LONG TERM BENEFITS OF ORAL AGENTS J Robin

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 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 A 1 C of 9% A 1 C < 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 (A 1 C<9. 0%) Overweight Non-overweight Biguanide alone or in combination 1 or 2 antihyperglycemic agents from different classes If not at target Add a drug from a different class or use insulin alone or in combination Marked hyperglycemia (A 1 C 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 A 1 C 7. 0%, patients should aim for FPG, preprandial and postprandial PG targets

Burden of Poor Control - Cost

Burden of Poor Control - Cost Ø Estimate annual cost to health plans by level of glycemic control Ø 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): S 1 -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 TZD RECEPTOR GLUCOSE TZD GLUT-4 PPAR DNA Saltiel, Olefsky Diabetes 1996; 45: 1661– 9. RNA

Hb. A 1 c (%) Durability of Glycemic Control with Pioglitazone Long Term Einhorn D et al. Diabetes 2001; 50 (suppl 2): A 111

Metformin & Pioglitazone Study - Open Label Extension Change in Hb. A 1 c (%) 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): S 1 -29.

Natural History of Type 2 Diabetes Henry. Am J Med 1998; 105(1 A): 20 S-6 S.

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 Henry. Am J Med 1998; 105(1 A): 20 S-6 S. Secretagogues 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 A 1 C 7. 0%, patients should aim for FPG, preprandial and postprandial PG targets