Understanding the Diabetes Medicine Maze. Michael R. Ikeler, M.D.

Transcription

1 Understanding the Diabetes Medicine Maze Michael R. Ikeler, M.D.

2 Understanding the Diabetes Medicine Maze

3 Understanding the Diabetes Medicine Maze Learning Objectives 1. Know blood sugar and A1C goals and understand glucose regulation 2. Overview medications and how they work 3. Individualize therapy to attain goals

4 1. Know blood sugar and A1C goals and understand glucose regulation

5 Blood Sugar Values Normal Levels: Fasting: <100 2hrs after eating: <140 Pre-Diabetes: Fasting: hrs after eating: Diabetes: Fasting: > 126 on 2 separate days or Any reading >200 There is no borderline, mild or severe diabetes there is only controlled or not controlled.

6 Two types of diabetes 1. People with type 1 diabetes don t t make any insulin, so insulin therapy is the only way to lower blood glucose levels. 2. People with type 2 diabetes don t t make enough insulin and the cells of their bodies don t t take in glucose as easily as they should.

7 A1C Level Hemoglobin A1C Blood test that measures glycosylated hemoglobin A Patients with diabetes have elevated glucose levels in their blood, which leads to increase glycosylation of hemoglobin and higher A1C levels A1C reflects the average blood glucose level over the past month time period Glucose A1C

8 Understanding the Diabetes Normal HbA1c levels are usually less than 6.0 % in people without diabetes. The higher the HbA1C, the greater the chance for developing long-term problems related to diabetes. Medicine Maze

9 Target Blood Sugar Goals ADA Pre-prandial Hours After Meals Under 180 A1c Under 7% AACE Pre-prandial Hours After Meals Under 140 A1c under 6.5% *American Diabetes Association Guidelines *American College of Endocrinologists Guidelines

10 Insulin and Glucagon Regulate Blood Sugar

11 Glucagon (α-cell) Pancreas Insulin (β-cell) Glucose output Liver Blood glucose Glucose uptake Muscle Porte D Jr et al. Clin Invest Med. 1995;18: Adapted with permission from Kahn CR, Saltiel AR. Joslin s Diabetes Mellitus. 14th ed. Lippincott Williams & Wilkins; 2005:

12 Normal Glucose Homeostasis GI tract Pancreas Ingestion of food Release of gut hormones Insulin from β-cells Glucose dependent Glucose uptake by adipose and muscle tissue b-cells a-cells Blood glucose homeostasis Glucagon from α-cells Glucose dependent Glucose production by liver

13 Selected Glucose Regulatory Hormones Insulin Secreted by beta cells of pancreas Decreases glucose blood levels by facilitating glucose entry into o certain cells to be used for energy or energy storage Glucagon Secreted by alpha cells of pancreas Increases glucose blood levels via gluconeogenesis and glycogenolysis in the liver Incretins Gut hormones, release stimulated by food ingestion Glucagon-like like peptide 1 (GLP-1) and gastric inhibitory peptide (GIP) are the predominant incretins Cortisol An essential hormone produced by the adrenal glands Levels rise with stress and lead to an increase in glucose levels Epinephrine Fight or flight hormone produced by the adrenal glands Levels rise with stress and lead to an increase in glucose levels Somatostatin Secreted by the delta cells of the pancreas Inhibits the release of many hormones including insulin, glucagon, and growth hormone

14 Glucoregulatory Role of GLP-1 GLP-1: secreted upon ingestion of food Muscle: Increased glucose uptake ß-cell response β-cells: Enhances glucose- dependent insulin secretion and amylin secretion ß-cell workload Central nervous system: Promotes satiety and reduces appetite α-cells: Suppresses Postprandial glucagon secretion Liver: Reduces hepatic glucose output Stomach: Helps regulate gastric emptying Drucker DJ. Diabetes. 1998;47: ; Flint A et al. J Clin Invest. 1998;101: ; Larsson H et al. Acta Physiol Scand. 1997;160: ; Nauck MA et al. Diabetologia. 1996;39:

15 The Pathophysiology of Type 2 Diabetes Includes Islet Cell Dysfunction and Insulin Resistance

16 Islet cell dysfunction Glucagon (α-cell) * Reduced effect of insulin indicating insulin resistance Pancreas Glucose output Liver Insulin (β-cell) Hyperglycemia * Glucose uptake Muscle 1. Del Prato S, Marchetti P. Horm Metab Res. 2004;36: Porte D Jr, Kahn SE. Clin Invest Med. 1995;18: Adapted with permission from Kahn CR, Saltiel AR. Joslin s Diabetes Mellitus. 14th ed. Lippincott Williams & Wilkins; 2005:

17 100 Progressive Impairment of β-cell Function and Deterioration of Glycemic Control in Type 2 Diabetes β-cell Function Declines Over Time 10 A1C Increases Over Time b-cell function, % β Diet/conv Rx (n=376) Metformin (n=159) SU/intensive (n=511) A1C, % Diet/conv Rx (n=297) Metformin (n=251) SU/intensive (n=695) Years Years Diet/conv Rx=conventional therapy (diet alone); UKPDS=United Kingdom Prospective Diabetes Study; SU/intensive=sulfonylurea or insulin. N=4,209 newly diagnosed patients with type 2 diabetes. Reprinted from UK Prospective Diabetes Study Group 16. Copyright 1995 American Diabetes Association. From Diabetes. 1995;44: Reprinted with permission from The American Diabetes Association.

18 Long-term Complications of Type 2 Diabetes Hyperglycemia Macrovascular Disease Microvascular Disease Damage to medium and large blood vessels Damage to small blood vessels Coronary Artery Disease Cerebrovascular Disease Peripheral vascular disease Retinopathy Nephropathy Neuropathy

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20 Glucagon (α-cell) Pancreas Insulin (β-cell) Glucose output Liver Blood glucose Glucose uptake Muscle Porte D Jr et al. Clin Invest Med. 1995;18: Adapted with permission from Kahn CR, Saltiel AR. Joslin s Diabetes Mellitus. 14th ed. Lippincott Williams & Wilkins; 2005:

21 2. Overview medications and how they work

22 Diabetes treatment before Insulins: Regular NPH Lente Semilente Ultralente Protamine Zinc 1 Class of Oral Agents: 1 st Sulfonylureas 6 pills Generation Tolinase, Diabinese, Orinase, Dymelor 2 nd Generation: Glyburide (Micronase, Diabeta), Glucotrol (Glipizide)

23 Diabetes treatment in 2009 Injectables 8 Insulins: Humalog, Novolog, Apidra, U100 Regular, U500 Regular, NPH, Lantus, Levemir 4 mixtures of insulin: Humulin 70/30, Humalog 75/25, Novolin 70/30, Novolog 70/30 Insulin pens: BD, Lilly NovoNordisk, Sanfo- aventis Insulin pumps: Animas, Medtronic, AccuChek, Omnipod Incretin Mimetic: Byetta Amylinomimetic: Symlin Pancreas Transplant Oral Agents Sulfonylureas: Glimepiride (Amaryl), Glipizide (Glucotrol, Glucotrol XL), Glyburide (Diabetes, Micronase, Glynase) Meglitinides: Prandin (Repaglinide)) and Starlix (Nateglinide) Alpha-glucosidase Inhibitors: Precose (Acarbose)) and Glyset (Miglitol) Biguanides: Glucophage (Metformin), Glucophage XR (Metformin ER, Fortamet, Glutametz) Thiazolidinediones: Actos (pioglitazone)) and Avandia (rosiglitazone) DDP4 Inhibitors: Januvia, Onglyza Combination Oral Agents: Glucovance, Avandamet, Metaglip, Avandaryl, ActoPlusMet, Janumet, Duetact, Prandimet

24 Type 2 Diabetes Medication Options Sulfonylureas Biguanides Alpha-glucosidase inhibitors Thiazolidinediones Meglitinides DPP-4 4 Inhibitors Incretin Mimetics & Synthetic Analogs Insulin

25 Sulfonylureas: Glimepiride (Amaryl), Glipizide (Glucotrol, Glucotrol XL), Glyburide (Diabeta, Micronase, Glynase) Sulfonylureas stimulate beta cells to secrete more insulin Efficacy Reduce A1C by % Side Effects Hypoglycemia Weight gain Generally the least expensive class of medication

26 Biguanides: Metformin; Glucophage; Glucophage XR; Fortamet; Glutametz Biguanides decrease glucose production by the liver and improve insulin s s ability to move sugar into cells, especially muscle cells. Efficacy Decrease fasting plasma glucose mg/dl Reduce A1C % Other Effects Diarrhea and abdominal discomfort (30% of patients) Rarely causes hypoglycemia Lactic acidosis if improperly prescribed No weight gain, with possible modest weight loss Need to be held the day before or day of an IV contrast test Contraindicated in patients with impaired kidney function (Serum Cr > 1.4 mg/dl for women, or 1.5 mg/dl for men)

27 Alpha-glucosidase Inhibitors: Precose (Acarbose), Glyset (Miglitol) Alpha-glucosidase inhibitors block the enzymes that digest starches in the small intestine ( starch( blockers ) Efficacy Decrease peak postprandial glucose mg/dl Decrease A1C % Other Effects Flatulence, diarrhea, nausea or abdominal cramps (70% of patients) Contraindicated in patients with inflammatory bowel disease or cirrhosis

28 Thiazolidinediones (TZD s): Actos (Pioglitazone); Avandia (Rosiglitazone) Thiazolidinediones decrease insulin resistance by making muscle and fat cells more sensitive to insulin. They also suppress hepatic glucose production. Efficacy Reduce A1C ~ % 6 weeks for maximum effect Actos has a better lipid effect Other Effects Weight gain; edema Hypoglycemia (if taken with insulin or agents that stimulate insulin release) Contraindicated in patients with abnormal liver function or CHF Increased risk of bone fractures

29 Meglitinides: Prandin (Repaglinide)) and Starlix (Nateglinide) Meglitinides stimulate insulin secretion (rapidly and for a short duration) in the presence of glucose. Onset of action in min Efficacy Reduce A1C % Other Effects Hypoglycemia; Weight gain Safe at higher levels of serum creatinine than sulfonylureas

30 DDP-4 4 Inhibitors Januvia (Sitagliptin); Onglyza (Saxagliptin) Inhibits dipeptidyl peptidase-4 4 (DPP-4) enzyme - which normally breaks down GLP-1 1 within a few minutes. Increases and prolongs active incretin levels. This in turn increases insulin release and decreases glucagon levels in the circulation in a glucose-dependent manner. A1c lowered 0.6 to 1.0% One pill, once a day, at any time of the day, by mouth, with or without food Weight neutral

31 Byetta: Incretin Mimetic Byetta is a synthetic form of GLP1 that mimics the glucose-lowering lowering actions of glucagon-like like peptide-1 (GLP-1).

32 Brain Byetta Liver Pancreas Beta Cells: Insulin/Amylin Alpha Cells: Glucagon Food (Carbs) Blood Sugar Amylin Insulin In cells for energy Pancreas effect: Stimulates insulin production based on blood glucose Stomach effect: Slows gastric emptying thus reducing the rate at which sugar appears in the bloodstream Liver effect: Decreases liver sugar production after meals by suppressing glucagon secretion from alpha cells Appetite effect: Decreases food intake by enhancing satiety which can lead to weight loss.

33 Brain Pancreas Beta Cells: Insulin/Amylin Alpha Cells: Glucagon Food (Carbs) Liver Blood Sugar Amylin Insulin In cells for energy Stomach effect: Slows gastric emptying thus reducing the rate at which sugar appears in the bloodstream Liver effect: Decreases liver sugar production after meals by suppressing glucagon secretion Appetite effect: Decreases food intake by enhancing satiety which can lead to weight loss.

34 3. Individualize therapy to attain goals

35 Type 2 Diabetes: Oral Medication Use Biguanides: Glucophage, Metformin Sulfonylureas: Amaryl, Glucotrol, Meglitinides:Prandin, Starlix Alpha-glucosidase Inhibitors: Glyset, Precose DPP4: Januvia, Food (Carbs) Onglyza Liver Blood Sugar Combinations: Avandaryl (Avandia, Amaryl) ActosplusMet (Actos, Metformin) Glucovance (Glyburide, Meformin) Avandamet (Avandia, Metformin) Metaglip (Metformin, Glipizide) Duetact: (Actos, Amaryl) Janumet: Januvia, Metformin Prandimet: Prandin, Metformin Pancreas Insulin TZD s: Actos, Avandia In cells for energy

36 Oral Medications & Injections Diabeta, Micronase, Amaryl, Glucotrol, Prandin, Starlix Glyset, Precose Food (Carbs) metformin Liver BYETTA Type 2 s on oral agents Blood Sugar Pancreas Insulin SYMLIN: Type 1 s and 2 s on insulin Actos, Avandia In cells for energy

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38 How to Achieve Normal Blood Sugar Values A1C < 6.5 A1C % Diabetic diet Metformin Metformin + Januvia or Actos Metformin + Byetta + Actos A1C % Metformin + Actos or Glucotrol Metformin + Januvia + Actos Metformin + Byetta + Actos A1C >9.0% Metformin + Januvia + Glucotrol Metformin + Byetta + Actos Metformin or Actos + Insulin + Symlin

39 Glucagon (α-cell) Pancreas Insulin (β-cell) Glucose output Liver Blood glucose Glucose uptake Muscle Porte D Jr et al. Clin Invest Med. 1995;18: Adapted with permission from Kahn CR, Saltiel AR. Joslin s Diabetes Mellitus. 14th ed. Lippincott Williams & Wilkins; 2005:

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42 For more information: Michael R. Ikeler, M.D.