long term benefits of oral agents

Long Term Benefits of Oral Agents Robin Conway M.D... Pharmacologic Management of Type 2 Diabetes • Add anti-hyperglycemic agents if: Diet & exercise therapy do not achieve targets afte

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

• 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

Type Recommendation Example

Aerobic – especially

exercise each week

• spread out over at least 3 consecutive days

non-• gradually increase to 4 hours or more a week

• sessions should be at least 10 minutes at a time

Brisk walking Biking

Raking leaves Continuous swimming Dancing

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%

Intensify to reach targets in 6-12 months

Clinical assessment and initiation of nutrition therapy and physical activityMild to moderate hyperglycemia (A1C<9.0%) Marked hyperglycemia (A1C ≥ 9.0%)

Basal and/or preprandial insulin

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

Combined rosiglitazone and metformin 1.0 – 1.5 Antiobesity agent (orlistat) 0.5

Targets for Glycemic Control

* Treatment goals and strategies must be tailored to the patient, with consideration given to individual risk factors

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

To achieve an A1C ≤ 7.0%, patients should aim for

FPG, preprandial and postprandial PG targets

Burden of Poor Control - Cost

4500 4700 4900 5100 5300 5500 5700 5900 6100 6300 6500

Burden of Poor Control - Cost

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

Oral Antihyperglycemic Agents:

Biguanides

• Decreases hepatic glucose

production, 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

MUSCLE LIVER

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

MUSCLE

ADIPOSE TISSUE LIVER

Oral Antihyperglycemic Agents:

Thiazolidinediones (TZDs)

• Decrease insulin

resistance

– 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

INSULIN

RECEPTOR

RNA DNA

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

Durability of Glycemic Control

with Pioglitazone Long Term

Metformin & Pioglitazone Study

- Open Label Extension

Hb1cfasting glucose

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

Normal Impaired glucose

tolerance Type 2 diabetes

Time

Insulin resistance

Insulin production

Glucose level

β -cell dysfunction

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

Oral Antihyperglycemic Agents: Alpha-glucosidase inhibitors

• Slows gut absorption

of 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

Combined rosiglitazone and metformin 1.0 – 1.5 Antiobesity agent (orlistat) 0.5

Insulin production

Glucose level

β -cell dysfunction

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

Lifestyle

Metformin/Thiazolidinediones

Targets for Glycemic Control

* Treatment goals and strategies must be tailored to the patient, with consideration given to individual risk factors

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

To achieve an A1C ≤ 7.0%, patients should aim for

FPG, preprandial and postprandial PG targets