Metformin vs Metformin ER: An Overview of Differences

Metformin is an oral medication widely utilized to manage type 2 diabetes mellitus. It is a member of the biguanides class of drugs and works by limiting the liver's glucose production, reducing intestinal glucose absorption and enhancing insulin sensitivity. It achieves the latter by increasing glucose uptake by the body's tissues.

Type 2 diabetes mellitus is diagnosed when the body becomes resistant to insulin, a vital hormone that transmits glucose into the body's cells as energy. The inability to use insulin effectively results in elevated blood sugar levels, harming blood vessels and nerves. If left untreated, diabetes can lead to severe complications and damage vital organs such as the heart and kidneys. 

Metformin is available in two forms, immediate-release (IR) and extended-release (ER). Both forms have the same active ingredient, but the manner of administration and side effects differ. It is integral to consult a healthcare provider to determine the appropriate form and dosage.

Differences Between Metformin and Metformin ER

The main difference between metformin and metformin ER is in their formulations. Metformin is an immediate-release tablet, which means the medication is released into the bloodstream as soon as it is taken. On the other hand, metformin ER is an extended-release tablet, which means the medication is released slowly into the bloodstream over some time.

This difference in formulations can impact the medication's effectiveness and the way it is taken. For example, metformin ER is typically taken once a day, whereas regular metformin may need to be taken multiple times a day. It is designed to release the medication slowly into the body over a longer period of time, which may help reduce the incidence of gastrointestinal side effects.

However, it is important to note that individual responses can vary, and some people may experience side effects with metformin ER that they do not experience with regular metformin. Additionally, metformin ER may have a more gradual and sustained effect on blood sugar levels than regular metformin. Immediate-release metformin (IR) is the traditional form of the drug, which is taken two to three times a day, before or after meals.

It is usually the first line of treatment for people newly diagnosed with type 2 diabetes. IR metformin is generally well tolerated, but gastrointestinal side effects such as nausea, diarrhea, and abdominal discomfort are common and are usually more prominent during the initial weeks of therapy. These side effects improve with continued use and can often be minimized by starting at a low dose and gradually increasing it.

Another difference between the two is in dosage. The maximum daily dosage of metformin ER is 2000mg, whereas the dosage of regular metformin is 2550mg.

However, it is only sometimes recommended to increase the dosage of metformin to reach the maximum; it depends on a case-by-case basis. Metformin ER may also have a lower risk of causing side effects, such as gastrointestinal issues, compared to regular metformin.

This is because the extended-release formulation allows for a lower overall dose of the medication, which can reduce the risk of side effects. In summary, metformin and metformin ER are two forms of the same medication used to treat type 2 diabetes. However, they have different formulations, dosing, and potential side effects.  

What Are the Generic and Brand Versions of Metformin?

The generic version of metformin IR is called metformin hydrochloride. The brand-name version of metformin IR, Glucophage, is no longer available in the United States. There are also three generic versions of metformin ER tablets. These were developed from different brand-name medications and included Glucophage XR, Glumetza, and Fortamet.

Each of these versions may have slight differences in their formulation, and it is important to consult with your diabetes doctor or pharmacist before starting a medication. It is also worth noting that the liquid version of metformin ER (Riomet ER) is no longer available in the United States.

Metformin IR tablets are available in dosages of 500 mg, 850 mg, and 1,000 mg, while metformin IR oral liquid is available in a dosage of 500 mg/5 mL. Metformin ER tablets come in 500 mg and 750 mg, while Glumetza and Fortamet come in 500 mg and 1,000 mg.  

Conditions Treated By Metformin and Metformin ER.

Metformin and metformin ER are FDA-approved medications primarily used for treating type 2 diabetes mellitus. As per the American Diabetes Association (ADA), metformin is the first-line treatment for type 2 diabetes, and the Standards of Medical Care in Diabetes recommends initiation of metformin as monotherapy for patients with an A1c of less than 9% at the time of diagnosis.

Metformin improves glycemic control and reduces the risk of complications associated with diabetes. In addition to its primary use, metformin has also been used for off-label purposes. For individuals with diabetes and high fasting plasma glucose (FPG), metformin may be prescribed to prevent the onset of diabetes when blood sugar levels are not manageable through diet and exercise alone. Gestational diabetes mellitus is another condition that metformin is used to treat.

This type of diabetes occurs during pregnancy, and while insulin is considered the first line of treatment, metformin may be prescribed in certain cases. Metformin has also been studied as a viable treatment option for polycystic ovary syndrome (PCOS). This condition is characterized by hormonal imbalances that can lead to ovarian cysts, menstrual cycle changes, pregnancy issues, acne, and insulin resistance.

Metformin can help improve insulin sensitivity, reduce testosterone levels, and improve menstrual cycles and fertility. Lastly, metformin has been investigated as a treatment for antipsychotic-induced weight gain.

Studies have found metformin to be effective in reducing body mass index (BMI), body weight, and insulin resistance compared to a placebo in individuals experiencing weight gain as a side effect of antipsychotic medications such as olanzapine, risperidone, and clozapine.

It's important to note that while metformin and metformin ER have been investigated for off-label use, further studies are needed to understand their effectiveness and safety in treating these conditions. Consultation is essential in determining the most appropriate form and dosage of metformin for an individual's condition.

Is Metformin or Metformin ER More Effective?

Both types of metformin work by limiting the liver's glucose production, reducing intestinal glucose absorption and enhancing insulin sensitivity. This results in a decrease in overall blood sugar levels, thus improving long-term blood sugar control.

One key difference between the two forms of metformin is the manner of administration. Metformin is typically taken two or three times a day with meals, while metformin ER is taken once a day with an evening meal. This can be a convenient option for people who find it challenging to remember multiple daily doses. While both forms of metformin have been proven to be effective in managing blood sugar levels,

A systematic review of 14 randomized controlled trials suggests that metformin ER may have fewer gastrointestinal side effects compared to immediate-release metformin.

This may be because metformin ER releases the medication slowly into the body over a longer period of time, reducing the chance of a sudden spike in metformin levels that can lead to side effects. It's important to note that individual responses to medication can vary, and what works for one person may not work for another. Doctors will consider factors such as individual medical history, blood sugar levels, and other medications to decide which the most appropriate choice is.

Coverage and Cost Comparison of Metformin vs Metformin ER

When it comes to cost, generic metformin is typically more affordable than its brand-name counterpart, Glucophage. In fact, Medicare Part D and most insurance plans cover generic metformin. However, even with insurance coverage, the cost of brand-name Glucophage can still be relatively high, averaging at around $150 for a retail price.

To help offset this cost, many individuals turn to discount cards like SingleCare, which can reduce the price of generic immediate-release metformin to as low as $4 for a 30-day supply. The same is true for metformin ER, where insurance and Medicare often cover the generic version.

However, the retail price of brand-name Glucophage XR can be quite costly, averaging around $80. With the aid of a SingleCare coupon card, the cost of generic metformin ER can be brought down to as low as $4 for a 30-day supply. It is always recommended to check with your pharmacy and insurance plan to see if you qualify for any discounts or better prices.

Common Side Effects of Metformin vs Metformin ER

The common side effects of metformin are gastrointestinal in nature, such as nausea, diarrhea, and abdominal discomfort. These side effects occur in about 20-30% of people taking the medication and are usually more prominent during the initial weeks of therapy. They improve with continued use and can often be minimized by starting at a low dose and gradually increasing it.

Metformin ER has similar side effects, but they may be less common or less severe than with regular metformin. This is because the extended-release formulation is designed to release the medication slowly into the body over a longer period, which may help reduce gastrointestinal side effects. However, it's important to note that, as with any medication, individual responses can vary.

Some people may experience side effects with metformin ER that they do not experience with regular metformin. Another side effect that can occur with metformin is lactic acidosis, which is a rare but serious condition characterized by the buildup of lactic acid in the blood. This condition is more likely to occur in people with kidney or liver problems and those who have congestive heart failure.

If you have these conditions, your healthcare provider will likely monitor your kidney function regularly while you are taking metformin. The side effect profiles of metformin vs metformin ER are generally similar, and in most cases, both medications are well tolerated by people with type 2 diabetes. However, the gastrointestinal side effects may be less with Metformin ER. Report to the nearest health facility in case you experience severe side effects with medication.  

Drug Interactions of Metformin vs Metformin ER

Metformin and metformin extended-release (ER) are oral anti-diabetic medications used for the treatment of type 2 diabetes. Both medications decrease glucose production in the liver and increase insulin sensitivity. However, like all drugs, they have the potential to interact with other medications, leading to changes in blood glucose levels, an increased risk of lactic acidosis, or an accumulation of metformin in the bloodstream, which can increase the risk of adverse effects.

Metformin should be avoided in combination with carbonic anhydrase inhibitors such as topiramate, acetazolamide, and zonisamide, as it increases the risk of lactic acidosis, a serious and potentially life-threatening condition. Drugs that decrease the clearance of metformin, such as dolutegravir, cimetidine, and ranolazine, can result in high levels of metformin in the bloodstream and increase the risk of adverse effects.

Concomitant use of metformin with diuretics, corticosteroids, phenothiazines, estrogens, oral contraceptives, and calcium channel blockers can also interfere with glucose control and may result in hyperglycemia. Additionally, insulin, sulfonylurea, or glinide drugs with metformin can increase the risk of hypoglycemia. This may be a partial list of all possible drug interactions, and your diabetes doctor should be informed of all medications that you may be taking.

Warnings of Metformin vs Metformin ER

One significant warning with metformin is the risk of lactic acidosis, which is a rare but serious condition that occurs when there is an excessive buildup of lactate in the blood. Lactic acidosis is a metabolic disturbance that occurs when the body is unable to metabolize lactate fully, leading to a buildup of lactic acid in the bloodstream. It is a rare complication.

However, it can be fatal if not treated in time. The symptoms of lactic acidosis include low blood pressure, hypothermia, weakness, abdominal discomfort, nausea, and diarrhea. In severe cases, it can cause difficulty breathing, confusion, and even coma. It's crucial to seek medical attention immediately if experiencing any of these symptoms while taking metformin. Another warning is that metformin may decrease vitamin B12 levels in the body over time, resulting in a deficiency.

Vitamin B12 is important for properly functioning the brain and nervous system, red blood cells' formation and homocysteine metabolism. Metformin may interfere with vitamin B12 absorption by decreasing the amount of intrinsic factor, a protein needed for the absorption of vitamin B12. It's necessary to monitor vitamin B12 levels every 2-3 years when taking metformin long-term, especially in the elderly or in people with malabsorption syndromes.

Hypoglycemia, or low blood sugar, is another potential side effect of metformin when taken with other diabetes medications such as insulin or insulin secretagogue or with alcohol or inadequate diet. However, it is considered rare.

Metformin works by decreasing glucose production in the liver and increasing insulin sensitivity which can lead to a decrease in blood glucose levels; this effect can be enhanced when taken with other antidiabetic drugs. Therefore, it is important to monitor blood sugar levels and adjust dosages accordingly.

How Long Should You Take Metformin?

Metformin is a medication that is typically taken for the long-term management of type 2 diabetes. The duration of treatment with metformin can vary depending on an individual's specific needs and response to the medication. For many people with type 2 diabetes, metformin is a first-line therapy and is typically continued indefinitely. It has a good safety profile and can be effective in controlling blood sugar levels over the long term.

Additionally, metformin is also used as a long-term therapy for polycystic ovary syndrome (PCOS) and has been shown to be effective. However, the duration of treatment may change based on the patient's condition, the presence of any side effects, and the results of ongoing monitoring of the patient's blood glucose levels. In some cases, metformin may need to be stopped or its dosage adjusted if the patient experiences side effects or if the medication is no longer effective. It is important to regularly monitor your blood glucose levels and to reassess the need for metformin treatment as your condition changes.

How Long Does Metformin ER Last in Your System?

The half-life of metformin, the time it takes for half of the medication to be eliminated from the body, is approximately 6.2 to 17.6 hours. This can vary depending on various factors such as renal function and dosage. The extended-release (ER) formulation of metformin is designed to release the medication slowly over an extended period of time, typically 24 hours.

Therefore, the duration of action of metformin ER is longer than that of the immediate-release (IR) formulation. The duration of action of metformin ER can vary depending on the individual, but it is generally in the range of 24-48 hours. This means that after taking a single dose of metformin ER, the medication will remain active in your system for 24-48 hours.

Who shouldn't take metformin?

Metformin is a widely used medication for the treatment of type 2 diabetes. However, it may not be appropriate for everyone. People with certain health conditions or who take certain medications should not take metformin. Individuals with significant renal impairment or end-stage renal disease should avoid taking metformin. The medication is eliminated from the body by the kidneys, and in individuals with kidney problems, metformin can accumulate in the bloodstream and cause serious side effects.

If a person has a creatinine clearance (CrCl) of less than 60mL/min, they should not take metformin. Individuals with liver disease should also avoid taking metformin. As the liver plays a role in the metabolism and clearance of metformin, it can cause liver damage and liver failure if taken in high doses. Those who are in a state of metabolic acidosis, such as diabetic ketoacidosis, should not take metformin as it may lead to a worsening of the condition. Individuals with a known hypersensitivity to metformin or other components of the medication should not take it.

Prior consultation should be carried out if you are pregnant, breastfeeding or planning to become pregnant. As with any medication, it is important to inform your doctor of any current medications or supplements you are taking to avoid any potential drug interactions.

Frequently Asked Questions

What is Metformin?

Metformin is a medication used to help control type 2 diabetes. It works by lowering glucose levels in the body, which helps people to maintain healthy blood sugar levels. Metformin reduces the amount of glucose your liver produces and also helps your pancreas to produce less insulin, which can also help to reduce blood sugar levels.

What Is Metformin ER?

Metformin ER is a form of metformin that has been reformulated so that it can be taken by mouth once daily instead of twice daily, as per the original formulation. It is also available in long-acting and sustained release forms.

Are Metformin and Metformin ER the Same?

Metformin and metformin ER are not the same. Metformin acts on multiple systems in the body to help lower blood glucose levels. Metformin reduces insulin resistance, lowers triglycerides and cholesterol levels, reduces inflammation, improves blood vessel function, helps improve insulin sensitivity, and decreases total and LDL cholesterol. Metformin also has been shown to improve kidney function and reduce water retention in those with pre-existing high blood pressure.

Is Metformin or Metformin ER Better?

Both medications are used to treat type 2 diabetes, but metformin and metformin ER are different in how they work. Metformin helps lower blood glucose levels after meals by increasing insulin sensitivity in your body. This means your cells are more likely to respond to insulin rather than ignore it.

Metformin also reduces your body's production of glucose (sugar). The other medication, rosiglitazone, works in a similar way by reducing the amount of time your cells spend in the "fed" state — when they take up glucose from your blood.

Can I Use Metformin and Metformin ER While Pregnant?

Yes. In studies of pregnant women taking metformin without any other medications at all, it was safe to take this medicine during pregnancy. However, if your healthcare provider prescribes you this medicine while you are pregnant, you should check with your doctor first about any possible risks to your baby.   

About The Author 

Who is Dr. Ergin?  Dr. Ahmet Ergin is an endocrinologist interested in and passionate about diabetes care. Dr. Ergin earned his medical degree with honors at Marmara University School of Medicine in Istanbul, Turkey, and completed his internal medicine residency and endocrinology fellowship at Cleveland Clinic in Cleveland, Ohio.

He is a board-certified Internal Medicine, Endocrinology, Diabetes, and Metabolism Physician; a certified diabetes education specialist, the author of The Ultimate Diabetes Book; and the Founder of the SugarMD YouTube channel.  He practices in Port Saint Lucie, FL as an endocrinologist physician. Disclaimer: Any information on diseases and treatments on this website is for general guidance only and must never be a substitute for the advice your doctor or other qualified healthcare professional provides.  Always seek the advice of your physician, health provider, or other qualified healthcare professional’s advice with questions regarding your health.