Metformin Nursing Considerations

Metformin Nursing Implications

Metformin Nursing Pharmacology

Metformin is a biguanide agent developed from galegine, aguanidine derivative found in Galega officinalis or goat’s rue.

It is used in conjunction with diet and exercise used as a monotherapy or in combination with other antidiabetic agents.

It comes in both immediate-release and extended-release forms with FDA-approved and non-FDA-approved indications.

The American Diabetes Association (ADA) recommended metformin as the first-line agent in children ten years of age and adults with type 2 diabetes mellitus.

It is the only ADA-recommended antidiabetic agent for pre-diabetes and is not indicated for patients with type 1 diabetes mellitus.

It is believed that metformin is the world’s most widely prescribed antidiabetic medication. Currently, metformin is being studied for its possible weight reduction effect in patients with fragile X syndrome, anticancer, anti-aging, and neuroprotective effects.

Indications for Metformin

Metformin is an FDA-approved agent used to treat type II diabetes mellitus and gestational diabetes. It lowers blood sugar levels by improving the body’s sensitivity to insulin. It is prescribed when diet and exercise alone have not been effective in controlling blood sugar levels.

Although hypoglycemia commonly occurs during intense exercise, calorie deficit, or when used with other blood glucose-lowering agents. Some evidence shows that it reduces body weight in obese patients in the absence of diabetes.

The use of metformin during pregnancy compared to insulin alone is safe for both the mother and the baby, but unclear for long-term safety. Women taking metformin for gestational diabetes gain less weight and are less likely to develop pre-eclampsia during pregnancy.

On the other hand, the babies born have less visceral fat and lower birth weight, making them less likely to develop insulin resistance in later life. Metformin has several non-FDA-approved indications, including polycystic ovarian syndrome (PCOS), antipsychotic-induced weight gain, and prevention of type 2 diabetes.

Metformin treats PCOS by lowering blood sugar levels and insulin and improving ovulation by having a regular monthly menstrual cycle. In patients with prediabetes, there is moderate-quality evidence that it reduces the risk of developing type 2 diabetes when compared to diet and exercise or a placebo.

Metformin is not indicated for patients with type 1 diabetes mellitus due to the lack of efficacy from being insulin dependent thereby causing uncontrolled blood glucose levels. Metformin may decrease the risk for diabetic-related complications such as nerve damage, eye problems (changes or loss of vision), kidney failure, gum disease, stroke, and heart attack.

It also prevents some vascular complications and modestly reduces triglyceride levels and low-density lipoprotein levels.

Actions of Metformin

Metformin’s mechanism of action is unique from other oral antihyperglycemic drugs because:

Metformin increases the sensitivity of insulin by increasing peripheral uptake and utilization leading to decrease blood glucose levels, type 2 diabetes management, and exerting positive effects on glycemic control.
After ingestion, the uptake of metformin into the liver cells or hepatocytes activates AMP-activated protein kinase (AMPK), an enzyme that regulates glucose metabolism. It decreases blood glucose levels by decreasing gluconeogenesis or hepatic glucose production, thereby inhibiting fat synthesis and fat oxidation, reducing hepatic lipid stores and liver sensitivity to insulin.
In the intestines, it increases anaerobic glucose metabolism in the intestinal cells, leading to reduced glucose uptake and increased delivery of lactate to the liver. It promotes the metabolism of glucose by increasing glucagon-like peptide I and increasing gut utilization of glucose.
Metformin has an anorexiant effect in most people causing a decrease in caloric intake. It is used to decrease antipsychotic-induced weight gain by suppressing appetite and decreasing insulin resistance.

Pharmacokinetics of Metformin

Metabolism. Metformin is a hydrophilic base that exists at physiological pH as cationic species. Its disposition is unaffected by diabetes and slightly affected by the use of different formulations. It is not metabolized but is widely distributed into the body tissues by organic cation transporters and is excreted unchanged in the urine by active tubular secretion in the kidneys.

Absorption. The immediate-release form is rapidly absorbed in the small intestine with about 20% of the total dose absorbed in the duodenum, 60% in the jejunum to the ileum, and small amounts in the rest of the colon. The rest is excreted in the feces and urine.

Half-life. The extended-release formulation has a similar onset of effect with a half-life of 6.5 hours and a 24-hour duration of action. Although the half-life may be prolonged in patients with renal impairment and can result in fatal lactic acidosis from the suppression of gluconeogenesis and inhibition of lactic acid metabolism in the liver.

Elimination. The average elimination half-life in plasma is 6.2 hours and is undetectable in blood plasma after 24 hours of a single oral dose. Metformin is absorbed slowly under fasting conditions with an oral bioavailability of 50-60%. Its peak plasma concentration is reached within 1-3 hours for immediate-release metformin and 4-8 hours for extended-release formulations. Its low lipid solubility requires a transporter to enter the cells with rapid passive diffusion through cell membranes. Giving metformin with food may decrease the extent and delay absorption. Liver concentrations of metformin are 2 to 3 times higher than plasma concentrations due to portal vein absorption and first-pass uptake by the liver. Therefore, the liver is presumed as the primary site of metformin function due to the inhibition of hepatic glucose output and increased serum concentration of metformin in the hepatocytes.

Active tubular secretion in the kidney is the main route of metformin elimination. Drug concentration generally reaches the circulation via the portal vein, passes the liver, and is rapidly cleared by the kidneys. High clearance of metformin is affected by the presence of transporters in the kidney, the low molecular weight associated with negligible plasma protein binding, and the low lipid solubility for passive reabsorption. Metformin is a highly ionized, water-soluble drug being absorbed, distributed, and eliminated by transporters. A change in pharmacokinetics can predispose patients to either over or under-dosing which will eventually result in adverse reactions or therapeutic failure.

Side Effects of Metformin

Many patients taking metformin do not have serious side effects and some may go away as the body adjusts to the medication. The most common side effects include:

Nausea and vomiting
Abdominal or stomach discomfort
Abdominal distention or bloating
Diarrhea
Heartburn
Flatulence
Metallic taste in the mouth
Decrease or loss of appetite
Vitamin B12 deficiency
Fever or chills
A general feeling of discomfort
Physical weakness or asthenia
Muscle pain (myalgia) or cramping
Fast or shallow breathing
Hoarseness or cough
Lower back or side pain
Painful or difficult urination
Sleepiness

Metformin does not usually cause hypoglycemia but may occur if it is prescribed with other diabetic agents. Symptoms include dizziness, sweating, palpitations, tingling sensations, and blurring of vision. Serious allergic reactions to metformin are rare, however, report difficulty of breathing, rashes, itching, swelling, or severe dizziness immediately.

Adverse Reactions of Metformin

Despite the potential benefits, caution in using the drugs for individuals with certain comorbidities due to the perceived risk of serious adverse reactions such as:

Gastrointestinal upset. High doses and long-term use of metformin are associated with malabsorption of vitamin B12, calcium intake or absorption, and increased homocysteine levels. This can be avoided by beginning at low doses and increasing the dose gradually.
Lactic acidosis. Metformin-associated risk factors for lactic acidosis include the old age population (65 or older), renal impairment, hepatic impairment, hypoxic state, surgery, procedures with contrast, concomitant use of certain drugs, and excessive alcohol intake. Metformin decreases the liver’s uptake of lactate, thereby increasing lactate levels in the blood and leading to metabolic acidosis. Lactate production may also take place in the large intestine potentially contributing to metformin-associated lactic acidosis for those with risk factors. Lactate builds up in the body cannot be eliminated easily lowering the blood pH causing nonspecific signs and symptoms such as respiratory distress, hypotension, hypothermia, severe vomiting and/or diarrhea, myalgia, malaise, resistant bradyarrhythmia, and increased somnolence.
Overdose. The blood or plasma metformin concentrations at 1-4mg/L are the therapeutic levels of metformin and acute overdose at 80-200 mg/L is usually fatal. Symptoms of overdose include diarrhea, abdominal pain, vomiting, tachycardia, drowsiness, and hypoglycemia or hyperglycemia. There is no specific antidote known for metformin overdose and treatment is generally supportive.

Drug Interactions with Metformin

Nurses should monitor patients who are concomitantly taking the following medications with metformin. Specific drug interactions that may increase the risk for lactic acidosis include:

Cephalexin
Cimetidine
Ethanol
Bupropion
Topiramate
Glaucoma drugs
Carbonic anhydrase inhibitors
Iodinated contrast agents
Dolutegravir
Ranolazine
Glycopyrrolate
Lamotrigine

Other drug interaction that may increase the hypoglycemic effect of metformin includes:

Salicylates
Quinolones
Selective serotonin reuptake inhibitors
Alpha-lipoic acid
Androgens
Phenothiazine
Pegvisomant
Prothionamide
Other antidiabetic agents

Taking the following medications with metformin makes it less effective in lowering blood sugar. These includes:

diuretics
nicotinic acid
phenytoin
corticosteroids
estrogens
isoniazid
thyroid drugs

Some increase the amount of metformin in the body increasing side effects such as calcium channel blockers.

Nursing Considerations When Using Metformin

Administer metformin daily with a meal at the same time every day with a full glass of water to prevent stomach upset. It is usually titrated weekly in increments of 500mg or 850mg to reduce GI upset. Titration to maximum doses is not recommended in malnourished, debilitated, and old-age patients.
Instruct the patient to avoid chewing, crushing, or breaking an extended-release tablet and swallow it whole. In case of a missed dose, take it as soon as possible and go back to the regular dosing schedule. Do not double dose and abruptly stop this medication.
Monitor blood sugar levels regularly and keep track of the results to determine if the dosage may need to be increased or decreased.
Encourage increased fluid intake and withhold the medication if patients experience dehydration, prolonged diarrhea, prolonged vomiting, and/or prerenal azotemia.
Instruct the patient to limit alcohol intake while using this medication to decrease the risk of developing hypoglycemia and lactic acidosis.
Instruct the patient to inform the primary care provider before any type of imaging studies requiring a dye injected into the veins and for any surgery to temporarily stop taking metformin that might cause oliguria. The usual dose may be resumed 48 hours after the procedure if the kidney function is tested and found to be normal.
Encourage patients with diabetes mellitus to eat nutritious foods, have regular exercise, and avoid smoking for the medication to work and improve the patient’s condition. Instruct to take vitamin B12 supplements to prevent deficiency.
Caution should be given in patients with severe renal dysfunction (defined as glomerular filtration rate GFR less than 30ml/min/1.732, abnormal creatinine clearance, and serum creatinine greater than or equal to 1.5 in men and 1.4 in women). Any potential renal toxic medication should not be used concomitantly.
Educate the patient that blood glucose improvement may take about 1 to 2 weeks and the full blood glucose control effect may take up to 2 to 3 months. Give information about signs and symptoms of hypoglycemia and hyperglycemia and interventions to be done in case of such an event.
Educate premenopausal women and those with insulin resistance associated with polycystic ovary syndrome (PCOS) about the increased chance of pregnancy and discuss birth control options with the primary care provider.
Educate the patient about the importance of fasting blood glucose, postprandial blood glucose, hemoglobin A1C (HbA1c), and renal function monitoring every 3 to 6 months. Frequent checking of vitamin B12 levels for patients in long-term metformin use with anemia or peripheral neuropathy.
Educate the patient about the signs and symptoms of an overdose and lactic acidosis due to toxic metformin levels and immediately discontinue the medication. Explain supportive care and possible hemodialysis, as there is no antidote for metformin toxicity.

Nursing Care Plan for Patients on Metformin

Possible Metformin Nursing Diagnoses

Risk for Unstable Blood Glucose Levels
Risk for Impaired Kidney Function
Nausea and Vomiting
Diarrhea

Nursing Assessment

Metformin Nursing Interventions	Rationale
Assess the patient’s blood glucose level through a finger prick test or use a sensor if the patient has one. Also, collect a blood sample for HbA1C as instructed by the physician.	To establish a baseline blood glucose level upon admission, and to confirm the indication for administering metformin.
Check the patient’s allergy status.	Alternatives to metformin should be considered in case of allergy.
Assess the patient’s ability to self-administer the medication.	To assess and boost the patient’s confidence in self-administration and to check for any potential problems with administration.
Check the patient’s renal function.	Caution is highly warranted with patients who have severe renal dysfunction as taking metformin may make it worse.
Assess if the female patient has insulin resistance related to PCOS.	Recent studies show that metformin can increase the chance of pregnancy in women with insulin resistance related to PCOS.

Nursing Planning and Intervention

Metformin Nursing Interventions	Rationale
Administer metformin at the same time each day.	To ensure medicine compliance and lower the risk of high blood glucose levels.
Advise the patient that metformin should be taken with food and a full glass of water.	Metformin may irritate the lining of the stomach (non-symptomatic gastritis), so it should be taken with meals.
Advise the patient to prevent drinking excessive amounts of alcohol while on metformin.	Metformin combined with excessive amounts of alcohol may cause lactic acidosis and dullness of the patient’s senses.
Educate the patient about the action, indication, common side effects, and adverse reactions to note when taking metformin. Instruct the patient on how to self-administer metformin.	To inform the patient on the basics of metformin, as well as to empower him/her to safely self-administer the medication.
Advise the patient to report any feeling of nausea or episode of vomiting.	Nausea and vomiting are common side effects of metformin, especially during the initial doses. Uncontrolled nausea and vomiting can be symptoms of metformin overdose.
Routinely check for the renal function of the patient.	Metformin can contribute to kidney failure if given to patients with severe renal dysfunction.

Nursing Evaluation

Metformin Nursing Interventions	Rationale
Ask the patient to repeat the information about metformin, such as the right dose and the maximum dose per day.	To evaluate the effectiveness of health teaching on metformin.
Monitor the patient’s renal function through routine blood tests.	To ensure that the metformin did not cause any renal dysfunction.
Monitor the patient’s response to metformin by checking blood glucose levels at least 4 times a day.	To check if metformin is effective or if another type of pain relief is needed.
Monitor for any symptoms of nausea and vomiting, GI upset, or diarrhea, and treat them as they appear. Review the need to change to another antidiabetic drug with the physician if the patient is not tolerating it.	Metformin may cause diarrhea or other signs of GI upset.

Nursing References

Ackley, B. J., Ladwig, G. B., Makic, M. B., Martinez-Kratz, M. R., & Zanotti, M. (2020). Nursing diagnoses handbook: An evidence-based guide to planning care. St. Louis, MO: Elsevier. Buy on Amazon

Gulanick, M., & Myers, J. L. (2022). Nursing care plans: Diagnoses, interventions, & outcomes. St. Louis, MO: Elsevier. Buy on Amazon

Ignatavicius, D. D., Workman, M. L., Rebar, C. R., & Heimgartner, N. M. (2020). Medical-surgical nursing: Concepts for interprofessional collaborative care. St. Louis, MO: Elsevier. Buy on Amazon

Silvestri, L. A. (2020). Saunders comprehensive review for the NCLEX-RN examination. St. Louis, MO: Elsevier. Buy on Amazon

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