Antidiabetic Drugs Diabetes Mellitus Diabetes mellitus DM actually is not a single disease but a group of progressive diseases It is often regarded as a syndrome rather than a disease Two types o Type 1 Fewer in number o Type 2 Signs and symptoms o Elevated fasting blood glucose higher than 126 mg dL or a hemoglobin A1C A1C level greater than or equal to 6 5 A1C normal differs with different lab values o Polyuria o Polydipsia o Polyphagia o Glycosuria o Unexplained weight loss only type 1 o Fatigue o Blurred vision elevated blood sugar Type 1 Diabetes Mellitus Lack of insulin production or production of defective insulin Affected patients need exogenous insulin Fewer than 10 of all diabetes cases are type 1 Complications o Diabetic ketoacidosis DKA o Hyperosmolar nonketotic syndrome o Emergency situations o Must worry about low blood sugar Type 2 Diabetes Mellitus Most common type 90 of all cases Caused by insulin deficiency and insulin resistance Many tissues are resistant to insulin o Reduced number of insulin receptors o Insulin receptors less responsive Several comorbid conditions o Obesity o Coronary heart disease o Dyslipidemia o Hypertension o Microalbuminemia protein in the urine o Increased risk for thrombotic blood clotting events o Tend to be sedentary These comorbidities are collectively referred to as metabolic syndrome or insulin resistance syndrome or syndrome X Gestational Diabetes Hyperglycemia that develops during pregnancy Insulin must be given to prevent birth defects Usually subsides after delivery 30 of patients may develop Type 2 DM within 10 to 15 years Major Long Term Complications of DM Both Types Macrovascular atherosclerotic plaque o Coronary arteries o Cerebral arteries o Peripheral vessels Microvascular capillary damage o Retinopathy blindness o Neuropathy Loss of sensation in the feet Can have pain with this o Nephropathy Kidney failure Screening for DM Prediabetes o Categories of increased risk for diabetes Hemoglobin A1C of 5 7 to 6 4 Fasting plasma glucose FPG levels higher than or equal to 100 mg dL but less than 126 mg dL Impaired glucose tolerance test oral glucose challenge Valuable in early pregnancy Screening recommended every 3 years for all patients 45 years and older Treatment for DM Type 1 o Insulin therapy Type 2 o Lifestyle changes o Oral drug therapy o Insulin when the above no longer provide glycemic control Types of Antidiabetic Drugs Insulins Oral hypoglycemic drugs o Both aim to produce normal blood glucose states Some new injectable hypoglycemic drugs may be used in addition to insulin or antidiabetic drugs Insulins Has to be injected Function as a substitute for the endogenous hormone Effects are the same as normal endogenous insulin o Weight gain Restores the diabetic patient s ability to o Metabolize carbohydrates fats and proteins o Store glucose in the liver o Convert glycogen to fat stores Human insulin o Derived using recombinant DNA technologies o Recombinant insulin produced by bacteria and yeast Goal tight glucose control o To reduce the incidence of long term complications Rapid acting o Most rapid onset of action 5 to 15 minutes o Shorter duration o Patient must eat a meal after injection o Insulin lispro Humalog Similar action to endogenous insulin o Insulin aspart NovoLog o Insulin glulisine Apidra o May be given subcutaneously or via continuous subcutaneous infusion pump but not IV Short acting o Regular insulin Humulin R o Onset 30 to 60 minutes The only insulin product that can be given by IV bolus IV infusion or even IM Intermediate acting o Insulin isophane suspension also called NPH Cloudy appearance Slower in onset and more prolonged in duration than endogenous insulin Long acting o glargine Lantus detemir Levemir Clear colorless solution Usually dosed once daily Referred to as basal insulin Works in young population Fixed combinations o Humulin 70 30 o Humulin 50 50 o Novolin 70 30 o Humalog Mix 75 25 o Humalog 50 50 o NovoLog 70 30 Insulin use in special populations o Pediatrics Insulin pumps are preferable o Pregnant women Insulin therapy Can be difficult to teach pt s Need to know that they can live normal healthy lives Just because they have it doesn t mean their children will have it Sliding Scale Insulin Dosing Subcutaneous short acting or regular insulin doses adjusted according to blood glucose test results Typically used in hospitalized diabetic patients or those on total parenteral nutrition TPN or enteral tube feedings o GLUCOCORTICOSTERIODS STERIODS INCREASE THE BLOOD SUGAR Subcutaneous insulin is ordered in an amount that increases as the blood glucose increases Disadvantage delays insulin administration until hyperglycemia occurs results in large swings in glucose control Basal Bolus Insulin Dosing Preferred method of treatment for hospitalized diabetic patients Mimics a healthy pancreas by delivering basal insulin constantly as a basal and then as needed as a bolus Basal insulin is a long acting insulin insulin glargine Bolus insulin insulin lispro or insulin aspart Oral Antidiabetic Drugs Used for type 2 diabetes Treatment for type 2 diabetes includes lifestyle modifications o Diet exercise smoking cessation weight loss Oral antidiabetic drugs may not be effective unless the patient also makes behavioral or lifestyle changes Biguanides The best o metformin Glucophage o Start patients on this drug first o If we have to add another medication it will be a sulfonylurea Sulfonylureas o Second generation glimepiride Amaryl glipizide Glucotrol glyburide DiaBeta Micronase o Don t give this to pt allergic to sufonamides o Know the drug class Dipeptidyl peptidase IV DPP IV inhibitors o sitagliptin Januvia o saxagliptin Onglyza o linagliptin Tradjenta New class complex Mechanism of Action o Biguanides Decrease production of glucose by the liver Decrease intestinal absorption of glucose Increase uptake of glucose by tissues Do not increase insulin secretion from the pancreas does not cause hypoglycemia Also causes weight loss o Sulfonylureas Stimulate insulin secretion from the beta cells of the pancreas thus increasing insulin levels Decreases absorption of glucose Beta cell function must be present Improve sensitivity to insulin in tissues Result in lower blood glucose levels o Dipeptidyl peptidase IV DPP IV inhibitors Delay breakdown of incretin hormones by inhibiting the enzyme DPP IV Incretin hormones increase insulin synthesis and lower glucagon secretion Reduce fasting and postprandial glucose