Name of the Oral Antidiabetic drugs
- Metformin
- Pioglitazone
1.Metformin
| Metformin |
| Availability Oral solution: 100 mg/ml, 500 mg/5 ml Tablets: 500 mg, 850 mg, 1,000 mg Tablets (extended release): 500 mg, 750 mg |
| Indications and dosages ➣ Adjunct to diet and exercise to improve glycemic control in type 2 (non-insulin-dependent) diabetes mellitus Adults and children ages 17 and older: Initially, 500 mg P.O. b.i.d.; may increase by 500 mg/week, up to 2,000 mg/day. If patient needs more than 2,000 mg/day, give in three divided doses (not to exceed 2,500 mg/day). Alternatively, 850 mg P.O. daily, increased by 850 mg q 2 weeks, up to 2,550 mg/day in divided doses (850 mg t.i.d.). Extended-release tablets—500 mg/day P.O. with evening meal; may increase by 500 mg weekly, up to 2,000 mg/day. If 2,000 mg once daily is inadequate, 1,000 mg may be given b.i.d. Children ages 10 to 16: 500 mg P.O. b.i.d. Increase in increments of 500 mg weekly to a maximum of 2,000 mg daily in divided doses. ➣ Concurrent use with sulfonylurea or insulin in type 2 diabetes mellitus Adults and children ages 17 and older: If patient hasn’t responded to maximum metformin dosage of 2,000 mg/ day in 4 weeks, sulfonylurea may be added while metformin therapy continues at highest dosage (even if patient experienced primary or secondary failure on sulfonylurea). Adjust dosages of both drugs until glycemic control adequate. If response inadequate within 1 to 3 months of concurrent therapy, consider alternatives. ➣ Concurrent use with insulin in type 2 diabetes mellitus Adults ages 17 and older: Continue current insulin dosage while starting metformin at 500 mg P.O. once daily. If response inadequate, increase metformin dosage by 500 mg after approximately 1 week and then by 500 mg weekly until glycemic control is achieved. Maximum metformin dosage is 2,500 mg. Optimally, decrease insulin dosage 10% to 25% when fasting plasma glucose level is below 120 mg/dl. Individualize dosage adjustments based on glycemic response. |
Mechanism of Action
May promote storage of excess glucose as glycogen in the liver, which reduces glucose production. Metformin also may improve glucose use by skeletal muscle and adipose tissue by increasing glucose transport across cell membranes. This drug also may increase the number of insulin receptors on cell membranes and make them more sensitive to insulin. In addition, metformin modestly decreases blood triglyceride and total cholesterol levels.
Pharmacokinetics
- Bioavailability: 50-60%
- Protein bound: Minimal
- Metabolism: Not by liver
- Half-Life: 4-9 hr
- Excretion: Urine (90%, by tubular secretion)
Administration
- Administer with a meal.
- Make sure patient swallows extended-release tablets whole without crushing or chewing.
- Don’t administer extended-release tablets to children.
- Know that drug is given with diet therapy, sulfonylureas, or both.
Contraindications
- Hypersensitivity to drug
- Acute or chronic metabolic acidosis (including diabetic ketoacidosis) with or without coma
- Underlying renal dysfunction
- Heart failure requiring drug therapy
Precautions:
- Renal impairment, myocardial infarction, cerebrovascular accident, hypoxia, sepsis, pituitary deficiency or hyperthyroidism, dehydration, hypoxemia, chronic alcohol use
- Elderly or debilitated patients
- Pregnant or breastfeeding patients
- Children (safety not established).
Adverse reactions
- GI: diarrhea, nausea, vomiting, abdominal bloating
- Metabolic: lactic acidosis
- Other: unpleasant metallic taste, decreased vitamin B12 level
Patient monitoring
- When switching from chlorpropamide, stay alert for hypoglycemia during first 2 weeks of metformin therapy; chlorpropamide may stay in body for prolonged time. Conversion from other standard oral hypoglycemics requires no transition period.
- Monitor blood glucose level closely. If it isn’t controlled after 4 weeks at maximum dosage, oral sulfonylurea may be added.
- Monitor kidney and liver function tests, particularly in elderly patients.
- Assess hematologic parameters and vitamin B12 levels at start of therapy and periodically thereafter.
- Watch for signs and symptoms of lactic acidosis. Stop drug if acidosis occurs. To aid differential diagnosis, check electrolyte, ketone, glucose, blood pH, lactate, and metformin blood levels.
- Periodically monitor glucose and glycosylated hemoglobin levels to evaluate drug efficacy
Patient teaching
- Teach patient about diabetes and importance of proper diet, exercise, weight control, and blood glucose monitoring.
- Inform patient that drug may cause diarrhea, nausea, and upset stomach. Advise him to take it with meals to reduce these effects, and tell him that adverse effects often subside over time.
- Teach patient to recognize and immediately report signs and symptoms of acidosis, such as weakness, fatigue, muscle pain, dyspnea, abdominal pain, dizziness, light-headedness, and slow or irregular heartbeat.
- Advise patient to report changes in health status (such as infection, persistent vomiting and diarrhea, or need for surgery). These may warrant dosage decrease or drug withdrawal.
- As appropriate, review all other significant and life-threatening adverse reactions and interactions, especially those related to the drugs, tests, herbs, and behaviors mentioned above.
Nursing Considerations
- Give metformin tablets with food, which decreases and slightly delays absorption, thus reducing risk of adverse GI reactions. Give E.R. tablets with evening meal; don’t break or crush them.
- Expect prescriber to alter dosage if patient has a condition that decreases or delays gastric emptying, such as diarrhea, gastroparesis, GI obstruction, ileus, or vomiting.
- Expect to assess BUN and serum creatinine level before and during long-term therapy in those at increased risk for lactic acidosis.
- Monitor patient’s hepatic function, as ordered, because impaired hepatic function may significantly reduce the liver’s ability to clear lactate, predisposing the patient to lactic acidosis.
- Monitor patient’s blood glucose level to evaluate drug effectiveness. Assess for hyperglycemia and the need for insulin during times of increased stress, such as infection and surgery.
- Withhold drug, as ordered, if patient becomes dehydrated or develops hypoxemia or sepsis because these conditions increase the risk of lactic acidosis.
- Iodinated contrast media used in radiographic studies increases risk of renal failure and lactic acidosis during metformin therapy. Expect to withhold drug for 48 hours before and after testing
2.Pioglitazone
| Pioglitazone |
| Availability Tablets: 15 mg, 30 mg, 45 mg |
| Indications and dosages ➣ Adjunct to diet and exercise to improve glycemic control in type 2 (non-insulin-dependent) diabetes mellitus Adults: 15 to 30 mg/day; may increase to 45 mg/day if needed |
Mechanism of Action
Decreases insulin resistance by enhancing the sensitivity of insulin-dependent tissues, such as adipose tissue, skeletal muscle, and the liver, and reduces glucose output from the liver. Drug activates peroxisome proliferator-activated receptor-gamma (PPARg) receptors, which modulate transcription of insulin-responsive genes involved in glucose control and lipid metabolism. In this way, pioglitazone reduces hyperglycemia, hyperinsulinemia, and hypertriglyceridemia in patients with type 2 diabetes mellitus and insulin resistance. However, to work effectively, pioglitazone needs endogenous insulin. Unlike sulfonylureas, it doesn’t increase pancreatic insulin secretion.
Pharmacokinetics
- Peak plasma time: 2-4 hr (delayed by food)
- Protein bound: >99%
- Metabolized by hepatic CYP2C8 and CYP3A4 into active metabolites
- Half-life: 3-7 hr
- Excretion: Urine (15-30%)
Administration
- Give with or without food.
- Know that drug may be used with sulfonylureas, metformin, or insulin when combination of diet, exercise, and monotherapy doesn’t achieve adequate glycemic control.
Contraindications
- Hypersensitivity to drug, its components, or rosiglitazone
- Established New York Heart Association Class III or IV heart failure
Precautions:
- Edema, hepatic impairment
- Symptomatic heart failure (use not recommended)
- Female patients of childbearing age
- Pregnant or breastfeeding patients
- Children (safety and efficacy not established).
Adverse reactions
- CNS: headache
- CV: congestive heart failure (CHF) or exacerbation of CHF
- EENT: sinusitis, pharyngitis
- Hematologic: anemia Metabolic: aggravation of diabetes mellitus, hypoglycemia, hyperglycemia
- Musculoskeletal: myalgia
- Respiratory: upper respiratory infection
- Other: tooth disorders, pain, edema
Patient monitoring
- Monitor patient carefully for signs and symptoms of heart failure (including excessive, rapid weight gain; dyspnea; and edema) after initiation and after dosage increases. Consider discontinuation or dosage reduction if these symptoms appear.
- Assess patient’s weight and compliance with diet and exercise program.
- Monitor liver function tests before and during therapy.
- Monitor glycosylated hemoglobin, hemoglobin, hematocrit, and blood glucose levels.
- Assess for signs and symptoms of hypoglycemia or hyperglycemia.
Patient teaching
- Instruct patient to take exactly as prescribed. Tell him he may take drug without regard to food.
- Tell patient drug may increase his risk for EENT and respiratory infections. Instruct him to contact prescriber if symptoms occur.
- Advise patient to immediately report unexplained nausea, vomiting, abdominal pain, fatigue, anorexia, dark urine, fever, trauma, infection, rapid weight gain, edema, or shortness of breath.
- Tell premenopausal anovulatory patient that drug may cause ovulation. Recommend use of reliable contraception.
- Advise female of childbearing age to contact prescriber promptly if pregnancy occurs.
- As appropriate, review all other significant and life-threatening adverse reactions and interactions, especially those related to the drugs, tests, and herbs mentioned above.
Nursing Considerations
- Be aware that pioglitazone isn’t recommended for patients with symptopmatic heart failure.
- Be prepared to monitor liver function test results before therapy begins, every 2 months during first year, and annually thereafter, as ordered, because drug is extensively metabolized in the liver. Expect to stop drug if jaundice develops or ALT values exceed 2.5 times normal.
- Assess for signs and symptoms of hypoglycemia, especially if patient is also taking another antidiabetic drug.
- Monitor fasting glucose level, as ordered, to evaluate effectiveness of therapy.
- Monitor glycosylated hemoglobin level to assess drug’s long-term effectiveness.
REFERENCES
- Robert Kizior, Keith Hodgson, Saunders Nursing Drug handbook,1st edition 2024, Elsevier Publications. ISBN-9780443116070
- McGraw Hill- Drug Handbook, Seventh Edition, 2013, McGraw Hill Education Publications,9780071799430.
- April Hazard, Cynthia Sanoski, Davi’s Drug Guide for Nurses -Sixteenth Edition 2019, FA Davis Company Publications,9780803669451.
- Jones and Bartlet, Pharmacology for Nurses, Second Edition, 2020, Jones and Bartlet Learning Publications, ISBN 9781284141986.
- Nursebro.com, Search – Nursebro
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