Oral Antidiabetic Drugs: Biguanides and Sulfonylureas

• Oral antidiabetic drugs are used to treat type 2 diabetes.

Biguanides

• Metformin (Glucophage) is a first-line drug for type 2 diabetes.
• It is not used for type 1 diabetes.
• The mechanism of action primarily inhibits hepatic glucose production.
• It also increases the sensitivity of peripheral tissue to insulin.
• It is contraindicated in patients with kidney disease, alcoholism, metabolic acidosis, liver disease, or heart failure.
• Caution is advised with contrast dye due to the risk of lactic acidosis.
• Common adverse effects include abdominal bloating, nausea, cramping, a feeling of fullness, and diarrhea.
• Other adverse effects include a metallic taste, hypoglycemia, and reduced vitamin B12 levels with long-term use.
• Lactic acidosis is a rare but serious complication.

Sulphonylureas

• They are the oldest group of oral antihyperglycemic drugs.
• Second-generation drugs have better potency and fewer adverse effects.
• Examples include gliclazide (Diamicron®), glyburide (Diabeta®), and glimepiride (Amaryl®).
• The mechanism of action stimulates insulin release from β-cells in the pancreas.
• It also decreases glucagon secretion secondarily.
• Functioning β-cells are required, making them most effective in early-stage type 2 diabetes.
• They are not used in type 1 diabetes.
• Hypoglycemia is the most common adverse effect, influenced by dose, eating habits, and liver or kidney function.
• Weight gain is also common due to increased insulin secretion.
• Other adverse effects include skin rash, nausea, epigastric fullness, and heartburn.

Glinides

• Examples include repaglinide (GlucoNorm®), nateglinide (Starlix®).
• It is indicated for type 2 diabetes.
• The mechanism of action increases insulin secretion from the pancreas, similar to sulfonylureas.
• They have a shorter duration of action and should be taken with each meal.

Thiazolidinediones (Glitazones)

• They are the third major drug category.
• The mechanism of action regulates genes involved in glucose and lipid metabolism.
• They enhance insulin sensitivity, decreasing insulin resistance.
• They stimulate peripheral glucose uptake and storage.
• They also inhibit glucose and triglyceride production in the liver.
• They have slow onset of action, with maximal activity taking several months.
• They may preserve β-cell function, slowing the progression of type 2 diabetes.
• They are indicated for type 2 diabetes management.
• They are typically reserved for patients who cannot tolerate or achieve glucose control with metformin or sulfonylureas.
• They are contraindicated in patients with NYHA class III or IV heart failure.
• Caution is advised in patients with liver or kidney disease.
• Common adverse effects include peripheral edema and weight gain due to water retention and increased adipose tissue.
• They are also associated with reduced bone mineral density and increased fracture risk.

Dipeptidyl Peptidase 4 (DPP-4) Inhibitors

• They delay the breakdown of incretin hormones by inhibiting the DPP-4 enzyme.
• Incretin hormones increase insulin synthesis and lower glucagon secretion when plasma glucose is normal or high.
• DPP-4 inhibitors reduce fasting and postprandial glucose concentrations.
• Examples include sitagliptin phosphate monohydrate (Januvia®), alogliptin benzoate (Nesina®), saxagliptin hydrochloride (Onglyza®), and linagliptin (Tradjenta®).
• Sitagliptin phosphate monohydrate (Januvia) was the first approved in Canada.
• The mechanism of action selectively inhibits DPP-4, increasing GLP-1 and GIP concentrations.
• These are not recommended for use during pregnancy.

Sodium Glucose Cotransporter 2 Inhibitors

• They decrease blood glucose by increasing renal glucose excretion.
• They are a new class of oral drugs approved in 2014 for type 2 diabetes.
• Examples include canaglifozin (Invokana®), dapaglifozin (Forxiga®).
• The mechanism of action works independently of insulin.
• They prevent glucose reabsorption from the glomerular filtrate, reducing the renal threshold for glucose and causing glycosuria.
• Commonly reported adverse effects include vaginal yeast infections and urinary tract infections.
• They may increase insulin sensitivity, enhance glucose uptake in muscle cells, and decrease gluconeogenesis.
• They can improve glycemic control, cause weight loss, and have a low risk of hypoglycemia.

Injectable Antidiabetic Drugs: Amylin Agonists

• They mimic the natural hormone amylin.
• They slow gastric emptying.
• They increase satiety.
• They suppress glucagon secretion, reducing hepatic glucose output.
• They are used when other drugs are inadequate.
• Administered via subcutaneous injection.

Injectable Antidiabetic Drugs: Incretin Mimetics

• They mimic incretin hormones.
• They enhance glucose-driven insulin secretion from β-cells.
• They are used only for type 2 diabetes.
• Exenatide is administered via injection pen device.

Injectable Antidiabetic Drugs: Adverse Effects

• Amylin agonists can cause nausea, vomiting, anorexia, and headache.
• Incretin mimetics can cause nausea, vomiting, and diarrhea.
• Rare cases of hemorrhagic or necrotizing pancreatitis have been reported.
• Weight loss may occur.

Hypoglycemia

• Defined as abnormally low blood glucose levels (below 4 mmol/L).
• Mild cases can be managed with dietary changes, increasing protein and decreasing carbohydrates.

Hypoglycemia Symptoms

• Adrenergic symptoms include anxiety, tremors, hunger, palpitations, and sweating.
• Central nervous system symptoms include difficulty concentrating, confusion, weakness, drowsiness, vision changes, difficulty speaking, dizziness, and headache.
• Later signs include hypothermia and seizures.
• If untreated, it can lead to coma and death.

Glucose-Elevating Drugs

• Oral forms of concentrated glucose are available as gels, liquids, or tablets.
• 50% dextrose in water (D50W) can be administered.
• Glucagon can also be used.

Nursing Implications

• Thorough patient history, vital signs, blood glucose levels, HbA1c, potential complications, and drug interactions should be documented.
• Assess the patient’s ability to consume food and check for nausea or vomiting.
• Hypoglycemia may occur if antidiabetic drugs are given without food intake.
• Consult with the primary care provider regarding antidiabetic drug therapy if the patient is NPO for a test or procedure.
• Overall concerns for diabetic patients increase under stress, during pregnancy or lactation, with infection, or with illness or trauma.
• Thorough patient education is essential regarding the disease process, diet and exercise recommendations, self-administration of drugs, and potential complications.

Insulin-Specific Nursing Implications

• Ensure the correct drug, route, type of insulin, and dosage.
• Insulin orders and prepared dosages are second-checked with another registered nurse.
• Check blood glucose levels before administration.
• To mix suspensions, roll vials between hands instead of shaking.
• Ensure correct storage of insulin vials.
• Only use insulin syringes for measurement and administration.
• Ensure correct timing of the insulin dose with meals.
• When mixing two types of insulin in one syringe, withdraw the regular or rapid-acting (clear) insulin first.
• Provide thorough education regarding self-administration, including timing of doses, blood glucose monitoring, and injection site rotation.

Oral Antidiabetic Drug Nursing Implications

• Always check blood glucose levels before administration.
• Administer usually 30 minutes before meals, except for α-Glucosidase inhibitors which are given with the first bite of each main meal.
• Metformin is taken with meals to reduce gastrointestinal effects.
• Metformin should be discontinued prior to studies with contrast dye due to potential renal effects.

Hypoglycemia Management: Nursing Implications

• Assess for signs of hypoglycemia.
• If the patient is conscious, administer oral glucose in the form of tablets, liquid, gel, corn syrup, honey, fruit juice, or a small snack.
• If the patient is unconscious, administer D50W IV or glucagon.
• Monitor blood glucose levels.

Monitoring Therapeutic Response

• Monitor for a decrease in blood glucose levels to the prescribed level.
• Measure HbA1c to monitor long-term compliance.
• Watch for and monitor both hypoglycemia and hyperglycemia.