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Metformin is an antihyperglycemic drug that improves glucose tolerance and reduces basal and postprandial blood sugars in patients with type 2 diabetes. Insulin secretion remains unchanged with metformin treatment, whereas fasting insulin levels and plasma insulin responses throughout the day may be reduced [1-5].
Metformin is a clinically widely used hypoglycemic drug, so what are its contraindications and precautions? Let’s take a look at the finishing of Jie Xiaoyao!
Contraindications
Metformin is contraindicated in patients who:
1. Severe renal insufficiency [estimated glomerular filtration rate (eGFR) less than 30mL/min/1.73m2];
2. Allergic to metformin;
3. Acute or chronic metabolic acidosis, including diabetic ketoacidosis (with or without coma) [1-3].
Notes
1
Lactic acidosis
There have been postmarketing cases of metformin-related lactic acidosis, including fatal cases. These cases are mild with nonspecific symptoms of malaise, myalgia, abdominal pain, respiratory distress, or lethargy; however, hypotension and intractable bradyarrhythmias can occur with severe acidosis.
Metformin-related lactic acidosis is characterized by elevated blood lactate concentrations (>5 mmol/L), anion gap acidosis (without evidence of ketonuria or ketosis), and lactate:acetone The proportion of acid is increased; metformin plasma levels are usually >5 μg/mL. Metformin reduces the level of lactate uptake by the liver and increases lactate levels in the blood, which may lead to an increased risk of lactic acidosis, especially in patients who are already at such risk.
If metformin-related lactic acidosis is suspected, immediate medical attention should be given to general supportive measures, and metformin should be discontinued immediately. If lactic acidosis is diagnosed or strongly suspected in metformin-treated patients, prompt hemodialysis is recommended to correct acidosis and remove accumulated metformin (under favorable hemodynamic conditions, metformin hydrochloride is dialyzable with clearance up to 170 mL). /min). Hemodialysis often results in reversal and recovery of symptoms.
For each known and possible risk factor for metformin-related lactic acidosis, recommendations for reducing and managing the risk of metformin-related lactic acidosis are provided below:
Before starting metformin, test for eGFR. Metformin is contraindicated in patients with eGFR <30 mL/min/1.73 m2.
Initiation of metformin is not recommended in patients with an eGFR between 30-45 mL/min/1.73 m2.
All patients taking metformin have their eGFR tested at least annually. Renal function should be assessed more frequently in patients at risk for renal impairment (eg, the elderly).
In patients taking metformin with an eGFR less than 45 mL/min/1.73 m2, the benefits and risks of continued metformin therapy should be assessed.
Renal Impairment – Postmarketing studies have shown that metformin-related lactic acidosis cases occurred primarily in patients with severe renal impairment. Because metformin is primarily excreted by the kidneys, the risk of metformin accumulation and metformin-related lactic acidosis increases with the severity of renal impairment. Clinical recommendations for metformin use in patients based on renal function include:
Before starting metformin, test for eGFR. Metformin is contraindicated in patients with eGFR <30mL/min/1.73m2.
Metformin is not recommended for patients with eGFR between 30-45mL/min/1.73m2.
All patients taking metformin have their eGFR tested at least annually. Renal function should be assessed more frequently in patients at risk for renal impairment (eg, the elderly).
For patients taking metformin with an eGFR less than 45mL/min/1.73m2, the benefits and risks of continued metformin therapy should be assessed.
Drug interactions
Metformin may increase the risk of metformin-related lactic acidosis when co-administered with certain drugs: drugs that impair renal function, cause significant hemodynamic changes, interfere with acid-base balance, or increase metformin accumulation. If these conditions occur, the patient should be monitored more frequently.
Age 65 and over
The risk of metformin-related lactic acidosis increases with age, because older patients are more likely to develop liver, kidney, or heart damage than younger patients. Renal function should be assessed more frequently in elderly patients.
Radiological studies of contrast agents
The use of intravascular iodinated contrast media in metformin-treated patients resulted in a dramatic decrease in renal function and lactic acidosis. For patients with eGFR between 30-60mL/min/1.73m2, liver impairment, history of heart failure, or alcoholism, or patients about to be given intra-arterial iodinated contrast, at or before surgery with iodinated contrast imaging , metformin should be discontinued. eGFR was reassessed 48 h after the imaging procedure and metformin was restarted if renal function was stable.
Surgery or other procedures
Abstaining from food and fluids during surgery or other procedures may increase the risk of hypovolemia, low blood pressure, and kidney damage. Metformin should be temporarily discontinued when the patient restricts food and fluid intake.
Hypoxic state
Some postmarketing cases of metformin-related lactic acidosis have been reported in the setting of acute congestive heart failure (particularly with hypoperfusion and hypoxemia) case. Cardiovascular failure (shock), acute myocardial infarction, sepsis, and other conditions associated with hypoxemia are all associated with lactic acidosis and may lead to prerenal azotemia. Therefore, metformin should be discontinued when such an event occurs.
Excessive drinking
Alcohol increases the effect of metformin on lactate metabolism. Patients should be warned against excessive alcohol consumption during metformin treatment.
Impaired liver function
Metformin-related lactic acidosis occurs in patients with impaired hepatic function. This may be due to impaired lactate clearance, resulting in elevated blood lactate levels. Therefore, avoid metformin in patients with clinical or laboratory evidence of liver disease.
2
Vitamin B12 deficiency
In a 29-week clinical trial of metformin hydrochloride tablets, previously normal serum vitamin B12 levels decreased to below normal levels in approximately 7% of patients. This may be due to interference with the absorption of vitamin B12 by the vitamin B12-intrinsic factor complex and may also be associated with anemia, but this phenomenon appears to be rapidly reversed after discontinuation of metformin or vitamin B12 supplementation.
Certain groups of people (people with insufficient intake or absorption of vitamin B12 or calcium) seem to be prone to lower-than-normal levels of vitamin B12. For patients on metformin, hematological parameters should be measured annually, and vitamin B12 levels should be measured at 2-3 year intervals, and any abnormalities that arise should be managed.
3
Can cause hypoglycemia in combination with insulin, etc.
Insulin and insulin secretagogues such as sulfonylureas are known to cause hypoglycemia. There may be an increased risk of hypoglycemia when metformin is used in combination with insulin/insulin secretagogues. Therefore, lower doses of insulin or insulin secretagogues may be required to minimize the risk of hypoglycemia when used in combination with metformin.
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