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Drug therapy in diabetes


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Drug therapy in diabetes

  1. 1. Drug therapy in Diabetes
  2. 2. Diagnosis of Diabetes Fasting Random OGTT(2h) Normal <6 <7.8 Impair 6.1 – 7 7.8- 11.1 Diabetes >7 >11.1 + symptoms >11.1
  3. 3. Aims of management <ul><li>To achieve near normal glycaemia </li></ul><ul><li>Short term- to prevent symptoms of hyper & hypo </li></ul><ul><li>Long term- to prevent complications </li></ul><ul><li>Good quality of life, near normal life expectancy </li></ul>
  4. 4. Targets for non-pregnant patients <ul><li>HbA1c - NICE 6.5-7.5% </li></ul><ul><li>- ADA <7% </li></ul><ul><li>- IDF <6.5% </li></ul><ul><li>BP - <130/80 </li></ul><ul><li>Cholesterol- LDL <2.6 (mM) </li></ul><ul><li> HDL >1.1 </li></ul><ul><li> TG <1.7 </li></ul>
  5. 5. Types of Insulin <ul><li>Short acting - Soluble / Neutral insulin </li></ul><ul><li> Insulin aspart </li></ul><ul><li>Insulin lispro </li></ul><ul><li>Intermediate acting - Isophane </li></ul><ul><li>Long acting - Insulin Zinc suspension </li></ul><ul><li> new insulin analogue - Glargine </li></ul><ul><li> Detemir </li></ul><ul><li>Biphasic- mixture of short and intermediate </li></ul><ul><li> Biphasic lispro </li></ul><ul><li> Biphasic Isophane </li></ul>
  6. 6. Types of Insulin Insulin Lispro Aspart Neutral/ regular Isophane ultratard Glargine Onset 10-20′ 30′ 1h 4h 2-4h Peak 1h 1-3h 4-6h 6-18h peak less Duration 3-5h 4-8h 8-14h 24h 20-24h
  7. 7. Soluble insulin / neutral /clear <ul><li>Names - Human actrapid/ Humulin S </li></ul><ul><li>Species- Bovine, porcine, human </li></ul><ul><li>Following s/c injection </li></ul><ul><li>Onset of action – 30 min </li></ul><ul><li> Peak- 1-3 hours </li></ul><ul><li> Duration- 4-8 hours </li></ul><ul><li>Only insulin suitable for intravenous route –plasma half life < 5 min, required continuous infusion </li></ul><ul><li>Used in diabetes Ketoacidosis </li></ul>
  8. 8. Sites of injections - Subcutaneous <ul><li>Thighs </li></ul><ul><li>Upper buttocks </li></ul><ul><li>Abdomen </li></ul><ul><li>Arms </li></ul><ul><li>Important to rotate the site </li></ul><ul><li>Rate of absorption may be significantly different – faster from arm and abdomen than from thigh and buttock </li></ul>
  9. 9. Routes of Administration <ul><li>Subcutaneous for long term regular use </li></ul><ul><li>Intravenous infusion in acute conditions- diabetes Ketoacidosis, Perioperative period, Hyperosmolar Nonketotic state ONLY NEUTRAL/ CLEAR INSULIN CAN BE USED </li></ul><ul><li>Continuous subcutaneous insulin infusion via pump – neutral </li></ul><ul><li>Intraperitoneal – Peritoneal dialysis patients </li></ul><ul><li>Inhaled insulin- experimental </li></ul>
  10. 10. Untoward effect of insulin <ul><li>Hypoglycaemia </li></ul><ul><li>Weight gain- anabolic hormone </li></ul><ul><li>Lipohypertrophy- injection to same site </li></ul><ul><li>Insulin oedema </li></ul><ul><li>Transient deterioration in retinopathy </li></ul><ul><li>Insulin neuritis – actively regenerating neurone, uncommon </li></ul><ul><li>Postural hypotension </li></ul>
  11. 11. Example injections Intermediate/long acting bedtime bedtime injections Biphasic insulin Biphasic insulin Short acting Short acting Short acting breakfast lunch dinner breakfast lunch dinner
  12. 12. Recurrent Hypo <ul><li>? Required dose adjustment </li></ul><ul><li>? Right insulin/ injection technique </li></ul><ul><li>? Meal/ fasting related </li></ul><ul><li>? Injections sites </li></ul><ul><li>? Exercise </li></ul><ul><li>Unexplained - ?autonomic neuropathy </li></ul>
  13. 13. Sick day rules <ul><li>never stop insulin </li></ul><ul><li>monitor more frequently </li></ul><ul><li>maintain your hydration </li></ul><ul><li>Check for ketones </li></ul><ul><li>Know when & how to call for help </li></ul>
  14. 14. Oral Medications to Treat Type 2 Diabetes
  15. 15. Major Classes of Medications <ul><li>sensitize the body to insulin +/- control hepatic glucose production </li></ul><ul><li>stimulate the pancreas to make more insulin </li></ul><ul><li>slow the absorption of starches </li></ul><ul><ul><li>Thiazolidinediones </li></ul></ul><ul><ul><li>Biguanides </li></ul></ul><ul><ul><li>Sulfonylureas </li></ul></ul><ul><ul><li>Meglitinides </li></ul></ul><ul><ul><li>Alpha-glucosidase </li></ul></ul><ul><ul><li>inhibitors </li></ul></ul>
  16. 16. Thiazolidinediones <ul><li>↓ insulin resistance by making muscle and adipose cells more sensitive to insulin. They also suppress hepatic glucose production. </li></ul><ul><li>Efficacy </li></ul><ul><ul><li>↓ fasting plasma glucose ~1.9-2.2 mmol/L </li></ul></ul><ul><ul><li>Reduce A1C ~0.5-1.0% </li></ul></ul><ul><ul><li>6 weeks for maximum effect </li></ul></ul><ul><li>Other Effects </li></ul><ul><ul><li>Weight gain, oedema </li></ul></ul><ul><ul><li>Hypoglycemia (if taken with insulin or agents that stimulate insulin release) </li></ul></ul><ul><ul><li>Contraindicated in patients with abnormal LFT or CHF </li></ul></ul><ul><ul><li>Improves HDL cholesterol and plasma triglycerides; usually LDL neutral </li></ul></ul><ul><li>Medications in this Class: pioglitazone (Actos), rosiglitazone (Avandia), [troglitazone (Rezulin) - taken off market due to liver toxicity] </li></ul>
  17. 17. Biguanides <ul><li>Biguanides ↓ hepatic glucose production and increase insulin-mediated peripheral glucose uptake. </li></ul><ul><li>Efficacy </li></ul><ul><ul><li>Decrease fasting plasma glucose 60-70 mg/dl (3.3-3.9 mmol/L) </li></ul></ul><ul><ul><li>Reduce A1C 1.0-2.0% </li></ul></ul><ul><li>Other Effects </li></ul><ul><ul><li>Diarrhea and abdominal discomfort </li></ul></ul><ul><ul><li>Lactic acidosis if improperly prescribed </li></ul></ul><ul><ul><li>Cause small decrease in LDL cholesterol level and triglycerides </li></ul></ul><ul><ul><li>No specific effect on blood pressure </li></ul></ul><ul><ul><li>No weight gain, with possible modest weight loss </li></ul></ul><ul><ul><li>Contraindicated in patients with impaired renal function </li></ul></ul><ul><ul><li>Medications in this Class: metformin (Glucophage), metformin hydrochloride extended release (Glucophage XR) </li></ul></ul>
  18. 18. Sulfonylureas <ul><li>Sulfonylureas increase endogenous insulin secretion </li></ul><ul><li>Efficacy </li></ul><ul><ul><li>Decrease fasting plasma glucose 3.3-3.9 mmol/L </li></ul></ul><ul><ul><li>Reduce A1C by 1.0-2.0% </li></ul></ul><ul><li>Other Effects </li></ul><ul><ul><li>Hypoglycemia </li></ul></ul><ul><ul><li>Weight gain </li></ul></ul><ul><ul><li>No specific effect on plasma lipids or blood pressure </li></ul></ul><ul><ul><li>Generally the least expensive class of medication </li></ul></ul><ul><li>Medications in this Class: </li></ul><ul><ul><li>First generation : chlorpropamide , tolazamide, acetohexamide , tolbutamide </li></ul></ul><ul><ul><li>Second generation : glyburide , glimepiride , glipizide </li></ul></ul>
  19. 19. Meglitinides <ul><li>stimulate insulin secretion (rapidly and for a short duration) in the presence of glucose. </li></ul><ul><li>Efficacy </li></ul><ul><ul><li>↓ peak postprandial glucose </li></ul></ul><ul><ul><li>↓ plasma glucose 3.3-3.9 mmol/L </li></ul></ul><ul><ul><li>↓ HbA1C 1.0-2.0% </li></ul></ul><ul><li>Other Effects </li></ul><ul><ul><li>Hypoglycemia (may be less than with sulfonylureas if patient has a variable eating schedule) </li></ul></ul><ul><ul><li>Weight gain </li></ul></ul><ul><ul><li>No significant effect on plasma lipid levels </li></ul></ul><ul><ul><li>Safe at higher levels of serum Cr than sulfonylureas </li></ul></ul><ul><li>Medications in this Class: repaglinide , nateglinide </li></ul>
  20. 20. Alpha-glucosidase Inhibitors <ul><li>Alpha-glucosidase inhibitors block the enzymes that digest starches in the small intestine </li></ul><ul><li>Efficacy </li></ul><ul><ul><li>↓ peak postprandial glucose 2.2-2.8 mmol/L </li></ul></ul><ul><ul><li>↓ fasting plasma glucose 1.4-1.7 mmol/L </li></ul></ul><ul><ul><li>Decrease A1C 0.5-1.0% </li></ul></ul><ul><li>Other Effects </li></ul><ul><ul><li>Flatulence or abdominal discomfort </li></ul></ul><ul><ul><li>No specific effect on lipids or blood pressure </li></ul></ul><ul><ul><li>No weight gain </li></ul></ul><ul><ul><li>Contraindicated in patients with inflammatory bowel disease or cirrhosis </li></ul></ul><ul><li>Medications in this Class: acarbose , miglitol </li></ul>
  21. 21. Efficacy of Monotherapy with Oral Diabetes Agents DeFronzo Annals of Internal Medicine 1999;131:281-303 Nathan N Engl J Med 2002; 347:1342-1349
  22. 22. Treatment of Type 2 Diabetes Diagnosis Therapeutic Lifestyle Change Combination Therapy - Oral Drug with Insulin Combination Therapy - Oral Drugs Only Monotherapy
  23. 23. <ul><li>Sulfonylurea + Biguanide </li></ul><ul><li>Glyburide + Metformin - Glucovance </li></ul><ul><li>Glipizide + Metformin - Metaglip </li></ul><ul><li>Thiazolidinedione + Biguanide </li></ul><ul><li>Rosiglitazone + Metformin - Avandamet </li></ul>Combination Therapy for Type 2 Diabetes Fixed Combination Pills
  24. 24. Combination Therapy for Type 2 Diabetes Biguanides Sulfonylureas Insulin Alpha-glucosidase Inhibitors Meglitinide Thiazolidinediones
  25. 25. Clinic Checklists <ul><li>Glycaemic control- home monitoring, HbA1c, inj site, hypo </li></ul><ul><li>Diet, exercise, Smoking, alcohol </li></ul><ul><li>BP </li></ul><ul><li>Weight </li></ul><ul><li>Macrovascular- CVA, IHD </li></ul><ul><li>Microvascular- Retinopathy, microalbuminuria, neuropathy </li></ul><ul><li>Foot </li></ul><ul><li>Lipid profile, renal function, TSH </li></ul>
  26. 26. Special circumstances <ul><li>Intercurrent illness </li></ul><ul><li>Peri-operative period </li></ul><ul><li>Pregnancy </li></ul><ul><li>Childhood and adolescents </li></ul><ul><li>Others- travelling across time zones </li></ul><ul><li> Exercise </li></ul><ul><li> Alcohol </li></ul><ul><li>Driving </li></ul>
  27. 27. New developments
  28. 28.