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Metformin vs. metformin ER: Differences, similarities, and which is better for you

Drug overview & main differences | Conditions treated | Efficacy | Insurance coverage and cost comparison | Side effects | Drug interactions | Warnings | FAQ

Metformin is a commonly prescribed medication used to treat type 2 diabetes mellitus. It is an antidiabetic agent that belongs to a class of drugs known as biguanides. It works by decreasing the glucose (blood sugar) production in the liver, decreasing glucose absorption in the intestines, and boosting insulin sensitivity. Metformin improves insulin sensitivity by increasing glucose uptake in the body’s tissues.

Type 2 diabetes mellitus is diagnosed when the body becomes resistant to the effects of insulin. Insulin is an essential hormone produced by the pancreas and used to transport glucose into the body’s cells for energy. When the body cannot use insulin properly, blood sugar levels rise which can cause damage to the blood vessels and nerves. Without proper treatment, diabetes can lead to complications and damage to organs such as the heart and kidneys.

Metformin is available in an immediate-release (IR) and extended-release (ER) form. While both forms of metformin contain the same active ingredient, they are taken in different ways. They also have some differences in side effects.

What are the main differences between metformin and metformin ER?

Metformin or metformin hydrochloride is the generic name for Glucophage. Immediate-release metformin is usually dosed as a 500 mg tablet taken twice daily with food. There is also an 850 mg tablet that can be taken once daily. The maximum dose of metformin is 2550 mg per day in divided doses. Metformin can treat type 2 diabetes in both adults and children.

Metformin ER is also known by the brand name Glucophage XR. It is the extended-release version of metformin and only needs to be taken once daily with food. The maximum total daily dose of metformin ER is 2000 mg. Unlike immediate-release metformin, metformin ER is only indicated for adults with type 2 diabetes. It also has fewer side effects and lasts longer than regular metformin.

RELATED: Metformin details | Metformin ER details

Main differences between metformin and metformin ER
Metformin Metformin ER
Drug class Biguanide Biguanide
Brand/generic status Generic version available Generic version available
What is the brand name? Glucophage Glucophage XR, Fortamet, Glumetza
What form(s) does the drug come in? Oral tablet Oral tablet, extended-release
What is the standard dosage? 500 mg twice daily or 850 mg once daily with meals 500 mg once daily with an evening meal
How long is the typical treatment? Long term for diabetes management Long term for diabetes management
Who typically uses the medication? Adults and children 10 years of age and older Adults 

Conditions treated by metformin and metformin ER

Both metformin and metformin ER are FDA-approved to manage type 2 diabetes mellitus. According to the American Diabetes Association (ADA), metformin is the first-line treatment for type 2 diabetes. In patients with an A1c less than 9% at the time of diagnosis, metformin should be started as monotherapy per the Standards of Medical Care in Diabetes. Metformin can help improve glycemic control and ultimately prevent complications that can arise from diabetes.

Not only can metformin be used to treat type 2 diabetes, but it can also be used for off-label purposes. Those with prediabetes and a high fasting plasma glucose (FPG) may be recommended metformin to prevent the onset of diabetes. Metformin is recommended when blood sugar levels are not managed with diet and exercise alone.

Metformin can also be used as an off-label option to treat gestational diabetes mellitus. This type of diabetes occurs in pregnant women who are predisposed to having diabetes. However, insulin is usually tried first.

Metformin has also been studied to treat polycystic ovary syndrome (POCS). This syndrome is characterized by an imbalance of sex hormones which can result in ovarian cysts, menstrual cycle changes, pregnancy issues, acne, and insulin resistance. Metformin can be prescribed to help decrease insulin resistance, decrease testosterone levels, and improve menstrual cycles as well as fertility.

The use of antipsychotic medications, such as olanzapine, risperidone, and clozapine, can lead to weight gain. According to some studies, Metformin has been shown to be effective for treating antipsychotic-induced weight gain. One review found that metformin helped reduce body mass index (BMI), body weight, and insulin resistance compared to placebo in those with antipsychotic-induced weight gain.

Condition Metformin Metformin ER
Type 2 diabetes mellitus management Yes Yes
Type 2 diabetes mellitus prevention Off-label Off-label
Gestational diabetes mellitus Off-label Off-label
Polycystic ovary syndrome Off-label Off-label
Weight gain due to antipsychotic therapy Off-label Off-label

Is metformin or metformin ER more effective?

Based on studies comparing metformin and metformin ER for type 2 diabetes mellitus, metformin ER has been found to be comparable to metformin in effectiveness. In fact, metformin ER may be superior to regular metformin based on its lower side-effects profile and ease of use. Those with type 2 diabetes mellitus may be more inclined to take a once-daily metformin pill instead of a twice-daily pill.

In one randomized, clinical study, metformin ER was found to be more effective than metformin IR when treating patients with type 2 diabetes. Those taking metformin ER experienced better glycemic control and lipid metabolism compared to metformin IR.

Another randomized, double-blind trial found that once-daily metformin ER had similar efficacy and safety to regular metformin. Additionally, the study noted an advantage of once-daily dosing with metformin ER. Both metformin and metformin ER improved HbA1c levels over 24 weeks in subjects who had never tried any other treatment for their diabetes.

Extended-release metformin may be preferred over immediate-release metformin. It has been shown to have better tolerability although it may be more expensive than immediate-release tablets. It’s important to consult medical advice from a healthcare professional when choosing a treatment option for type 2 diabetes mellitus.

Coverage and cost comparison of metformin vs. metformin ER

Metformin is the generic version of Glucophage. Generic metformin is covered by Medicare part D and most insurance plans. Brand-name Glucophage can be quite expensive and cost an average retail price above $150. This cost can be reduced by bringing a SingleCare discount card to the pharmacy. The metformin SingleCare card can bring the cost down to $4 for a 30-day supply of generic immediate-release metformin.

Almost all Medicare and insurance plans will cover generic metformin ER. Brand-name Glucophage XR can cost around $80 depending on the pharmacy you go to. With a SingleCare coupon card, generic metformin ER can be purchased for as low as $4 for a 30-day supply of once-daily metformin ER pills. Even with insurance, SingleCare may be able to offer a lower price. Check with your pharmacy to see if you can take advantage of a better discount with SingleCare.

Get the SingleCare prescription discount card

  Metformin Metformin ER
Typically covered by insurance? Yes Yes
Typically covered by Medicare? Yes Yes
Standard dosage 500 mg tablets (quantity of 60 tablets) 500 mg tablets (quantity of 30 tablets)
Typical Medicare copay $0-$8 $0-$8
SingleCare cost $4 $4

Common side effects of metformin vs. metformin ER

Metformin causes side effects that affect the gastrointestinal (GI) system. These side effects include diarrhea, nausea, vomiting, gas (flatulence), indigestion, and abdominal discomfort or stomach upset. Metformin IR also commonly causes fatigue or lack of energy (asthenia) as well as headaches.

Metformin ER has fewer side effects compared to metformin. The most common side effects associated with metformin ER are diarrhea, nausea, and vomiting. Metformin ER can also cause constipation in some people. Although metformin ER can cause other GI side effects such as indigestion and flatulence, these side effects do not occur as often compared to regular metformin.

Other side effects that can occur with metformin and metformin ER include dizziness, lightheadedness, and taste disturbances. Other more serious side effects of metformin and metformin ER include liver injury and hypoglycemia (low blood sugar).

  Metformin Metformin ER
Side Effect Applicable? Frequency Applicable? Frequency
Diarrhea Yes 53% Yes 10%
Nausea or vomiting Yes 26% Yes 7%
Flatulence Yes 12% Yes 1%-5%
Asthenia Yes 9% No
Indigestion Yes 7% Yes 1%-5%
Upset stomach Yes 6% Yes 1%-5%
Headache Yes 6% Yes 1%-5%
Constipation No Yes 1%-5%
Taste disturbance Yes 1%-5% Yes 1%-5%
Dizziness/lightheadedness Yes 1%-5% Yes 1%-5%

This may not be a complete list. Consult your doctor or pharmacist for possible side effects.
Source: DailyMed (Metformin), DailyMed (Metformin ER)

Drug interactions of metformin vs. metformin ER

Metformin and metformin ER can interact with several different medications. Drug interactions often result in blood glucose changes, an increased risk of lactic acidosis, or an accumulation of metformin in the blood which can increase the risk of adverse effects.

Taking metformin with drugs called carbonic anhydrase inhibitors can increase the risk of lactic acidosis, a potentially life-threatening condition from too much lactate in the body. These drugs include topiramate and acetazolamide among others.

Drugs like dolutegravir, cimetidine, and ranolazine can decrease the clearance of metformin. This can result in high levels of metformin in the blood and increase the risk of adverse events.

Other drugs like diuretics, corticosteroids, phenothiazines, estrogens, oral contraceptives, and calcium channel blockers can interfere with glucose control. Taking any of these medications with metformin may result in hyperglycemia (dangerously high blood sugar). Using insulin or a sulfonylurea or glinide drug with metformin can cause an increased risk of hypoglycemia.

Drug Drug Class Metformin Metformin ER
Topiramate
Acetazolamide
Zonisamide
Dichlorphenamide
Carbonic anhydrase inhibitors Yes Yes
Dolutegravir
Cimetidine
Vandetanib
Ranolazine
Drugs that decrease the clearance of metformin from the body Yes Yes
Insulin Insulin Yes Yes
Glimepiride
Glipizide
Glyburide
Repaglinide
Nateglinide
Insulin secretagogues Yes Yes
Hydrochlorothiazide
Chlorthalidone
Indapamide
Furosemide
Bumetanide
Torsemide
Ethacrynic acid
Diuretics Yes Yes
Prednisolone
Prednisone
Hydrocortisone Dexamethasone Fludrocortisone
Corticosteroids Yes Yes
Chlorpromazine
Mesoridazine
Prochlorperazine
Thioridazine
Phenothiazines Yes Yes
Levothyroxine Thyroid medications Yes Yes
Conjugated estrogens
Ethinyl estradiol
Levonorgestrel
Norethindrone
Desogestrel
Estrogens and oral contraceptives Yes Yes
Phenytoin Antiepileptic Yes Yes
Niacin Nicotinic acid Yes Yes
Ephedrine Sympathomimetic Yes Yes
Amlodipine
Diltiazem
Felodipine
Nicardipine
Nifedipine
Verapamil
Calcium channel blocker Yes Yes
Isoniazid Antibiotic Yes Yes

This may not be a complete list of all possible drug interactions. Consult a doctor with all the medications you may be taking.

Warnings of metformin vs. metformin ER

Metformin can cause lactic acidosis in rare cases. Lactic acidosis occurs when there is too much lactate in the blood. This condition can result in low blood pressure, hypothermia, and even death. Other symptoms of lactic acidosis include unusual weakness, diarrhea, stomach pain, and cramps. Seek immediate medical attention if you show these symptoms.

Metformin may decrease vitamin B12 levels in the body. Over time this can lead to vitamin B12 deficiency. Vitamin B12 levels should be monitored every 2 to 3 years when taking metformin long term.

Although rare, metformin may cause hypoglycemia if taken with insulin or an insulin secretagogue such as glipizide or repaglinide. In rare cases, metformin can cause hypoglycemia when taken with alcohol or an inadequate diet.

Frequently asked questions about metformin vs. metformin ER

What is metformin?

Metformin is a prescription medication approved to treat type 2 diabetes mellitus in adults and children aged 10 years and older. Immediate-release metformin is usually taken twice daily with meals. It is considered a first-line treatment for type 2 diabetes when combined with an appropriate diet and exercise routine.

What is metformin ER?

Metformin ER is the extended-release form of metformin. It is also known by the brand names Glucophage XR, Glumetza, or Fortamet. Metformin ER lasts longer than regular metformin and has less side effects. It is prescribed once daily with an evening meal.

Are metformin and metformin ER the same?

No. Metformin and metformin ER are not the same. Metformin is the immediate-release version while metformin ER is the extended-release version. Metformin is approved to treat type 2 diabetes in adults and children aged 10 years and older while metformin ER is only approved to treat type 2 diabetes in adults.

Is metformin and metformin ER better?

Metformin ER is considered to be a better option since it only needs to be taken once daily. It is similarly or more effective than metformin and is less likely to cause certain side effects.

Can I use metformin and metformin ER while pregnant?

Metformin may be used during pregnancy if the benefits outweigh the risks. Animal studies show that there are no harmful effects to the fetus. However, the risk of birth defects cannot be ruled out. Talk to a doctor to see if metformin is appropriate while pregnant or breastfeeding.

Can I use metformin and metformin ER with alcohol?

It is not generally recommended to take metformin or metformin ER with alcohol. Drinking alcohol may alter blood sugar levels resulting in an increased risk of hyperglycemia or hypoglycemia.

What does metformin HCl ER mean?

Metformin HCl ER contains metformin hydrochloride in an extended-release formulation.

Is metformin ER the same as Glucophage XR?

Metformin ER contains the same active ingredients as Glucophage XR. Metformin ER is the generic name for Glucophage XR.