Metformin

Generic name: metformin hydrochloride · Brand names: Glucophage, Riomet (oral solution, not covered here), Fortamet (ER, not covered here), Glumetza (ER, not covered here)

Quick facts

Drug class
Metformin is a biguanide.
Section
Label Highlights/Section 1; MedlinePlus Why is this medication prescribed?
Source text (exact source wording)
Metformin hydrochloride tablets are biguanide indicated as an adjunct to diet and exercise to improve glycemic control in adults and pediatric patients 10 years of age and older with type 2 diabetes mellitus. (1) / MedlinePlus: Metformin is in a class of drugs called biguanides.
Rx or otc
Rx (openFDA product_type for this set ID: HUMAN PRESCRIPTION DRUG; label: prescription medicines per Patient Information)
Forms and strengths
  • Metformin Hydrochloride Tablets USP 500 mg: white to off-white, round shaped, film-coated tablets debossed with the logo of "70" on one side and "Z" on the other side
  • Metformin Hydrochloride Tablets USP 850 mg: white to off-white, oval shaped, film-coated tablets debossed with the logo of "69" on one side and "Z" on the other side
  • Metformin Hydrochloride Tablets USP, 1,000 mg: white to off-white, oval shaped, biconvex, film-coated tablets with bisect on both the sides; one side of the bisect is debossed with "Z" and other side of the bisect is debossed with "71" (strengths as shown on the Zydus label; other manufacturers' labels also list 625 mg and 750 mg)
Generic available
Value
yes
Source
Chosen label is an ANDA generic (ANDA203686, Zydus Pharmaceuticals USA Inc.), openFDA record for set ID c82a10fa-1e8e-46b6-890a-737de3f34ee1
Common use one line
Used with diet and exercise to improve blood sugar control in adults and children 10 years of age and older with type 2 diabetes.

What it is used for

Metformin is used along with diet and exercise to help control blood sugar in adults and children 10 years of age and older who have type 2 diabetes. It is a generic of Glucophage.
Section
1 INDICATIONS AND USAGE
Source
DailyMed label, Zydus Pharmaceuticals USA Inc., set ID c82a10fa-1e8e-46b6-890a-737de3f34ee1
Source text (exact source wording)
1 INDICATIONS AND USAGE Metformin hydrochloride tablets are indicated as an adjunct to diet and exercise to improve glycemic control in adults and pediatric patients 10 years of age and older with type 2 diabetes mellitus.

How it works

Metformin lowers blood sugar. It lowers the sugar made by the liver, lowers the sugar absorbed from food in the intestine, and helps the body respond better to insulin.
Section
12.1 Mechanism of Action
Source
DailyMed label, Zydus Pharmaceuticals USA Inc., set ID c82a10fa-1e8e-46b6-890a-737de3f34ee1
Source text (exact source wording)
12.1 Mechanism of Action Metformin is an antihyperglycemic agent which improves glucose tolerance in patients with type 2 diabetes mellitus, lowering both basal and postprandial plasma glucose. Metformin decreases hepatic glucose production, decreases intestinal absorption of glucose, and improves insulin sensitivity by increasing peripheral glucose uptake and utilization. With metformin therapy, insulin secretion remains unchanged while fasting insulin levels and day-long plasma insulin response may decrease.

Dosage: adults

The usual starting dose is 500 mg twice a day or 850 mg once a day, taken with meals. The dose can be raised by 500 mg weekly or by 850 mg every 2 weeks, up to 2,550 mg per day in divided doses. Doses above 2,000 mg may be easier to tolerate taken 3 times a day with meals.
Section
2.1 Adult Dosage
Source
DailyMed label, Zydus Pharmaceuticals USA Inc., set ID c82a10fa-1e8e-46b6-890a-737de3f34ee1
Source text (exact source wording)
2.1 Adult Dosage Metformin Hydrochloride Tablets The recommended starting dose of metformin hydrochloride tablets are 500 mg orally twice a day or 850 mg once a day, given with meals. Increase the dose in increments of 500 mg weekly or 850 mg every 2 weeks on the basis of glycemic control and tolerability, up to a maximum dose of 2,550 mg per day, given in divided doses. Doses above 2,000 mg may be better tolerated given 3 times a day with meals.

Dosage: children

For children 10 years of age and older, the starting dose is 500 mg twice a day with meals. It can be raised by 500 mg weekly, up to 2,000 mg per day in two divided doses. Safety and effectiveness have not been established in children younger than 10 years old.
Section
2.2 Pediatric Dosage; 8.4 Pediatric Use
Source
DailyMed label, Zydus Pharmaceuticals USA Inc., set ID c82a10fa-1e8e-46b6-890a-737de3f34ee1
Source text (exact source wording)
2.2 Pediatric Dosage for Metformin Hydrochloride Tablets The recommended starting dose of metformin hydrochloride tablets for pediatric patients 10 years of age and older is 500 mg orally twice a day, given with meals. Increase dosage in increments of 500 mg weekly on the basis of glycemic control and tolerability, up to a maximum of 2,000 mg per day, given in divided doses twice daily. / 8.4 Pediatric Use ... Safety and effectiveness of metformin hydrochloride tablets have not been established in pediatric patients less than 10 years old.

Dosage adjustments

Drug interaction caps
Note
The label gives no dose cap tied to a specific interacting drug. Interaction guidance is in the interactions section.
Kidney
Kidney function is checked before starting metformin and from time to time after. Metformin is not to be used when eGFR is below 30 mL/minute/1.73 m2. Starting it is not recommended when eGFR is between 30 mL/minute/1.73 m2 and 45 mL/minute/1.73 m2. If eGFR later falls below 45 mL/min/1.73 m2, the benefit and risk of continuing are assessed. It is stopped if eGFR falls below 30 mL/minute/1.73 m2.
Section
2.3 Recommendations for Use in Renal Impairment
Source
DailyMed label, Zydus Pharmaceuticals USA Inc., set ID c82a10fa-1e8e-46b6-890a-737de3f34ee1
Source text (exact source wording)
2.3 Recommendations for Use in Renal Impairment Assess renal function prior to initiation of metformin hydrochloride tablets and periodically thereafter. Metformin hydrochloride tablets are contraindicated in patients with an estimated glomerular filtration rate (eGFR) below 30 mL/minute/1.73 m2. Initiation of metformin hydrochloride tablets in patients with an eGFR between 30 mL/minute/1.73 m2to 45 mL/minute/1.73 m2is not recommended. In patients taking metformin hydrochloride tablets whose eGFR later falls below 45 mL/min/1.73 m2, assess the benefit risk of continuing therapy. Discontinue metformin hydrochloride tablets if the patient's eGFR later falls below 30 mL/minute/1.73 m2 [ s ee Warnings and Precautions (5.1)].
Liver
Metformin is not recommended for people with liver problems because some cases of lactic acidosis have been linked to liver problems.
Section
8.7 Hepatic Impairment
Source
DailyMed label, Zydus Pharmaceuticals USA Inc., set ID c82a10fa-1e8e-46b6-890a-737de3f34ee1
Source text (exact source wording)
8.7 Hepatic Impairment Use of metformin in patients with hepatic impairment has been associated with some cases of lactic acidosis. Metformin hydrochloride tablets are not recommended in patients with hepatic impairment. [see Warnings and Precautions (5.1)].
Elderly
For older adults, dose choice should be careful and usually starts at the low end of the dosing range. Kidney function should be checked more often.
Section
8.5 Geriatric Use
Source
DailyMed label, Zydus Pharmaceuticals USA Inc., set ID c82a10fa-1e8e-46b6-890a-737de3f34ee1
Source text (exact source wording)
8.5 Geriatric Use Controlled clinical studies of metformin hydrochloride tablets did not include sufficient numbers of elderly patients to determine whether they respond differently from younger patients. In general, dose selection for an elderly patient should be cautious, usually starting at the low end of the dosing range, reflecting the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy and the higher risk of lactic acidosis. Assess renal function more frequently in elderly patients [see Warnings and Precautions (5.1)].

Missed dose

The label says to take your next dose as prescribed and not to take an extra dose the next day. MedlinePlus says to take a missed dose when you remember it, unless it is almost time for the next dose, and never to double up. These two sources differ, so ask your pharmacist or doctor.
Section
Patient Information (How should I take...); MedlinePlus What should I do if I forget a dose?
Source
Label and MedlinePlus, labeled separately in source_text
Conflict
yes
Conflict note
Label says take your next dose as prescribed; MedlinePlus says take the missed dose as soon as you remember unless it is almost time for the next dose. Both kept, not resolved.
Source text (exact source wording)
Label Patient Information: If you miss a dose of metformin hydrochloride tablets, take your next dose as prescribed unless your healthcare provider tells you differently. Do not take an extra dose the next day. // MedlinePlus: Take the missed dose as soon as you remember it. However, if it is almost time for the next dose, skip the missed dose and continue your regular dosing schedule. Do not take a double dose to make up for a missed one.

Overdose

Overdoses of more than 50 grams have happened. Lactic acidosis was reported in approximately 32% of overdose cases and low blood sugar in approximately 10%. If you take too much, call poison control at 1-800-222-1222, your healthcare provider, or go to the nearest hospital emergency room right away.
Section
10 OVERDOSAGE; Patient Information; MedlinePlus In case of emergency/overdose
Source
Label and MedlinePlus
Source text (exact source wording)
10 OVERDOSAGE Overdose of metformin hydrochloride has occurred, including ingestion of amounts greater than 50 grams. Hypoglycemia was reported in approximately 10% of cases, but no causal association with metformin has been established. Lactic acidosis has been reported in approximately 32% of metformin overdose cases [see Warnings and Precautions (5.1)]. Metformin is dialyzable with a clearance of up to 170 mL/min under good hemodynamic conditions. Therefore, hemodialysis may be useful for removal of accumulated drug from patients in whom metformin overdosage is suspected. // Patient Information: If you take too much metformin hydrochloride tablets, call your healthcare provider, local Poison Control Center, or go to the nearest hospital emergency room right away. // MedlinePlus: In case of overdose, call the poison control helpline at 1-800-222-1222.

Storage

Store at 20°C to 25°C (68°F to 77°F). MedlinePlus adds to keep it away from light, excess heat and moisture, and not in the bathroom.
Section
16.2 Storage; MedlinePlus storage
Source
Label and MedlinePlus
Labeler specific note
Zydus label wording; other labelers may differ.
Source text (exact source wording)
16.2 Storage Store at 20°C to 25°C (68°F to 77°F) [See USP Controlled Room Temperature]. Dispense in light-resistant containers. // MedlinePlus: Store it at room temperature and away from light, excess heat, and moisture (not in the bathroom).

Boxed warning

Metformin can rarely cause a serious and sometimes fatal build-up of lactic acid in the blood. Risk is higher with kidney problems, age 65 years or older, liver problems, heavy alcohol use, surgery, x-ray dye and some other conditions. If it is suspected, metformin is stopped right away and hospital care is needed.
Section
BOXED WARNING: WARNING: LACTIC ACIDOSIS (Full Prescribing Information)
Source
DailyMed label, Zydus Pharmaceuticals USA Inc., set ID c82a10fa-1e8e-46b6-890a-737de3f34ee1
Source text (exact source wording)
WARNING: LACTIC ACIDOSIS Postmarketing cases of metformin-associated lactic acidosis have resulted in death, hypothermia, hypotension, and resistant bradyarrhythmias. The onset of metformin- associated lactic acidosis is often subtle, accompanied only by nonspecific symptoms such as malaise, myalgias, respiratory distress, somnolence, and abdominal pain. Metformin- associated lactic acidosis was characterized by elevated blood lactate levels (>5 mmol/Liter), anion gap acidosis (without evidence of ketonuria or ketonemia), an increased lactate/pyruvate ratio; and metformin plasma levels generally >5 mcg/mL [see Warnings and Precautions (5.1)]. Risk factors for metformin-associated lactic acidosis include renal impairment, concomitant use of certain drugs (e.g. carbonic anhydrase inhibitors such as topiramate), age 65 years old or greater, having a radiological study with contrast, surgery and other procedures, hypoxic states (e.g., acute congestive heart failure), excessive alcohol intake, hepatic impairment, and mitochondrial diseases [see Warning and Precautions (5.1)]. Steps to reduce the risk of and manage metformin-associated lactic acidosis in these high risk groups are provided [see Dosage and Administration (2.3), Contraindications (4), Warnings and Precautions (5.1)]. If metformin-associated lactic acidosis is suspected, immediately discontinue metformin hydrochloride tablets and institute general supportive measures in a hospital setting. Prompt hemodialysis is recommended [see Warnings and Precautions (5.1)].

Contraindications

Severe kidney problems (eGFR below 30 mL/min/1.73 m2).
Section
4 CONTRAINDICATIONS
Source text (exact source wording)
Severe renal impairment (eGFR below 30 mL/min/1.73 m2) [see Warnings and Precautions (5.1)].
Allergy to metformin.
Section
4 CONTRAINDICATIONS
Source text (exact source wording)
Hypersensitivity to metformin.
Acute or chronic metabolic acidosis, including diabetic ketoacidosis.
Section
4 CONTRAINDICATIONS
Source text (exact source wording)
Acute or chronic metabolic acidosis, including diabetic ketoacidosis, with or without coma.

Warnings and precautions

Lactic acidosis is rare but serious. Symptoms can be vague, such as malaise, muscle pain, belly pain, trouble breathing or unusual sleepiness. Risk goes up with kidney problems, age 65 or greater, contrast dye, surgery, low-oxygen states such as acute heart failure, excessive alcohol, liver problems and mitochondrial diseases. Get an eGFR before starting and at least annually.
Heading
5.1 Lactic Acidosis
Source text (exact source wording)
There have been postmarketing cases of metformin-associated lactic acidosis, including fatal cases. These cases had a subtle onset and were accompanied by nonspecific symptoms such as malaise, myalgias, abdominal pain, respiratory distress, or increased somnolence; however, hypotension and resistant bradyarrhythmias have occurred with severe acidosis. Metformin- associated lactic acidosis was characterized by elevated blood lactate concentrations (>5 mmol/L), anion gap acidosis (without evidence of ketonuria or ketonemia), and an increased lactate: pyruvate ratio; metformin plasma levels were generally >5 mcg/mL. Metformin decreases liver uptake of lactate increasing lactate blood levels which may increase the risk of lactic acidosis, especially in patients at risk. If metformin-associated lactic acidosis is suspected, general supportive measures should be instituted promptly in a hospital setting, along with immediate discontinuation of metformin hydrochloride tablets. In metformin hydrochloride tablets treated patients with a diagnosis or strong suspicion of lactic acidosis, prompt hemodialysis is recommended to correct the acidosis and remove accumulated metformin (metformin hydrochloride is dialyzable with a clearance of up to 170 mL/min under good hemodynamic conditions). Hemodialysis has often resulted in reversal of symptoms and recovery. Educate patients and their families about the symptoms of lactic acidosis and, if these symptoms occur, instruct them to discontinue metformin hydrochloride tablets and report these symptoms to their healthcare provider. For each of the known and possible risk factors for metformin-associated lactic acidosis, recommendations to reduce the risk of and manage metformin-associated lactic acidosis are provided below: Renal impairment The postmarketing metformin-associated lactic acidosis cases primarily occurred in patients with significant renal impairment. The risk of metformin accumulation and metformin-associated lactic acidosis increases with the severity of renal impairment because metformin is substantially excreted by the kidney. Clinical recommendations based upon the patient's renal function include [see Dosage and Administration (2.1), Clinical Pharmacology (12.3)]: Before initiating metformin hydrochloride tablets, obtain an estimated glomerular filtration rate (eGFR). Metformin hydrochloride tablets are contraindicated in patients with an eGFR less than 30 mL/min/1.73 m2 [see Contraindications (4)]. Initiation of metformin hydrochloride tablets is not recommended in patients with eGFR between 30 mL/min/1.73 m2to 45 mL/min/1.73 m2. Obtain an eGFR at least annually in all patients taking metformin hydrochloride tablets. In patients at risk for the development of renal impairment (e.g., the elderly), renal function should be assessed more frequently. In patients taking metformin hydrochloride tablets whose eGFR falls below 45 mL/min/1.73 m2, assess the benefit and risk of continuing therapy. Drug interactions The concomitant use of metformin hydrochloride tablets with specific drugs may increase the risk of metformin-associated lactic acidosis: those that impair renal function, result in significant hemodynamic change, interfere with acid-base balance, or increase metformin accumulation. Consider more frequent monitoring of patients. Age 65 or greater The risk of metformin-associated lactic acidosis increases with the patient's age because elderly patients have a greater likelihood of having hepatic, renal, or cardiac impairment than younger patients. Assess renal function more frequently in elderly patients. Radiologic studies with contrast Administration of intravascular iodinated contrast agents in metformin-treated patients has led to an acute decrease in renal function and the occurrence of lactic acidosis. Stop metformin hydrochloride tablets at the time of, or prior to, an iodinated contrast imaging procedure in patients with an eGFR between 30 mL/min/1.73 m2 and 60 mL/min/1.73 m2; in patients with a history of hepatic impairment, alcoholism or heart failure; or in patients who will be administered intra-arterial iodinated contrast. Re-evaluate eGFR 48 hours after the imaging procedure, and restart metformin hydrochloride tablets if renal function is stable. Surgery and other procedures Withholding of food and fluids during surgical or other procedures may increase the risk for volume depletion, hypotension, and renal impairment. Metformin hydrochloride tablets should be temporarily discontinued while patients have restricted food and fluid intake. Hypoxic states Several of the postmarketing cases of metformin-associated lactic acidosis occurred in the setting of acute congestive heart failure (particularly when accompanied by hypoperfusion and hypoxemia). Cardiovascular collapse (shock), acute myocardial infarction, sepsis, and other conditions associated with hypoxemia have been associated with lactic acidosis and may cause prerenal azotemia. When such an event occurs, discontinue metformin hydrochloride tablets. Excessive alcohol intake Alcohol potentiates the effect of metformin on lactate metabolism. Patients should be warned against excessive alcohol intake while receiving metformin hydrochloride tablets. Hepatic impairment Patients with hepatic impairment have developed cases of metformin-associated lactic acidosis. This may be due to impaired lactate clearance resulting in higher lactate blood levels. Therefore, avoid use of metformin hydrochloride tablets in patients with clinical or laboratory evidence of hepatic disease. Mitochondrial Diseases Metformin may increase the risk of lactic acidosis in patients with mitochondrial diseases such as mitochondrial encephalomyopathy with lactic acidosis, and stroke-like episodes (MELAS) syndrome and maternally inherited diabetes and deafness (MIDD). Metformin hydrochloride tablets are not recommended in patients with mitochondrial diseases such as MELAS syndrome and MIDD. If a patient taking metformin hydrochloride tablets develops elevated lactic acid levels (with or without accompanying neurologic signs and symptoms), discontinue metformin hydrochloride tablets. Depending on the clinical context, consider evaluating the patient for MELAS, MIDD, or other mitochondrial disease.
In trials of 29 week duration, about 7% of patients had vitamin B12 levels drop below normal. Blood counts are measured every year and vitamin B12 every 2 to 3 years.
Heading
5.2 Vitamin B12 Deficiency
Source text (exact source wording)
In metformin hydrochloride tablets clinical trials of 29 week duration, a decrease to subnormal levels of previously normal serum vitamin B12 levels was observed in approximately 7% of patients. Such decrease, possibly due to interference with B12 absorption from the B12-intrinsic factor complex, may be associated with anemia but appears to be rapidly reversible with discontinuation of Metformin hydrochloride tablets or vitamin B12 supplementation. Certain individuals (those with inadequate vitamin B12 or calcium intake or absorption) appear to be predisposed to developing subnormal vitamin B12 levels. Measure hematologic parameters on an annual basis and vitamin B12 at 2 to 3 year intervals in patients on metformin hydrochloride tablets and manage any abnormalities [see Adverse Reactions (6.1)].
Metformin may increase the risk of low blood sugar when combined with insulin or a sulfonylurea. A lower dose of the insulin or sulfonylurea may be needed.
Heading
5.3 Hypoglycemia with Concomitant Use with Insulin and Insulin Secretagogues
Source text (exact source wording)
Insulin and insulin secretagogues (e.g., sulfonylurea) are known to cause hypoglycemia. Metformin hydrochloride tablets may increase the risk of hypoglycemia when combined with insulin and/or an insulin secretagogue. Therefore, a lower dose of insulin or insulin secretagogue may be required to minimize the risk of hypoglycemia when used in combination with metformin hydrochloride tablets [see Drug Interactions (7)].
No clinical studies have shown conclusive proof that metformin lowers the risk of large blood vessel problems.
Heading
5.4 Macrovascular Outcomes
Source text (exact source wording)
There have been no clinical studies establishing conclusive evidence of macrovascular risk reduction with metformin hydrochloride tablets.

Pregnancy and breastfeeding

Limited data are not enough to say whether metformin raises the risk of major birth defects or miscarriage. Poorly controlled diabetes in pregnancy carries its own risks. Metformin is present in human milk, and there is not enough information to know its effects on a breastfed baby. Metformin may cause ovulation in some women who had not been ovulating, which can lead to unintended pregnancy. MedlinePlus says to tell your doctor if you are pregnant, plan to become pregnant, or are breastfeeding.
Section
8.1 Pregnancy, 8.2 Lactation, 8.3 Females and Males of Reproductive Potential
Source
DailyMed label, Zydus Pharmaceuticals USA Inc., set ID c82a10fa-1e8e-46b6-890a-737de3f34ee1
Source text (exact source wording)
8.1 Pregnancy Risk Summary Limited data with metformin hydrochloride tablets in pregnant women are not sufficient to determine a drug-associated risk for major birth defects or miscarriage. Published studies with metformin use during pregnancy have not reported a clear association with metformin and major birth defect or miscarriage risk [see Data]. There are risks to the mother and fetus associated with poorly controlled diabetes mellitus in pregnancy [see Clinical Considerations]. No adverse developmental effects were observed when metformin was administered to pregnant Sprague Dawley rats and rabbits during the period of organogenesis at doses up to 2 times and 5 times, respectively, a 2,550 mg clinical dose, based on body surface area [see Data]. The estimated background risk of major birth defects is 6% to 10% in women with pre-gestational diabetes mellitus with an HbA1C >7 and has been reported to be as high as 20% to 25% in women with a HbA1C >10. The estimated background risk of miscarriage for the indicated population is unknown. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively. Clinical Considerations Disease-associated maternal and/or embryo/fetal risk Poorly-controlled diabetes mellitus in pregnancy increases the maternal risk for diabetic ketoacidosis, pre-eclampsia, spontaneous abortions, preterm delivery, stillbirth and delivery complications. Poorly controlled diabetes mellitus increases the fetal risk for major birth defects, stillbirth, and macrosomia related morbidity. 8.2 Lactation Risk Summary Limited published studies report that metformin is present in human milk [see Data]. However, there is insufficient information to determine the effects of metformin on the breastfed infant and no available information on the effects of metformin on milk production. Therefore, the developmental and health benefits of breastfeeding should be considered along with the mother's clinical need for metformin hydrochloride tablets and any potential adverse effects on the breastfed child from metformin hydrochloride tablets or from the underlying maternal condition. 8.3 Females and Males of Reproductive Potential Discuss the potential for unintended pregnancy with premenopausal women as therapy with metformin hydrochloride tablets may result in ovulation in some anovulatory women.

Side effects

Common
In the label's trial, the reactions seen in more than 5% of people and more often than with placebo were diarrhea (53%), nausea/vomiting (26%), flatulence (12%), asthenia (9%), indigestion (7%), abdominal discomfort (6%) and headache (6%).
Threshold
Adverse reactions reported in greater than 5% of metformin hydrochloride tablets treated patients and more common than placebo (Table 1, 6.1 Clinical Studies Experience)
Section
6.1 Clinical Studies Experience, Table 1
Source
DailyMed label, Zydus Pharmaceuticals USA Inc., set ID c82a10fa-1e8e-46b6-890a-737de3f34ee1
Source text (exact source wording)
Adverse reactions reported in greater than 5% of metformin hydrochloride tablets treated patients and that were more common than in placebo-treated patients, are listed in Table 1. Table 1 Adverse Reactions from a Clinical Trial of Metformin Hydrochloride Tablets Occurring >5% and More Common than Placebo in Patients with Type 2 Diabetes Mellitus (Metformin Hydrochloride Tablets n=141; Placebo n=145): Diarrhea 53% vs 12%; Nausea/Vomiting 26% vs 8%; Flatulence 12% vs 6%; Asthenia 9% vs 6%; Indigestion 7% vs 4%; Abdominal Discomfort 6% vs 5%; Headache 6% vs 5%.
Less common
Reactions seen in at least 1% up to 5% of patients and more often than placebo were abnormal stools, hypoglycemia, myalgia, lightheaded, dyspnea, nail disorder, rash, sweating increased, taste disorder, chest discomfort, chills, flu syndrome, flushing and palpitation.
Section
6.1 Clinical Studies Experience
Source
DailyMed label, Zydus Pharmaceuticals USA Inc., set ID c82a10fa-1e8e-46b6-890a-737de3f34ee1
Note
The label gives this list without individual percentages, only the range of at least 1% up to 5%.
Source text (exact source wording)
Additionally, the following adverse reactions were reported in ≥1% to ≤5% of metformin hydrochloride tablets treated patients and were more commonly reported with metformin hydrochloride tablets than placebo: abnormal stools, hypoglycemia, myalgia, lightheaded, dyspnea, nail disorder, rash, sweating increased, taste disorder, chest discomfort, chills, flu syndrome, flushing, palpitation. Pediatric Patients In clinical trials with metformin hydrochloride tablets in pediatric patients with type 2 diabetes mellitus, the profile of adverse reactions was similar to that observed in adults.
Serious
From the label: lactic acidosis, low vitamin B12 (about 7% of patients), low blood sugar when combined with insulin or a sulfonylurea, and liver injury reported after approval. MedlinePlus says to call your doctor right away for chest pain, extreme tiredness or weakness, nausea, vomiting, stomach pain, decreased appetite, deep and rapid breathing, dizziness, fast or slow heartbeat, muscle pain, or feeling cold in your hands or feet.
Label
Section
5.1, 5.2, 5.3, 6.2
Source
DailyMed label, Zydus Pharmaceuticals USA Inc., set ID c82a10fa-1e8e-46b6-890a-737de3f34ee1
Source text (exact source wording)
5.1 Lactic Acidosis (see Boxed Warning and Warnings and Precautions). 5.2 Vitamin B12 Deficiency: a decrease to subnormal levels of previously normal serum vitamin B12 levels was observed in approximately 7% of patients. 5.3 Hypoglycemia with Concomitant Use with Insulin and Insulin Secretagogues. 6.2 Postmarketing Experience: Cholestatic, hepatocellular, and mixed hepatocellular liver injury have been reported with postmarketing use of metformin.
Medlineplus
Section
What side effects can this medication cause? / IMPORTANT WARNING
Source
MedlinePlus Metformin (a696005)
Source text (exact source wording)
Some side effects can be serious. If you experience any of these symptoms or those listed in the IMPORTANT WARNING section, call your doctor immediately or get emergency treatment: chest pain. If you experience any of the following symptoms, stop taking metformin and call your doctor immediately: extreme tiredness, weakness, or discomfort; nausea; vomiting; stomach pain; decreased appetite; deep and rapid breathing or shortness of breath; dizziness; lightheadedness; fast or slow heartbeat; muscle pain; or feeling cold, especially in your hands or feet.
Led to discontinuation
Diarrhea led 6% of patients to stop taking metformin.
Section
6.1 Clinical Studies Experience
Source
DailyMed label, Zydus Pharmaceuticals USA Inc., set ID c82a10fa-1e8e-46b6-890a-737de3f34ee1
Source text (exact source wording)
Diarrhea led to discontinuation of metformin hydrochloride tablets in 6% of patients.

Interactions

Drugs
Topiramate, zonisamide, acetazolamide and dichlorphenamide can raise the chance of lactic acidosis when taken with metformin. The label says these patients should be watched more often.
Name
Carbonic anhydrase inhibitors
Section
7 DRUG INTERACTIONS, Table 3
Source
DailyMed label, Zydus Pharmaceuticals USA Inc., set ID c82a10fa-1e8e-46b6-890a-737de3f34ee1
Source text (exact source wording)
Carbonic anhydrase inhibitors frequently cause a decrease in serum bicarbonate and induce non-anion gap, hyperchloremic metabolic acidosis. Concomitant use of these drugs with metformin hydrochloride tablets may increase the risk for lactic acidosis. Intervention: Consider more frequent monitoring of these patients. Examples: Topiramate, zonisamide, acetazolamide or dichlorphenamide.
Ranolazine, vandetanib, dolutegravir and cimetidine can cause more metformin to stay in the body, which may raise the chance of lactic acidosis. The label says to weigh the benefits and risks of using them together.
Name
Drugs that reduce metformin clearance
Section
7 DRUG INTERACTIONS, Table 3
Source
DailyMed label, Zydus Pharmaceuticals USA Inc., set ID c82a10fa-1e8e-46b6-890a-737de3f34ee1
Source text (exact source wording)
Concomitant use of drugs that interfere with common renal tubular transport systems involved in the renal elimination of metformin (e.g., organic cationic transporter-2 [OCT2] / multidrug and toxin extrusion [MATE] inhibitors) could increase systemic exposure to metformin and may increase the risk for lactic acidosis [see Clinical Pharmacology (12.3)]. Intervention: Consider the benefits and risks of concomitant use with metformin hydrochloride tablets. Examples: Ranolazine, vandetanib, dolutegravir, and cimetidine.
Taking metformin with insulin or a sulfonylurea may raise the chance of low blood sugar. These patients may need lower doses of the insulin or sulfonylurea.
Name
Insulin secretagogues or insulin
Section
7 DRUG INTERACTIONS, Table 3
Source
DailyMed label, Zydus Pharmaceuticals USA Inc., set ID c82a10fa-1e8e-46b6-890a-737de3f34ee1
Source text (exact source wording)
Coadministration of metformin hydrochloride tablets with an insulin secretagogue (e.g., sulfonylurea) or insulin may increase the risk of hypoglycemia. Intervention: Patients receiving an insulin secretagogue or insulin may require lower doses of the insulin secretagogue or insulin.
Some drugs raise blood sugar and can make diabetes harder to control. The label lists thiazides and other diuretics, corticosteroids, phenothiazines, thyroid products, estrogens, oral contraceptives, phenytoin, nicotinic acid, sympathomimetics, calcium channel blockers, and isoniazid as examples. Blood sugar should be watched closely when these are started or stopped.
Name
Drugs affecting glycemic control
Section
7 DRUG INTERACTIONS, Table 3
Source
DailyMed label, Zydus Pharmaceuticals USA Inc., set ID c82a10fa-1e8e-46b6-890a-737de3f34ee1
Source text (exact source wording)
Certain drugs tend to produce hyperglycemia and may lead to loss of glycemic control. Intervention: When such drugs are administered to a patient receiving metformin hydrochloride tablets, observe the patient closely for loss of blood glucose control. When such drugs are withdrawn from a patient receiving metformin hydrochloride tablets, observe the patient closely for hypoglycemia. Examples: Thiazides and other diuretics, corticosteroids, phenothiazines, thyroid products, estrogens, oral contraceptives, phenytoin, nicotinic acid, sympathomimetics, calcium channel blockers, and isoniazid.
Food and alcohol
Alcohol makes metformin's effect on lactate stronger. Patients are warned not to drink too much alcohol.
Name
Alcohol
Section
7 DRUG INTERACTIONS, Table 3
Source
DailyMed label, Zydus Pharmaceuticals USA Inc., set ID c82a10fa-1e8e-46b6-890a-737de3f34ee1
Source text (exact source wording)
Alcohol is known to potentiate the effect of metformin on lactate metabolism. Intervention: Warn patients against excessive alcohol intake while receiving metformin hydrochloride tablets.
MedlinePlus says drinking alcohol raises the risk of lactic acidosis and may lower blood sugar, and to ask your doctor how much alcohol is safe.
Name
Alcohol (MedlinePlus)
Section
IMPORTANT WARNING
Source
MedlinePlus Metformin (a696005)
Source text (exact source wording)
Drinking alcohol increases your risk of developing lactic acidosis or may cause a decrease in blood sugar. Ask your doctor how much alcohol is safe to drink while you are taking metformin.
Name
Grapefruit
Section
not in cited sources
Source
DailyMed label, Zydus Pharmaceuticals USA Inc., set ID c82a10fa-1e8e-46b6-890a-737de3f34ee1
Other
Metformin may need to be stopped at the time of, or before, an x-ray procedure that uses iodinated dye, depending on kidney function, liver disease, alcoholism, heart failure or the type of dye. Kidney function is re-checked 48 hours after the procedure, and metformin is restarted if it is stable.
Name
Iodinated contrast imaging (x-ray dye)
Section
2.4 Discontinuation for Iodinated Contrast Imaging Procedures
Source
DailyMed label, Zydus Pharmaceuticals USA Inc., set ID c82a10fa-1e8e-46b6-890a-737de3f34ee1
Source text (exact source wording)
Discontinue metformin hydrochloride tablets at the time of, or prior to, an iodinated contrast imaging procedure in patients with an eGFR between 30 mL/min/1.73 m2 and 60 mL/min/1.73 m2; in patients with a history of liver disease, alcoholism, or heart failure; or in patients who will be administered intra- arterial iodinated contrast. Re-evaluate eGFR 48 hours after the imaging procedure; restart metformin hydrochloride tablets if renal function is stable.

Patient tips

Take it with meals to help with stomach upset and swallow the tablets whole. Do not drink a lot of alcohol. Stop it and call your provider right away for symptoms of lactic acidosis such as feeling very weak and tired, unusual muscle pain, trouble breathing, unusual sleepiness, or feeling cold, dizzy or lightheaded. Common side effects are diarrhea, nausea and upset stomach and usually go away; call your doctor if they bother you a lot or last more than a few weeks. About 3 out of every 100 people notice a metallic taste when they start. Keep taking it even if you feel well and do not stop without talking to your doctor.
Label patient information
Section
Patient Information
Source
DailyMed label, Zydus Pharmaceuticals USA Inc., set ID c82a10fa-1e8e-46b6-890a-737de3f34ee1
Source text (exact source wording)
Metformin hydrochloride tablets should be taken with meals to help lessen an upset stomach side effect. Swallow metformin hydrochloride tablets whole. You may sometimes pass a soft mass in your stools (bowel movement) that looks like metformin hydrochloride tablets. What should I avoid while taking metformin hydrochloride tablets? Do not drink a lot of alcoholic drinks while taking metformin hydrochloride tablets. This means you should not binge drink for short periods, and you should not drink a lot of alcohol on a regular basis. Alcohol can increase the chance of getting lactic acidosis. Stop taking metformin hydrochloride tablets and call your healthcare provider right away if you get any of the following symptoms of lactic acidosis: feel very weak and tired have unusual (not normal) muscle pain have trouble breathing have unusual sleepiness or sleep longer than usual have unexplained stomach or intestinal problems with nausea and vomiting, or diarrhea feel cold, especially in your arms and legs feel dizzy or lightheaded have a slow or irregular heartbeat Common side effects of metformin hydrochloride tablets include diarrhea, nausea, and upset stomach. These side effects generally go away after you take the medicine for a while. Taking your medicine with meals can help reduce these side effects. Tell your doctor if the side effects bother you a lot, last for more than a few weeks, come back after they've gone away, or start later in therapy. You may need a lower dose or need to stop taking the medicine for a short period or for good. About 3 out of every 100 people who take metformin hydrochloride tablets have an unpleasant metallic taste when they start taking the medicine. It lasts for a short time. Check your blood sugar as your healthcare provider tells you to. Stay on your prescribed diet and exercise program while taking metformin hydrochloride tablets.
Medlineplus
Section
MedlinePlus (How should this medicine be used? / What special precautions...)
Source
MedlinePlus Metformin (a696005)
Source text (exact source wording)
Metformin controls diabetes but does not cure it. Continue to take metformin even if you feel well. Do not stop taking metformin without talking to your doctor. Tell your doctor if you regularly drink alcohol or sometimes drink large amounts of alcohol in a short time (binge drinking). tell your doctor if you eat less or exercise more than usual. This can affect your blood sugar. Your doctor will give you instructions if this happens. Keep all appointments with your doctor and the laboratory. Your doctor will order certain tests before and during treatment to check how well your kidneys are working and your body's response to metformin.

Alternatives

Indication source
Label Section 1: type 2 diabetes mellitus

Frequently asked questions

Question
What is metformin used for?
Answer
Metformin is used along with diet and exercise to help control blood sugar in adults and children 10 years of age and older who have type 2 diabetes. It is not for people with type 1 diabetes.
Source section
1 INDICATIONS AND USAGE; Patient Information (What are metformin hydrochloride tablets?)
Source
DailyMed label, Zydus Pharmaceuticals USA Inc., set ID c82a10fa-1e8e-46b6-890a-737de3f34ee1
Question
Should I take metformin with food?
Answer
Yes. The label says to take it with meals to help lessen an upset stomach, and to swallow the tablets whole.
Source section
Patient Information (How should I take...); 2.1
Source
DailyMed label, Zydus Pharmaceuticals USA Inc., set ID c82a10fa-1e8e-46b6-890a-737de3f34ee1
Question
What if I miss a dose?
Answer
The label says to take your next dose as prescribed and not to take an extra dose the next day. MedlinePlus says to take the missed dose when you remember it unless it is almost time for the next dose, and never to take a double dose. The two sources differ, so ask your pharmacist or doctor.
Source section
Patient Information; MedlinePlus What should I do if I forget a dose?
Source
Label and MedlinePlus
Question
Can I drink alcohol on metformin?
Answer
Do not drink a lot of alcohol. Alcohol can increase the chance of getting lactic acidosis. MedlinePlus says to ask your doctor how much alcohol is safe.
Source section
Patient Information (What should I avoid...); 7 DRUG INTERACTIONS; MedlinePlus IMPORTANT WARNING
Source
Label and MedlinePlus
Question
What are the common side effects?
Answer
In the label's trial, the most common reactions (more than 5% of people and more than placebo) were diarrhea, nausea/vomiting, flatulence, asthenia, indigestion, abdominal discomfort and headache. Diarrhea was the most common at 53%. The Patient Information says these stomach side effects generally go away after a while and that taking the medicine with meals can help.
Source section
6.1 Table 1; Patient Information
Source
DailyMed label, Zydus Pharmaceuticals USA Inc., set ID c82a10fa-1e8e-46b6-890a-737de3f34ee1
Question
Is metformin safe in pregnancy or while breastfeeding?
Answer
Limited data are not enough to say whether metformin raises the risk of major birth defects or miscarriage. Metformin is present in human milk, and there is not enough information to know its effects on a breastfed baby. Talk with your healthcare provider about the best plan.
Source section
8.1 Pregnancy; 8.2 Lactation
Source
DailyMed label, Zydus Pharmaceuticals USA Inc., set ID c82a10fa-1e8e-46b6-890a-737de3f34ee1
Question
What should I not combine with metformin?
Answer
The label lists carbonic anhydrase inhibitors (topiramate, zonisamide, acetazolamide, dichlorphenamide), drugs that reduce metformin clearance (ranolazine, vandetanib, dolutegravir, cimetidine), insulin or sulfonylureas, and drugs that raise blood sugar. These are not all banned, but they can need closer monitoring or a different dose. Always tell your provider and pharmacist about everything you take.
Source section
7 DRUG INTERACTIONS, Table 3
Source
DailyMed label, Zydus Pharmaceuticals USA Inc., set ID c82a10fa-1e8e-46b6-890a-737de3f34ee1
Question
Should I stop taking metformin when I feel well?
Answer
No. MedlinePlus says metformin controls diabetes but does not cure it, to keep taking it even if you feel well, and not to stop without talking to your doctor.
Source section
How should this medicine be used?
Source
MedlinePlus Metformin (a696005)

Sources

  • DailyMed label, Zydus Pharmaceuticals USA Inc. metformin hydrochloride tablet, film coated (ANDA203686)
    Set id: c82a10fa-1e8e-46b6-890a-737de3f34ee1 · Label effective or revised date: Revised: 7/2026 (label shows 'Rev.: 07/26'; DailyMed shows 'Updated July 15, 2026') · Dailymed version date: DailyMed list published_date Aug 17, 2026; SPL effectiveTime 2026-07-15 · Fetched at: 2026-11-02 · Sections used: Boxed Warning, 1, 2, 3, 4, 5, 6, 7, 8, 10, 12.1, 16, 17, Patient Information
  • MedlinePlus Metformin
    Set id: n/a · Label effective or revised date: Last Revised - 10/15/2026 · Fetched at: 2026-11-02 · Sections used: all patient sections
  • openFDA drug label API (set_id search)
    Fetched at: 2026-11-02 · Sections used: openfda fields (application number, product type); pharm_class_epc absent
  • Drugs@FDA
    Fetched at: 2026-11-02 · Sections used: NOT FOUND (search page did not return results)

Information is taken from the cited sources and is for general reference only. It is not medical advice. Report side effects to FDA MedWatch at 1-800-FDA-1088. For a poison emergency call 1-800-222-1222. See prices for this drug