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Drug Therapy for Diabetes

Chapter 20: Drug Therapy for Diabetes

Page 1: Overview of the Pancreas

  • The pancreas is located behind the stomach and serves as both an exocrine and endocrine gland.

  • It produces two critical hormones for glucose homeostasis:

    • Insulin

    • Glucagon

  • Glycogen is the form in which excess glucose is stored in the liver and skeletal muscle tissue.

  • Glycogenolysis is the process of converting glycogen into glucose when needed.

Page 2: Insulin Functions

  • Insulin has a direct effect on fat metabolism, including:

    • Stimulating lipogenesis (the formation of fat)

    • Inhibiting lipolysis (the breakdown of fat)

    • Stimulating protein synthesis

    • Promoting intracellular shift of potassium and magnesium into the cells.

  • Cortisol, epinephrine, and growth hormone synergize with glucagon to counter the effects of insulin.

Page 3: Overview of Diabetes Mellitus

  • Diabetes Mellitus (DM) is a group of progressive diseases, often regarded as a syndrome rather than a single disease.

  • There are two primary types of diabetes:

    • Type 1 Diabetes Mellitus

    • Type 2 Diabetes Mellitus

Page 4: Signs and Symptoms of Diabetes Mellitus

  • The following signs and symptoms indicate the presence of diabetes:

    • Elevated fasting blood glucose (criteria: higher than 126 mg/dL)

    • Hemoglobin A1C (HbA1C) level greater than or equal to 6.5%

    • Polyuria (frequent urination)

    • Polydipsia (increased thirst)

    • Polyphagia (increased hunger)

    • Glycosuria (glucose in urine)

    • Unexplained weight loss

    • Fatigue

    • Blurred vision

Page 5: Type 1 Diabetes Mellitus

  • Characterized by a lack of insulin production or the production of defective insulin.

  • Affected patients require exogenous insulin.

  • Fewer than 10% of all DM cases are Type 1.

  • Complications of Type 1 DM include:

    • Diabetic Ketoacidosis (DKA)

Page 6: Diabetic Ketoacidosis (DKA)

  • DKA is defined by several criteria:

    • Hyperglycemia (elevated blood glucose levels)

    • Presence of ketones in the serum i

    • Acidosis (metabolic acidosis)

    • Dehydration

    • Electrolyte imbalances

  • Approximately 25% to 30% of patients newly diagnosed with Type 1 DM present with DKA.

Page 7: Type 2 Diabetes Mellitus

  • Type 2 Diabetes Mellitus is the most common type, accounting for 90% of all cases.

  • It is caused by a combination of insulin deficiency and insulin resistance.

  • Insulin l

  • Microalbuminemia (protein in urine)

  • An increased risk for thrombotic events (blood clotting events).

  • These comorbid conditions are collectively termed metabolic syndrome, also known as insulin-resistance syndrome or syndrome X.

Page 9: Gestational Diabetes

  • Gestational diabetes is characterized by hyperglycemia during pregnancy.

  • Insulin must be administered during pregnancy to prevent birth defects.

  • The condition often subsides after delivery, but 30% of patients may develop Type 2 DM within 10 to 15 years after pregnancy.

Page 10: Non-Pharmacologic Treatment Interventions

  • Treatment for diabetes includes non-pharmacologic strategies such as:

    • For Type 1 DM: Always requires insulin therapy.

    • For Type 2 DM: Encouragement of weight loss, improving dietary habits, smoking cessation, reduced alcohol consumption, and regular physical exercise.

Page 11: Treatment for Diabetes

  • Treatments for diabetes can be categorized as follows:

    • Type 1 DM: Insulin therapy is mandatory.

    • Type 2 DM:

    • Lifestyle changes

    • Oral drug therapy

    • Insulin is introduced when other measures do not provide adequate glycemic control.

Page 12: Types of Antidiabetic Drugs

  • There are various classes of antidiabetic drugs:

    • Insulins

    • Oral hypoglycemic drugs

    • New injectable hypoglycemic drugs that may be used in conjunction with insulin or antidiabetic medications.

Page 13: Insulin Functions and Goals

  • Insulin acts as a substitute for the endogenous hormone, creating effects similar to natural insulin by restoring the diabetic patient's capability to:

    • Metabolize carbohydrates, fats, and proteins

    • Store glucose in the liver

    • Convert glycogen to fat stores.

Page 14: Human Insulin

  • Human insulin is derived using recombinant DNA technologies, produced by bacteria and yeast.

  • The principal goal of insulin therapy is to achieve tight glucose control to minimize the risk of long-term complications.

Page 15: Rapid-Acting Insulin

  • Rapid-acting insulins for treating Type 1 and Type 2 DM include:

    • Insulin lispro (Humalog): Similar in action to endogenous insulin;

    • Insulin aspart (NovoLog);

    • Insulin glulisine (Apidra).

  • Characteristics of rapid-acting insulins:

    • Fastest onset (5 to 15 minutes)

    • Peak effect occurs within 1 to 2 hours

    • Duration of action is 3 to 5 hours

    • Patient must consume a meal shortly after administration.

    • Can be administered subcutaneously or via continuous subcutaneous infusion but not intravenously.

Page 16: Afrezza

  • Afrezza is a rapid-acting insulin administered via inhalation.

  • Characteristics include:

    • Peak action within 12 to 15 minutes

    • Duration of action of 2 to 3 hours

    • Administered within 20 minutes of a meal.

    • Must be used in conjunction with long-acting insulins or oral diabetic agents for Type 2 DM.

  • Side effects may include hypoglycemia, cough, and throat pain, and it is contraindicated in smokers and individuals with chronic lung diseases due to a black box warning regarding acute bronchospasm.

Page 17: Short-Acting Insulin

  • Regular insulin (Humulin R) is the main short-acting insulin.

  • Routes of administration include:

    • IV bolus, IV infusion, intramuscular (IM), or subcutaneous (SQ).

  • Characteristics when administered via SQ route:

    • Onset: 30 to 60 minutes

    • Peak: 2.5 hours

    • Duration: 6 to 10 hours

Page 18: Insulin Concentrations

  • Insulin is available in several concentrations:

    • U100: Standard concentration for most patients (100 units/mL)

    • U200: Concentration for insulin pens

    • U300: Higher concentration for insulin pens

    • U500: Newer concentration intended for patients requiring very high doses (500 units/mL)

Page 19: Intermediate-Acting Insulin

  • Insulin isophane suspension (NPH) has a cloudy appearance and is often combined with regular insulin.

  • Characteristics include:

    • Onset: 1 to 2 hours

    • Peak: 4 to 8 hours

    • Duration: 10 to 18 hours

Page 20: Long-Acting Insulin

  • Long-acting insulins include:

    • Insulin glargine (Lantus):

    • Clear, colorless solution with a constant level of insulin in the blood

    • Usually dosed once daily or every 12 hours

    • Classified as basal insulin

    • Onset: 1 to 2 hours

    • Peak: none

    • Duration: 24 hours

    • Toujeo: Concentrated U-300 formulation.

Page 21: Long-Acting Insulin (Cont.)

  • Other long-acting insulins:

    • Insulin detemir (Levemir): Duration is dose-dependent, requiring twice-daily doses for lower doses and once daily for higher doses.

    • Insulin glargine (Basaglar): A biosimilar insulin available in U100 form.

    • Insulin degludec (Tresiba): An ultra-long-acting insulin, administered once daily, available in U100 or U200 forms.

Page 22: Fixed-Combination Insulins

  • Fixed combinations include:

    • Humulin 70/30,

    • Humulin 50/50,

    • Novolin 70/30,

    • Humalog Mix 75/25,

    • Humalog 50/50,

    • NovoLog 70/30.

  • Each combination includes two different insulins, with one being intermediate-acting and the other being either a rapid-acting or short-acting type.

Page 23: Sliding-Scale Insulin Dosing

  • Sliding-scale insulin dosing involves:

    • Use of SQ rapid-acting (lispro or aspart) or short-acting (regular) insulins adjusted based on blood glucose test results.

    • Typically utilized in hospitalized diabetic patients or those on total parenteral nutrition or enteral tube feedings.

    • Insulin ordered increases as blood glucose rises. A primary disadvantage is the delay of insulin administration until after hyperglycemia occurs, leading to marked fluctuations in glucose control.

Page 24: Basal-Bolus Insulin Dosing

  • This method is the preferred treatment for hospitalized patients with DM and mimics a healthy pancreas by delivering basal insulin constantly and also provides bolus doses as needed.

  • Basal insulin typically consists of a long-acting insulin (e.g., insulin glargine), while bolus insulin comprises fast-acting insulins (insulin lispro or insulin aspart).

Page 25: Oral Antidiabetic Drugs

  • Treatment for Type 2 DM is effective when involving several components:

    • Careful monitoring of blood glucose levels

    • Therapy with one or more oral drugs

    • Treatment of associated comorbid conditions such as high cholesterol and hypertension.

Page 26: New-Onset Type 2 DM Treatment (American Diabetes Association Guidelines 2013)

  • The approach includes:

    • Lifestyle interventions

    • Administration of the oral biguanide drug metformin.

    • If lifestyle modifications and maximum tolerated metformin doses do not achieve HbA1C goals after 3 to 6 months, a second oral agent (GLP-1 agonist like liraglutide, exenatide, albiglutide, or lixisenatide) or insulin should be introduced.

Page 27: Metformin

  • Metformin (Glucophage) is the first-line oral medication and most commonly prescribed for Type 2 DM.

  • It is not used for Type 1 DM.

Page 28: Mechanism of Action for Biguanides

  • The effects of biguanides, particularly metformin, include:

    • Decrease in glucose production by the liver

    • Reduction of intestinal absorption of glucose

    • Increase in glucose uptake by tissues

    • Does not lead to increased insulin secretion from the pancreas, thus it does not cause hypoglycemia.

Page 29: Adverse Effects of Biguanides

  • Common side effects associated with biguanide use (metformin) include:

    • Primarily affecting the gastrointestinal (GI) tract:

    • Abdominal bloating

    • Nausea

    • Cramps

    • Diarrhea

    • Feeling of fullness.

    • Some additional effects:

    • Metallic taste

    • Reduced vitamin B12 levels

    • Lactic acidosis, a rare but potentially lethal condition.

  • Biguanides do not cause hypoglycemia.

Page 30: Sulfonylureas

  • Second-generation sulfonylureas include:

    • Glimepiride (Amaryl)

    • Glipizide (Glucotrol)

    • Glyburide (DiaBeta).

  • These drugs stimulate insulin secretion from the pancreas's beta cells, increasing insulin levels after confirming that beta cell function remains active.

  • Additionally, they improve tissue sensitivity to insulin, resulting in lower blood glucose levels.

  • Common adverse effects include:

    • Hypoglycemia

    • Hematologic effects (related to blood)

    • Nausea

    • Epigastric fullness

    • Heartburn

    • (and several others).

Page 31: Glinides

  • Glinides include:

    • Repaglinide (Prandin)

    • Nateglinide (Starlix).

  • Indicated for Type 2 DM, they share similar actions to sulfonylureas by increasing insulin secretion from the pancreas.

Page 32: Glinides Adverse Effects

  • Adverse effects of glinides include:

    • Headache

    • Dizziness

    • Hypoglycemic effects

    • Weight gain

    • Joint pain

    • Symptoms similar to upper respiratory infections or flu-like symptoms.

Page 33: Thiazolidinediones (Glitazones)

  • Key examples:

    • Pioglitazone (Actos)

    • Rosiglitazone (Avandia) (available only through specialized manufacturer programs).

  • These drugs act as insulin-sensitizing agents, with indications for Type 2 DM. Their mechanism includes:

    • Decreasing insulin resistance

    • Increasing glucose uptake and usage in skeletal muscles

    • Inhibiting glucose and triglyceride production in the liver.

Page 34: Adverse Effects of Thiazolidinediones

  • Side effects may include:

    • Weight gain

    • Fluid retention

    • Adverse cardiovascular effects in specific populations.

Page 35: Alpha-Glucosidase Inhibitors

  • Examples include:

    • Acarbose (Precose)

    • Miglitol (Glyset).

  • Indicated for Type 2 DM, these drugs work by:

    • Reversibly inhibiting the enzyme alpha-glucosidase in the small intestine, which leads to delayed absorption of carbohydrates.

  • Adverse effects include:

    • Flatulence

    • Diarrhea

    • Abdominal pain.

  • They do not cause hypoglycemia, hyperinsulinemia, or weight gain.

Page 36: Alpha-Glucosidase Inhibitors Mechanism of Action

  • Alpha-glucosidase inhibitors must be taken with meals to prevent excessive postprandial (after-meal) blood glucose elevations. Their efficacy requires administration with the first bite of each meal.

Page 37: Dipeptidyl Peptidase-IV (DPP-IV) Inhibitors

  • DPP-IV inhibitors (gliptins) include the following:

    • Sitagliptin (Januvia)

    • Saxagliptin (Onglyza)

    • Linagliptin (Tradjenta)

    • Alogliptin (Nesina).

Page 38: DPP-IV Inhibitors Mechanism of Action

  • These drugs delay the breakdown of incretin hormones by inhibiting the DPP-IV enzyme. Incretin hormones are important as they:

    • Increase insulin synthesis

    • Lower glucagon secretion

    • Reduce fasting and postprandial glucose concentrations.

Page 39: DPP-IV Inhibitors Adverse Effects

  • Common adverse effects include:

    • Upper respiratory tract infections

    • Headache

    • Diarrhea

    • Hypoglycemia can occur, particularly when used alongside sulfonylureas.

Page 40: Injectable Antidiabetic Drugs

  • Types of injectable drugs include:

    • Amylin agonist: Pramlintide (Symlin).

    • Incretin mimetics: Include drugs like Exenatide (Byetta), Dulaglutide (Trulicity), Liraglutide (Victoza), Albiglutide (Tanzeum), and Lixisenatide (Adlyxin).

    • Combo agents include Soliqua (insulin glargine and lixisenatide) and Xultophy (insulin degludec and liraglutide).

Page 41: Mechanism of Action for Amylin Agonist

  • The mechanism of the amylin agonist (Pramlintide) includes:

    • Mimics the natural hormone amylin

    • Slowing gastric emptying

    • Suppressing glucagon secretion, resulting in reduced liver glucose output

    • Modulates appetite and satiety from a central perspective.

  • Used for patients unable to achieve adequate glucose control with other medications.

Page 42: Incretin Mimetics Mechanism of Action

  • The incretin mimetics enhance glucose-driven insulin secretion from the beta cells of the pancreas and are only used for Type 2 DM. For instance, Exenatide is provided via an injection pen device.

Page 43: Adverse Effects of Injectable Antidiabetic Drugs

  • Common adverse effects include:

    • Nausea

    • Vomiting

    • Diarrhea

    • In rare cases, drugs may lead to hemorrhagic or necrotizing pancreatitis.

    • Notable weight loss associated with the use of specific agents.

Page 44: Sodium-Glucose Cotransporter 2 (SGLT2) Inhibitors

  • SGLT2 inhibitors are a newer class of oral medications for treating Type 2 DM and include:

    • Canagliflozin (Invokana)

    • Dapagliflozin (Farxiga)

    • Empagliflozin (Jardiance).

  • Their action involves:

    • Inhibition of the SGLT2, which leads to decreased blood glucose by promoting renal glucose excretion.

    • Works independently of insulin, thus decreasing glucose reabsorption from the glomerular filtrate and ultimately reducing renal threshold for glucose leading to glycosuria.

Page 45: SGLT2 Inhibitors Additional Benefits

  • Additional effects of SGLT2 inhibitors include:

    • Increased insulin sensitivity and glucose uptake in muscle cells

    • Decreased gluconeogenesis

  • These medications result in improved glycemic control, weight loss, and a low risk of hypoglycemia.

Page 46: Understanding Hypoglycemia

  • Hypoglycemia is defined as an abnormally low blood glucose level (below 50 mg/dL).

  • Mild cases might be treated with dietary adjustments — increasing protein and reducing carbohydrates to avoid rebound postprandial hypoglycemia.

Page 47: Symptoms of Hypoglycemia

  • Symptoms may present in two phases:

    • Early symptoms (e.g., confusion, irritability, tremor, sweating)

    • Late symptoms (including hypothermia, seizures; coma and death are possible without treatment).

Page 48: Glucose-Elevating Drugs

  • Treatments to counter hypoglycemia include:

    • Oral forms of concentrated glucose: Buccal tablets, semisolid gel

    • 50% dextrose in water (D50W)

    • Glucagon.

Page 49: Nursing Implications before Drug Administration

  • Prior to administering drugs that affect glucose levels, ensure the following:

    • A thorough patient history

    • Vital signs assessment

    • Blood glucose and HbA1C level check

    • Evaluate potential complications and drug interactions.

Page 50: Assessing Patient Condition for Drug Administration

  • Check:

    • Patient's ability to consume food.

    • Presence of nausea or vomiting. Hypoglycemia may develop if antidiabetic drugs are administered without food intake.

    • If the patient is NPO (nothing by mouth) for a procedure, clarify with the primary care provider orders for antidiabetic drug therapy.

Page 51: Considerations Under Specific Conditions

  • Overall concerns for patients with DM increase when they are experiencing:

    • Stress

    • Infection

    • Illness or trauma

    • Pregnancy or lactation.

Page 52: Patient Education

  • Thorough patient education is critical, covering:

    • The disease process

    • Recommended diet and exercise

    • Self-administration of insulin or oral medications

    • Awareness of potential complications.

Page 53: Ensuring Proper Insulin Administration

  • When insulin is prescribed, ensure verification of:

    • Correct route of administration

    • Correct type of insulin

    • Timely dosage delivery

    • Correct dosage.

  • Insulin orders and prepared doses should be second-checked with another nurse.

Page 54: Blood Glucose Monitoring

  • Before administering insulin:

    • Check blood glucose levels.

    • Roll vials between hands instead of shaking to mix suspensions.

    • Verify correct storage of insulin vials.

    • Use only insulin syringes (calibrated in units) for measurement and administration.

    • Ensure timely timing of insulin doses aligned with meals.

Page 55: Drawing Up Insulin

  • When drawing two types of insulin into one syringe, always withdraw the regular or rapid-acting insulin first.

  • Provide extensive education for patients regarding self-administration, including injection timing, blood glucose monitoring, and injection site rotation.

Page 56: Oral Antidiabetic Drug Administration

  • Always check blood glucose levels before administering oral diabetic medications.

  • Typically administered 30 minutes before meals, except for alpha-glucosidase inhibitors, which are given with the first bite of each main meal.

  • Metformin should be taken with meals to minimize gastrointestinal side effects and should be discontinued if the patient is to undergo imaging studies involving contrast dye due to potential renal effects; consult with the prescriber.

Page 57: Signs of Hypoglycemia and Emergency Protocol

  • Assess for signs of hypoglycemia. If it occurs:

    • Administer oral glucose if the patient is conscious (e.g., glucose tablets, gel, syrup, honey, fruit juice, nondiet soda, or light snacks).

    • If unconscious, deliver D50W or glucagon IV and monitor blood glucose levels.

Page 58: Monitoring for Therapeutic Response

  • Monitor:

    • Decrease in blood glucose levels to the prescribed targets by the physician.

    • HbA1C levels for long-term compliance with diet and medication regimens.

    • Signs of hypoglycemia and hyperglycemia.

Page 59: Summary of Nursing Implications

  • Nursing implications must include careful assessment, intervention, and education regarding diabetes management, including both pharmacologic and non-pharmacologic strategies for maintaining optimal glucose levels and preventing complications. Proper monitoring of therapeutic responses to undertaken treatments is essential for effective diabetes management.

Page 60: Conclusion

  • A successful management program for diabetes integrates individual lifestyle adaptations with pharmacologic therapies while ensuring patient understanding and self-efficacy in handling their condition. Keeping abreast of advancements in diabetes treatment allows for better care outcomes and quality of life for those affected.

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