Type 2 diabetes accounts for more than 95% of the diabetes cases in America, that afflicts around 34 million people. While diabetes was earlier known to onset after the age of 45, it is now increasingly affecting younger age groups. Among the different types of medication used worldwide to treat the condition, metformin is considered as the first choice of medication. The antihyperglycemic has a record of being prescribed to more than 122 million individuals globally. While it is by far the most popular drug of choice, it is not free from adverse effects. Here is a detailed look at the side effects of metformin to help patients manage and mitigate conditions effectively.
Drug overview and side effects of metformin
Before we look at the side effects of metformin it is important to understand more about the drug through a quick overview. By virtue of its ability to lower blood glucose levels without causing hypoglycemia, it is classified as an antihyperglycemic. Available in regular and extended-release dosages, it is an insulin sensitizer, which means that it brings about a reduction in the insulin resistance. It also reduces the plasma fasting insulin levels considerably, in addition to helping patients benefit from weight loss. As a result of this combination of positive effects, it has become the most popular choice for type 2 diabetes patients who are obese.
Mechanism of action of metformin
Side effects of medications are attributed mainly to the mechanism of action, as this typically results in undesirable effects. It is therefore necessary to understand the mechanism of action to learn all about the side effects of metformin. Metformin has a mechanism of action distinct from other medications that are used as oral formulations to treat type 2 diabetes. It works by reducing the production of hepatic glucose and by reducing the absorption of glucose in the intestines. Additionally, it works by improving insulin sensitivity. This is achieved by increasing the uptake of peripheral glucose, and the extent to which it is used.
Other remarkable actions include the inhibition of mitochondrial I activity, which is reportedly the main reason for the antidiabetic properties of the medication. The combination of all the actions brings about a reduction in blood glucose levels, helps in managing diabetes and brings about a significant impact on the need to control glycemic levels. After metformin has been ingested, it accumulates in in cells and mitochondria, as a result of the membrane potentials across plasma membrane. By preventing mitochondria I complex, the mechanism of action brings about regulation of glucose metabolism. Subsequently, gluconeogenesis is inhibited, apart from preventing fat synthesis, which in turn results in oxidation of fat. Other actions that result from this sequence includes an increase in liver sensitivity to insulin and a reduction in hepatic lipid stores.
Before we look at the side effects of metformin let’s round off about the mechanism of action of the antihyperglycemic. An increase in anaerobic glucose metabolism in the intestines results in a reduction of glucose uptake. Consequently, more lactate is delivered to the liver. Metformin is also known to promote the metabolism of glucose by increasing glucagon like peptide and the rate with which glucose is utilized.
Ideal dosages to prevent side effects of metformin
While side effects of metformin are attributed to the mechanism of action, it is also necessary to note that certain side effects are also attributed to the dosages. Individuals who take excessive dosages of the medication will also experience adverse effects. Here is a little guidance on the right dosage levels of the medication. Adults who take immediate release formulations for treating diabetes, are typically advised to take either 500 mg, 850 mg or 1000 mg. In the event that adults are recommended extended release formulations, the dosages are typically 500 mg, 750 mg and 1000 mg. Wherever adults are recommended oral solutions as formulations for treating diabetes, the dosage is 500 mg, 750 mg and 1000 mg.
Children who have been prescribed metformin for treating diabetes are typically recommended 500 mg, 850 mg and 1000 mg when the formulation is immediate release. In the case of children who take extended release formulations, the dosages are 500 mg, 750 mg and 1000 mg. Similarly, recommended dosages of oral solutions for treating diabetes in children is 500 mg, 750 mg and 1000 mg.
There are other considerations when it comes to dosages. For instance, an individual may be recommended metformin as part of treatment that includes other medication. Or metformin may be recommended for patients for the purpose of preventing type 2 diabetes. In such circumstances, the dosages will differ, with a cap on the maximum dosage that should be taken per day. This is not to exceed certain limits as per the combinations of medications.
How to handle overdose and toxicity
With the side effects of metformin covered, it is time to look at situations where an overdose could have resulted in toxicity. It is therefore necessary to learn how to handle and prevent such situations. One of the conditions associated with toxic overdose includes lactic acidosis, which has reportedly resulted in a few fatalities. Such conditions have typically begun with mild symptoms that included malaise, pain in the abdomen, or some form of respiratory issues. In a few cases other symptoms were associated with the onset, including hypotension. As a result of lactic acidosis, blood lactate levels are known to increase significantly. Certain conditions are known to increase the risk of lactic acidosis, including problems in the kidney, specific medications, advancing age, over indulgence in alcohol and impaired liver functions.
Commonly reported side effects of metformin
Some of the commonly reported side effects of metformin include an overall weakness that is medically known as asthenia. Patients are also likely to experience bouts of diarrhea, while some may experience gas that is not attributed to any other dietary or medical condition. Pain in the muscles is another possibility that could be experienced by patients, and this could accompany the general physical weakness. The upper respiratory tract could end up with an infection in individuals taking the medication as a result of the mechanism of action of metformin. Low levels of blood sugar are one of the possible outcomes of the medication.
Patients on the medication are likely to experience discomfort in the chest, and possible heartburn. Both of these conditions are linked to the side effects of metformin only when there are no known causes for the condition – such as a dietary issue. Patients have reported constipation, either accompanied or not accompanied by abdominal pain. The pain is also typically as a result of gastrointestinal issues arising out of the medication, and in rare cases is caused by lactic acidosis. Other manifestations commonly experienced include vomiting and nausea. There is a possibility of feeling cold and chill, that could also be accompanied by dizziness. As mentioned above, patients are likely to experience an impaired function of other medications or formulations, and this is best seen in the lower vitamin B-12 levels in the blood.
Side effects of metformin that are not common, or that are rare in nature
Here is a look at side effects that are not common or that are rare in nature. Some of these conditions may overlap with the commonly reported conditions above. In most individuals these conditions may be uncommon or rare, but for a few this could be common, depending on various other parameters. For instance, individuals are likely to experience some kind of anxiety, when on the medication. Similarly, blurred vision is a possibility in a few cases, while discomfort in the chest and breaking out into a cold sweat have also been reported by patients. Conditions such as difficulty in breathing, while being uncommon or rare, require urgent treatment. The heartbeat rate may turn irregular or start beating in a fast and racy manner. Feelings of warmth, a sudden tightening of the chest and slurred speech are other uncommon and rare side effects of metformin. Individuals may appear to be drunk as a result of certain conditions, while some find it extremely difficult to focus or concentrate.
Important conditions that need attention is hypoglycemia. While this is rare, this may occur when patients take the medication while continuing to be on insulin. This needs to be prevented and monitored to ensure that hypoglycemia does not onset in patients. Other conditions such as lactic acidosis also require medical attention due to a build-up of lactic acid. Finally, renal condition could worsen in patients with diabetes along with kidney ailments that are chronic in nature.
Drug interactions of metformin
The medication is also known to result in drug interactions apart from the listed side effects of metformin. The information provided herein is intended to be used as information and is not to replace the recommendations or advice of specialists. For instance, a treating specialist who prescribes metformin for treating diabetes will certainly be aware of the drug interactions. And the dosage is typically recommended after taking into consideration the possibilities of drug interaction. Therefore, it is wrong to change any medication or dosage on the basis of assumptions. However, in the event that the treating specialist is not informed of any other ongoing treatment or medication, it is likely to result in potential adverse effects. Hence, it is necessary to stay informed of possible interactions and inform the treating specialist of ongoing treatments and other medications or supplements in use.
Ethanol, loversol and contrast agents used for imaging are known to cause interactions and it is therefore necessary to understand and use the same accordingly. Metformin is known to have different reactions or drug interactions with various drugs on different scale. For instance, moderate interactions are reportedly observed in as many as 70+ drugs of various combinations. Similarly, the mild interactions of metformin with other drugs and drug combinations are reportedly witnessed in more than 80 different drugs.
Precautions to be taken in patients with certain conditions
It is necessary to take precautions in patients with certain conditions as this will help avoid side effects of metformin. For instance, patients with impaired renal functions will experience lesser renal clearance of the medication as the plasma and blood-life of the drug is likely to be extended. Similarly, the medication is not suitable for individuals suffering from certain known conditions – renal impairment, liver disease, and heart failure. Elderly patients are to be administered lower dosages. Patients who consume excessive amounts of alcohol or patients who drink habitually need to exercise caution while taking the medication. Individuals intending to undergo any kind of surgery are advised to stop the medication before the surgery, in other words medication is not to be taken during the pre-surgery preparatory period and for a short time immediately after the surgery, or as advised by specialists.
There is a possibility of increased mortality due to cardiovascular complications when on the medication. Women with PCOS (polycystic ovary syndrome) may experience mild complications as a result of the medication. Some of the side effects of metformin can be countered by changing the medication. For instance, when patients experience stress, or fever or any infection that is not attributed to other reasons, it is advised to stop the medication and replace it with insulin. This will help to mitigate or stop the side effects. Other possible outcomes of the medication include a lesser than normal effectiveness of other medications- vitamin B12, calcium, etc. As a result of reduced intake and absorption, of calcium and vitamin B12, the effectiveness is likely to reduce.
Instances where the medication is not considered as suitable
Apart from the side effects of metformin, there are specific instances when the medication is not considered as suitable for use. Metformin is not to be used for managing Type 1 diabetes, especially wherever it is insulin dependent. This is primarily because of the poor efficiency of the medication in treating the condition. Patients with certain pre-existing conditions are not to be administered the medication – this includes prenatal azotemia and dehydration. Similarly, patients who intend to undergo procedures such as iodinated contrast imaging are also to discontinue the medication temporarily. The medication is to be continued again, only when test results indicate that renal functionality is stable or has improved.
What happens when a patient abruptly stops taking the drug?
When patients abruptly stop taking the drug, there is a possibility of the condition worsening. It is therefore necessary to consult a specialist before taking a decision on stopping any medication for treating diabetes or any other condition that is serious in nature. Additionally, it may also be necessary to embrace changes in routine so as to lessen the effects of the condition. For instance, dietary modifications, adequate exercise and effective weight management programs or routines may be necessary as alternate options. Individuals who abruptly stop taking the medication without the condition being managed, are at risk of experiencing certain adverse effects. For instance, vision may end up being impaired with a condition commonly known as diabetic retinopathy. Patients may end up with renal impairment, or damage to the nerves in a condition that is medically known as diabetic neuropathy. Patients are also likely to experience sexual health complications, apart from issues in the feet, and heart complications.
Best methods to stop antihyperglycemic medication without any effects
There are effective methods that need to be followed while stopping antihyperglycemic medication. The first requirement is to stop it on the advice of the specialist treating the condition. One of the preconditions for stopping the medication is the ability or expectations of managing the condition through necessary changes. This could involve all of the following – dietary modifications, effective weight management program and adequate exercise. It needs to be borne in mind that these changes are not temporary in nature or for a transitionary period. These changes need to be incorporated as a way of life till the end of life. For instance, dietary modifications should become the new routine, while the amount of exercise may depend on age and the individual’s ability to take up exercises daily forever.
Weight management may also depend on various conditions, but it is necessary to ensure that weight is managed to an extent as is possible at all times. Prior to actually stopping antihyperglycemic medication, the treating specialist is likely to look at certain parameters to determine if it is safe to discontinue the medication. For instance, the individual is expected to have fasting blood glucose levels in the range of 80 to 130 mg/dL. The ideal random blood glucose levels are to be lesser than 180 mg/dL. Finally, hemoglobin levels are expected to be below 7%. These preconditions will typically also come with specific advice and recommendations from the treating specialist about the need for picking an appropriate exercise routine, and diet plan. Certain methods need to be put in place for monitoring progress and to seek support wherever necessary.
Education: Doctor of Physical Therapy (DPT) from New York University. Experience: 5 years of experience writing for physiotherapy and sports medicine blogs, providing expert insights on injury prevention and rehabilitation.
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