Metformin vs. Metformin ER: Differences and similarities explained

In this article:

• What are the main differences between metformin and metformin ER?
• Conditions treated
• Is metformin or metformin ER more effective?
• Common side effects
• Coverage and cost comparison
• Drug interactions
• Drug warnings
• Frequently asked questions about metformin vs. metformin ER

In this article

• What are the main differences between metformin and metformin ER?
• Conditions treated
• Is metformin or metformin ER more effective?
• Common side effects
• Coverage and cost comparison
• Drug interactions
• Drug warnings
• Frequently asked questions about metformin vs. metformin ER

Metformin is a commonly prescribed medication used to treat Type 2 diabetes mellitus. It is an antihyperglycemic agent that belongs to a class of drugs known as biguanides. Metformin works by decreasing the glucose (blood sugar) production in the liver, decreasing glucose absorption in the intestines, and boosting insulin sensitivity. It is available in an immediate-release (IR) and extended-release (ER) form. While both forms of metformin contain the same active ingredient, they work differently and may cause different side effects. 

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What are the main differences between metformin and metformin ER?

Metformin is the generic name for Glucophage and Riomet. 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 2,550 mg per day in divided doses (825 mg three times a day). Metformin can treat Type 2 diabetes in both adults and children ages 10 and older. 

Metformin ER is also known by the brand name Glucophage XR, which has been discontinued in the U.S. 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 2,000 mg. Unlike immediate-release metformin, metformin ER is only indicated for adults with Type 2 diabetes, not children. It also has fewer side effects and lasts longer than regular metformin. 

RELATED: Metformin details | Metformin ER details

Compare the differences between metformin and metformin ER
Difference	Metformin	Metformin ER
Drug class	Biguanide	Biguanide
Brand/generic status	Generic version available	Generic version available
What is the brand name?	Brand: Glucophage	Brand: N/A
What form(s) does the drug come in?	Metformin: Oral tablets and oral solution Riomet: Oral solution	Extended-release oral tablets
What is the standard dosage?	Starting at 500 mg twice daily or 850 mg once daily, with a maximum of 2250 mg a day. Taken with meals	Starting at 500 mg once daily, with a maximum of 2000 mg 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 and older	Adults

Conditions treated by metformin and metformin ER

According to the American Diabetes Association (ADA), metformin is the first-line treatment for Type 2 diabetes when blood sugar levels are not controlled with diet and exercise alone. Although Type 2 diabetes is the only condition the Food and Drug Administration (FDA) has approved metformin to treat, it is sometimes prescribed off-label for other conditions. For example, people with prediabetes or a high fasting plasma glucose (FPG) may be recommended metformin to prevent the onset of diabetes. 

Metformin can also be used as an off-label option to treat gestational diabetes, which occurs in pregnant women whose glucose tolerance tests are high. However, insulin is usually tried first. 

Metformin has also been studied to treat polycystic ovary syndrome (PCOS). This syndrome is characterized by an imbalance of sex hormones, which can result in ovarian cysts, menstrual cycle changes, pregnancy issues, acne, hirsutism, and insulin resistance.  

According to some studies, metformin has been shown to be effective for treating weight gain from antipsychotic medications like olanzapine, risperidone, and clozapine. 

Compare metformin vs. metformin ER: Conditions treated
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, metformin ER has been found to be comparable to metformin in effectiveness. A randomized, double-blind trial found that once-daily metformin ER had similar efficacy and safety to regular metformin IR. Both metformin and metformin ER improved HbA1c levels over 24 weeks in subjects who had never tried any other treatment for their diabetes. 

However, 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 those taking metformin IR. 

Extended-release metformin may be preferred over immediate-release metformin. It has been shown to have better tolerability (less nausea and vomiting and gastrointestinal distress), and it may be easier for people to remember to take since it’s taken once daily. It’s important to consult medical advice from a healthcare professional when choosing a treatment option for Type 2 diabetes mellitus. 

Common side effects of metformin vs. metformin ER

Metformin IR 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. The immediate-release form of metformin 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 of metformin ER are diarrhea, nausea, and vomiting. Metformin ER can also cause constipation in some people. Metformin ER side effects don’t occur as often as regular metformin IR, although it can still cause GI side effects such as indigestion and flatulence. 

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

Compare metformin vs. metformin ER side effects
	Metformin (IR)	Metformin ER
Side effect	Frequency	Frequency
Diarrhea	53%	10%
Nausea or vomiting	26%	7%
Flatulence	12%	1%-5%
Asthenia	9%	–
Indigestion	7%	1%–5%
Upset stomach	6%	1%–5%
Headache	6%	1%–5%
Constipation	–	1%–5%
Taste disturbance	1%-5%	1%–5%
Dizziness/lightheadedness	1%-5%	1%–5%

This may not be a complete list. Consult your healthcare provider or pharmacist for possible side effects.

Source: DailyMed (Metformin), DailyMed (Metformin ER)

Coverage and cost comparison of metformin vs. metformin ER

Without insurance, the average cash price of Metformin is about $143 for 180, 1,000 mg tablets. A SingleCare coupon can reduce that price to $10.

Metformin ER costs an average of $62 for 90, 500 mg tablets without insurance. With a SingleCare coupon, you can pay as little as $4.

Metformin vs. metformin ER cost and coverage comparison
Coverage and cost	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)
SingleCare cost	$10 at Kroger	$4 at Walmart

Prescription drug prices often change. These are the most accurate medication prices at the time of publishing in ZIP code 23666 as of Jan. 6, 2026. The listed price without insurance references the price of brand-name drugs (unless otherwise specified). The listed SingleCare price references the price of generic drugs if available.

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 medications 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.    

Compare metformin and metformin ER drug interactions
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 healthcare provider about all the medications you may be taking before starting treatment with metformin. 

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 two to three 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 FDA 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. Metformin ER lasts longer than regular metformin and may be more tolerable in individuals who are sensitive to metformin side effects. It is prescribed once daily with an evening meal. 

Are metformin and metformin ER the same?

No. 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 ages 10 years and older, while metformin ER is only approved to treat Type 2 diabetes in adults. 

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 on the fetus. However, you should talk to your healthcare provider to see if metformin is safe for you 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. 

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, which has been discontinued in the U.S.