ 1998;159(Suppl):S1-29.

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

MUSCLELIVER

Plosker, Faulds Drugs 1999;57:410-32. Balfour, Plosker Drugs 1999;57:921-30.

MUSCLE

ADIPOSE TISSUE

LIVER

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

TZD

INSULIN

RECEPTOR

RNADNA

Saltiel, Olefsky Diabetes 1996;45:1661–9.

Thiazolidinediones: Mechanism of Insulin Sensitization

TZD

PPAR

INSULIN

GLUT-4

GLUCOSE

Durability of Glycemic Control with Pioglitazone Long Term

Einhorn D et al. Diabetes 2001;50 (suppl2):A111

Hb

A1c

(%

)

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

– 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.

PANCREAS

Natural History of Type 2 Diabetes

Henry. Am J Med 1998;105(1A):20S-6S.

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

Salvatore, Giugliano Clin Pharmacokinet 1996;30:94-106.

INTESTINE

Oral Agents for Type 2 Diabetes

SMBG is recommended at least once daily

• Combination at less than maximal doses result in more rapid improvement of blood glucose

• Counsel patients about hypoglycemia prevention and treatment

Natural History of Type 2 Diabetes

Henry. Am J Med 1998;105(1A):20S-6S.

LifestyleLifestyle

Metformin/ThiazolidinedionesMetformin/Thiazolidinediones

SecretagoguesSecretagoguesInsulinInsulin

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