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 type 2 • 150 minutes of moderate-intensity exercise each week • spread out over at least 3 non- consecutive days • 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 Water aerobics Resistance – all persons with diabetes, including elderly • 3 times a week • start with 1 set of 10-15 repetitions • progress to 2 sets of 10-15 • then 3 sets of 8 Weight lifting Exercise with weight machines 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 A1 C & 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 classes 1 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 Class Expected decrease in A1C with monotherapy Αlpha-glucosidase inhibitor 0.5 – 0.8 Biguanide 1.0 – 1.5 Insulin Depends on regimen Insulin secretagogues 1.0 – 1.5 0.5 for nateglinide Insulin sensitizers (TZDs) 1.0 – 1.5 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 6 7 8 9 10 HbA1c cost/patient/year Diabetes only Diab, HT, Heart dis 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 4500 9500 14500 19500 24500 6 7 8 9 10 HbA1c cost/patient/year Diabetes only Diab, HT, Heart dis [...]... failure a problem – Weight gain, risk of hypoglycemia Meltzer et al CMAJ 1998;159(Suppl):S1-29 Natural History of Type 2 Diabetes Insulin resistance Glucose level Insulin production β -cell dysfunction Normal Impaired glucose tolerance Henry Am J Med 1998;105(1A):20S-6S Type 2 diabetes Time Oral Antihyperglycemic Agents: Alpha-glucosidase inhibitors • Slows gut absorption of starch and sucrose – Attenuates... 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 PPARγ DNA Saltiel, Olefsky Diabetes 1996;45:1661–9 RNA Durability of Glycemic Control with Pioglitazone Long Term 10.5 10 HbA1c (%) 9.5 rollover placebo 9 8.5 rollover pioglitazone 8 7.5 baseline endpoint week 12 week 24.. .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: ... (suppl2):A111 Metformin & Pioglitazone Study - Open Label Extension 0 0 end of DB STUDY week 24 week 48 week 72 -0.2 -0.5 -0.4 -1 -0.6 -1.5 -0.8 -2 -1 Hb1c fasting glucose -2.5 -1.2 -3 -1.4 -3.5 -1.6 -4 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... 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 Αlpha-glucosidase inhibitor Expected decrease in A1C with monotherapy 0.5 – 0.8 Biguanide 1.0 – 1.5 Insulin Depends on regimen Insulin secretagogues Insulin sensitizers (TZDs)... metformin 1.0 – 1.5 Antiobesity agent (orlistat) 0.5 Class • 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 Insulin Insulin resistance Glucose level β -cell dysfunction . 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. 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. 1996;45:1661–9. Thiazolidinediones: Mechanism of Insulin Sensitization TZD PPARγ INSULIN GLUT-4 GLUCOSE Durability of Glycemic Control with Pioglitazone Long Term 7.5 8 8.5 9 9.5 10 10.5 baseline endpoint