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Metformin: what is it, how does it work and how does the drug work for diabetes and not only
Index of contents
- For the treatment of which diseases is metformin used
- How does metformin work
- How is metformin taken
- What can be the side effects
- What are the contraindications
Metformin was approved by the FDA in 1994. It is an antidiabetic drug that is precisely used in the treatment of type 2 diabetes mellitus. Metformin is available in both immediate and prolonged release. It is also available in several products combined with other antidiabetic agents.
In our article we will look at what diseases it is used for, how it acts, how it is taken and what side effects can be.
If you have been diagnosed with diabetes 2 and would like to receive more information about metformin therapy, the benefits and possible side effects, you can seek advice from an online diabetologist to ask as many questions as you want.
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For the treatment of which diseases is metformin used
Typically when first diagnosed with type 2 diabetes, the first line of treatment involves diet, exercise, and lifestyle change. If these measures are not effective in reducing hyperglycemia, the prescription of metformin is often used as monotherapy or in combination.
According to the American Diabetes Association (ADA), metformin is the preferred first-line pharmacological agent in patients with type 2 diabetes mellitus in both adults and children aged ten years and older. It is not indicated in type 1 diabetes mellitus. According to Standards of Medical Care in Diabetes 2018, if a patient's glycated hemoglobin is less than 9% at the time of diagnosis, it is recommended to start monotherapy with metformin.
If, on the other hand, glycated hemoglobin is greater than 9%, metformin is recommended for use in combination therapy.
Metformin also has several indications not approved by the FDA, including gestational diabetes, management of antipsychotic-induced weight gain, prevention of type 2 diabetes, and both treatment and prevention of polycystic ovary syndrome (PCOS). Currently, metformin is the only antidiabetic recommended by the ADA for pre-diabetes. As for potential indications, researchers are studying metformin for its possible anti-aging, anticancer and neuroprotective effects.
How does metformin work
Metformin is a biguanide drug. It reduces blood glucose levels by decreasing glucose production in the liver, decreasing intestinal absorption and increasing insulin sensitivity. Metformin reduces both basal and postprandial blood sugar.
In Polycystic ovary Syndrome, metformin lowers insulin levels thus inducing reduction in luteinizing hormone and androgen levels. It allows thanks to this mechanism to normalize the menstrual cycle. It is important to warn fertile women that while taking metfomine there is a potential increase in the chances of becoming pregnant.
In gestational diabetes, metformin is recommended as an alternative to insulin. Hyperglycemia, as is well known, is associated with congenital malformations.
Metformin is also administered for the purpose of reducing body weight. In fact, it has been seen that it has the ability to induce modest weight loss. It has also been shown to have cardioprotective effects.
Metformin begins to act about 3 hours after its intake. It has a half-life of 20 hours. It is not metabolized in the liver, nor does it have a substantial protein binding.
It is then eliminated by the kidney, mostly unchanged, also for this reason it is very important to monitor kidney function.
How is metformin taken
Metformin is an oral medication typically dosed from 500 to 2550 mg per day. It is administered on a full stomach to reduce the occurrence of possible gastrointestinal disorders. The daily dose is often titrated weekly in 500 mg or 850 mg increments to reduce this risk. The recommendations are to take metformin at the same time every day.
Prolonged-release tablets are usually taken once a day with an evening meal and should be swallowed with a full glass of water.
What can be the side effects
Metformin is generally considered safe and well tolerated. Gastrointestinal side effects, including diarrhea, nausea and vomiting, are very common and typically occur in up to 30% of patients taking metformin.
Less frequently, it has been seen that some patients may experience chest discomfort, headache, sweating, hypoglycemia, weakness and rhinitis. Recall that very often patients who have been taking metformin for a long time may develop reduced levels of vitamin B12. It is therefore very important to monitor this condition especially in patients with anemic or peripheral neuropathy. Vitamin B12 supplementation may be required.
Metformin may cause lactic acidosis. This side effect is rare but severe and has an incidence rate of 1 in 30,000 patients. Lactate accumulates in the body and cannot be eliminated easily, which leads to metabolic acidosis.
This lowering of blood pH can cause nonspecific signs and symptoms, including malaise, respiratory distress, elevated lactate levels, and anion gap acidosis. Patients with hepatic or renal insufficiency, the elderly, patients who have recently undergone surgery, those suffering from hypoxia or alcoholism are at risk of developing this condition.
All these risk conditions tend to decrease the pH in the blood. It is very important not to consume alcohol excessively while taking metformin. Although this side effect is rare, lactic acidosis can cause hypotension, hypothermia, and death.
Specific drug interactions may increase the risk of developing lactic acidosis. These include but are not limited to bupropion,carbonic anhydrase inhibitors, cephaleina.
Other drug interactions may contribute to an increase in the hypoglycemic effect. Some of these drugs include androgens, alpha-lipoic acid, salicylates, selective serotonin reuptake inhibitors, quinolones, protionamide, pegvisomant and other antidiabetic agents.
What are the contraindications
Metformin is contraindicated in patients with severe renal dysfunction, defined as a glomerular filtration rate (GFR) of less than 30 ml/min/1.732. This limitation also equals serum creatinine (SCr) greater than or equal to 1.5 in men and 1.4 in women or abnormal creatinine clearance (CrCl). Any potentially toxic drugs for the kidneys should not be used simultaneously.
The metformin package insert recommends discontinuation of metformin before administering iodinated contrast media to patients with GFR below 60 ml/min/1,732, risk factors for lactic acidosis or intra-articular contrast administration. Metformin can be restarted after the procedure once the patient's GFR has normalized. Due to the risk of lactic acidosis, the package insert recommends discontinuing metformin if nausea, vomiting and dehydration occur.
Recommendations also include avoiding metformin in patients with liver failure or unstable heart failure. In addition, administration of metformin should be discontinued before undergoing any surgery.
Other contraindications include hypersensitivity to metformin and metabolic acidosis.
Toxicity
Overdose of cheap metformin is related to hypoglycemia and lactic acidosis. If your doctor suspects lactic acidosis due to toxic levels of metformin, you should stop the drug immediately and begin hemodialysis. Metformin is an easily dialysable drug due to its small molecular weight and lack of protein binding. Supportive therapy is used in the treatment of metformin toxicity, since no antidote is used.
Monitoring
Monitoring for any oral antidiabetic agent includes fasting blood glucose, postprandial blood glucose, and glycated hemoglobin A1C (HbA1c) every 3-6 months. For Facts and Comparisons, physicians should monitor kidney function via GFR before starting therapy and then periodically.
Patients with a GFR of 60 to 45 ml/min/1.732 should be monitored every 3 to 6 months. Patients with a GFR of less than 45 ml/min/1.732 should instead be monitored every three months. The ADA also recommends that vitamin B12 levels be monitored frequently, particularly in patients with anaemia or peripheral neuropathy. Patients taking concomitant medications, which may cause an increased risk of lactic acidosis, should be monitored frequently.
