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Comprehensive Guide to Diabetic
Medications
Diabetic Medications
Type 1 Diabetes
Lack of insulin production or production of defective insulin Affected patients need exogenous insulin Fewer than 10% of all cases are type 1 Complications: Diabetic ketoacidosis (DKA) Hyperosmolar hyperglycemic state (HHS) Most common cause of DKA or HHS is stress Pancreas is an exocrine and endocrine gland that produces insulin and glucagon Produce little or no endogenous insulin When blood glucose levels are high and there is no insulin to allow glucose to be used, the body begins breaking down fatty acids for fuel
Type 2 Diabetes
Most common type, accounting for 90% of cases Caused by insulin deficiency and insulin resistance Many tissues are resistant to insulin due to reduced number or responsiveness of insulin receptors Usually caused by obesity, coronary artery disease, dyslipidemia, and hypertension Increased risk for thrombolytic events Post-prandial glucose: sugar test after a meal
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 diabetes within 10-15 years If someone is diabetic before pregnancy, it does not switch to gestational hyperglycemia
Symptoms
3 P's: polyuria, polyphagia, and polydipsia Glucosuria Unintentional weight loss Fatigue Symptoms worsen with stress and illness
Complications
Heart disease related to coronary artery damage Peripheral vascular disease, including neuropathy, ulcers, and amputation Renal disease (nephropathy) evidenced by proteinuria Retinal disease (retinopathy) and blindness Ketosis and DKA in type 1 DM
Treatment Goals
Treat diabetes aggressively to decrease vascular complications later Normalize and stabilize blood sugar Target A1C of ≤ 7% (adjusted for age and baseline A1C) Treat as aggressively as possible/tolerable, as soon as possible, to prevent complications (legacy effect)
Type 1 Treatment
Insulin therapy
Type 2 Treatment
Often begins with lifestyle modification (exercise, dietary changes, weight loss) Oral hypoglycemics are then added as mono, dual, or triple therapy Cannot solely increase due to kidney and liver issues Insulin may also be used solely or in combination with some oral agents
Types of Antidiabetic Drugs
Insulins Oral hypoglycemic drugs Combination of oral hypoglycemics and insulin
Insulins
Function as a substitute for the endogenous hormone Effects are the same as those of normal endogenous insulin Restores the diabetic patient's ability to metabolize carbohydrates, fats, and proteins, store glucose in the liver, and convert glycogen to fat stores
Rapid-Acting Insulins
Insulin lispro (Humalog) and insulin aspart (NovoRapid) Most rapid onset of action (10-15 minutes) Peak: 1-2 hours, need to eat after injection or take with first bite of food Duration: 3-5 hours Patient must eat a meal after injection
Effective treatment involves lifestyle changes, careful monitoring of blood glucose levels, therapy with one or more drugs, and treatment of associated comorbid conditions
Biguanide - Metformin (Glucophage)
First-line drug and only drug in this class Most commonly used oral medication for type 2 diabetes Especially good for patients with a BMI over 25 Contraindicated in liver and kidney disease Adverse effects: abdominal bloating, nausea, cramping, feeling full, diarrhea and weight loss, metallic taste, hypoglycemia (least compared to other drugs), and a reduction in vitamin B12 levels after long-term use Lactic acidosis is an extremely rare complication
Sulphonylureas
Mechanism of action: stimulates release of insulin and increases sensitivity of receptors Bind to specific receptors on the beta cells in the pancreas to stimulate release of insulin Patients need to still have functioning beta cells in the pancreas Second generation: glimepiride (Amaryl), gliclazide (Diamicron), glyburide (DiaBeta) Adverse effects: most common is hypoglycemia, also include weight gain and GI distress Do not take alcohol, as it causes hepatotoxicity, flushing, and palpitations
Glinides
Indications: type 2 diabetes Mechanism of action: similar to sulfonylureas but shorter duration of action and must be given with each meal Adverse effects: hypoglycemia is most common, especially if not taken with food, may cause weight gain Example: repaglinide (GlucoNorm)
Thiazolidinediones (Glitazones)
Never lead with this med, comes after metformin and sulphonylureas Mechanism of action: decrease insulin resistance/inhibit gluconeogenesis by regulating genes involved in glucose and lipid metabolism May take 3-4 months for onset Adverse effects: fluid retention, headache, weight gain Contraindicated in heart failure or pulmonary edema (related to fluid retention) Examples: pioglitazone (Actos), rosiglitazone (Avandia)
α-Glucosidase Inhibitors
Mechanism of action: act by delaying glucose digestion, AKA "starch blockers" and can therefore prevent post-prandial glucose spike Adverse effects: minor GI adverse effects such as flatulence Monitor for hypoglycemia when used with glyburide or insulin Less commonly used, usually taken in combination with other oral hypoglycemics Must take with food Example: acarbose (Glucobay)
Sodium-Glucose Cotransporter 2 (SGLT2) Inhibitors
Mechanism of action: inhibit glucose reabsorption in the proximal renal tubules, resulting in glucosuria May increase insulin sensitivity and glucose uptake in muscle cells and decrease gluconeogenesis Causes better glycemic control with less fluctuation of blood sugar Example: canagliflozin (Invokana) Not for patients with type 1, kidney disease, or who have been treated for DKA
Injectable Antidiabetic Drugs
Incretins are hormones released by the GI tract in response to food Incretin mimetics: Mechanism of action: enhance glucose-dependent insulin secretion, suppress elevated glucagon secretion, and slow gastric emptying Examples: exenatide (Byetta) and liraglutide (Victoza) Often used for failed type 2 diabetics where oral therapy isn't working Cannot be used for kidney failure or kidney disease
Liraglutide (Victoza)
Mechanism of action: increase insulin secretion, delay gastric emptying (weight loss), potential to regenerate beta cells, promote insulin sensitivity Lowers triglycerides, good for hyperlipidemia Adverse effects: moderate transient GI side effects Can be combined with insulin and some oral anti-diabetic agents Daily SC injection, slow upward titration most successful Black box warning: risk for thyroid medullary cancer
Incretin Mimetics Adverse Effects
Nausea, vomiting, and diarrhea, and weight loss Rare cases of hemorrhagic or necrotizing pancreatitis
Hypoglycemia
Abnormally low blood glucose level, below 4 mmol/L
