Metformin Side Effects: Common, Serious & FDA Warnings
Based on 433,000+ FDA adverse event reports, the most-reported metformin reactions include nausea, diarrhoea, and blood glucose increased. FDA reports 6 active Class II recalls of metformin, primarily for failed dissolution specifications. The FDA-approved label carries a boxed warning.
WARNING: LACTIC ACIDOSIS WARNING: LACTIC ACIDOSIS See full prescribing information for complete boxed warning . Postmarketing cases of metformin-associated lactic acidosis have resulted in death, hypothermia, hypotension, and resistant bradyarrhythmias. Symptoms included malaise, myalgias, respiratory distress, somnolence, and abdominal pain. Laboratory abnormalities included elevated blood lactate levels, anion gap acidosis, increased lactate/pyruvate ratio, and metformin plasma levels generally >5 mcg/mL. ( 5.1 ) Risk factors include renal impairment, concomitant use of certain drugs, age ≥65 years old, radiological studies with contrast, surgery and other procedures, hypoxic states, excessive alcohol intake, and hepatic impairment. Steps to reduce the risk of and manage metformin-associated lactic acidosis in these high-risk groups are provided in the Full Prescribing Information. ( 5.1 ) If lactic acidosis is suspected, discontinue ZITUVIMET and institute general supportive measures in a hospital setting. Prompt hemodialysis is recommended. ( 5.1 ) 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, and hepatic impairment. Steps to reduce the risk of and manage metformin-associated lactic acidosis in these high risk groups are provided in the full prescribing information [see Dosage and Administration ( 2.2 )>, Contraindications ( 4 ), Warnings and Precautions ( 5.1 ), Drug Interactions ( 7 ), and Use in Specific Populations ( 8.6 , 8.7 )] . If metformin-associated lactic acidosis is suspected, immediately discontinue ZITUVIMET and institute general supportive measures in a hospital setting. Prompt hemodialysis is recommended [see Warnings and Precautions ( 5.1 )] .
Common Side Effects of Metformin
The most-reported reactions in the FDA Adverse Event Reporting System (FAERS) for metformin. Percentages reflect the share of reports mentioning each reaction; a single report may include multiple reactions. Reports indicate co-occurrence, not causation.
| Reaction | Reports | % of total |
|---|---|---|
| Nausea | 29,724 | 6.9% |
| Diarrhoea | 27,711 | 6.4% |
| Blood Glucose Increased | 27,482 | 6.3% |
| Fatigue | 21,186 | 4.9% |
| Vomiting | 19,221 | 4.4% |
| Lactic Acidosis | 18,813 | 4.3% |
| Acute Kidney Injury | 17,807 | 4.1% |
| Weight Decreased | 17,360 | 4.0% |
| Dyspnoea | 16,468 | 3.8% |
| Dizziness | 15,629 | 3.6% |
Serious Outcomes and FDA Warnings
FAERS reports flagged with a serious outcome (death, hospitalization, life-threatening, disability, or congenital anomaly), plus reactions surfaced in the FDA-approved label's Warnings section. Reports indicate co-occurrence, not causation.
| Outcome flag | Reports |
|---|---|
| Serious reports (any flag) | 289,272 |
| Hospitalization | 150,872 |
From the FDA-approved label, Section 5.1: Lactic Acidosis
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, hypothermia, hypotension and resistant bradyarrhythmias have occurred with severe acidosis. Metformin-associated lactic acidosis was characterized by elevated blood lactate concentrations (>5 mmol/Liter), anion gap acidosis (without evidence of ketonuria or ketonemia), and an increased lactate/pyruvate ratio; metformin plasma levels were generally >5 mcg/mL.Show full Section 5.1
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 ZITUVIMET. In ZITUVIMET treated patients with a diagnosis or strong suspicion of lactic acidosis, prompt hemodialysis is recommended to correct the acidosis and remove accumulated metformin (metformin HCl 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 ZITUVIMET and report these symptoms to their health care 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 ( 2.2 ) and Clinical Pharmacology ( 12.3 )]: Before initiating ZITUVIMET, obtain an estimated glomerular filtration rate (eGFR). ZITUVIMET is contraindicated in patients with an eGFR below 30 mL/min/1.73 m 2 [see Contraindications ( 4 )]. ZITUVIMET is not recommended in patients with an eGFR between 30 and less than 45 mL/min/1.73 m 2 because these patients require a lower dosage of sitagliptin than what is available in the fixed combination ZITUVIMET product. Obtain an eGFR at least annually in all patients taking ZITUVIMET. In patients at increased risk for the development of renal impairment (e.g., the elderly), renal function should be assessed more frequently. Drug Interactions The concomitant use of ZITUVIMET 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 [see Drug Interactions ( 7 )]. Therefore, 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 [see Use in Specific Populations ( 8.5 )]. Radiological 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 ZITUVIMET at the time of, or prior to, an iodinated contrast imaging procedure in patients with an eGFR between 30 and 60 mL/min/1.73 m 2 ; 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 ZITUVIMET 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. ZITUVIMET 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 also cause prerenal azotemia. When such events occur, discontinue ZITUVIMET. Excessive Alcohol Intake Alcohol potentiates the effect of metformin on lactate metabolism and this may increase the risk of metformin-associated lactic acidosis. Warn patients against excessive alcohol intake while receiving ZITUVIMET. Hepatic Impairment Patients with hepatic impairment have developed with cases of metformin-associated lactic acidosis. This may be due to impaired lactate clearance resulting in higher lactate blood levels. Therefore, avoid use of ZITUVIMET in patients with clinical or laboratory evidence of hepatic disease.
From the FDA-approved label, Section 5.4: Acute Renal Failure
There have been postmarketing reports of worsening renal function, including acute renal failure, sometimes requiring dialysis. Before initiation of therapy with ZITUVIMET and at least annually thereafter, renal function should be assessed. In patients in whom development of renal dysfunction is anticipated, particularly in elderly patients, renal function should be assessed more frequently and ZITUVIMET discontinued if evidence of renal impairment is present. ZITUVIMET is contraindicated in patients with severe renal impairment [see Contraindications ( 4 ) and Warnings and Precautions ( 5.1 )].
Metformin Recalls
FDA enforcement actions matched to metformin via openFDA's structured generic_name field and the NDC bridge. Ongoing recalls are listed below (verify on FDA →); closed recalls are grouped in the disclosure that follows.
| Date | Reason | Class | Quantity | Status |
|---|---|---|---|---|
| 2025-04-16 | CGMP Deviations Glenmark Pharmaceuticals Inc., USA | Class II | N/A | Ongoing |
| 2025-04-02 | Presence of Foreign Tablets/Capsules. A-S Medication Solutions LLC | Class II | 411 180-count bottles | Ongoing |
| 2020-07-01 | CGMP Deviations: FDA analysis detected N-Nitrosodimethylamine (NDMA) impurity above the acceptable intake level Amneal Pharmaceuticals of New York, LLC | Class II | N/A | Ongoing |
Show 17 closed recalls (2020 to 2022)
Includes resolved and terminated recalls matched to metformin. Most recent first.
| Date | Reason | Class | Quantity | Status |
|---|---|---|---|---|
| 2022-02-02 | CGMP Deviations- Detection of N-Nitrosodimethylamine (NDMA) levels in excess of the Acceptable Daily Intake Limit. VIONA PHARMACEUTICALS INC | Class II | 23,8416/100 count bottles | Terminated |
| 2021-06-30 | CGMP Deviations: Detection of N-Nitrosodimethylamine (NDMA) levels in excess of the Acceptable Daily Intake Limit. VIONA PHARMACEUTICALS INC | Class II | 21240 bottles | Terminated |
| 2021-05-19 | Presence of foreign substance: identified as activated carbon. SUN PHARMACEUTICAL INDUSTRIES INC | Class II | 50868 bottles | Terminated |
| 2021-04-21 | Microbial Contamination of Non-Sterile Product SUN PHARMACEUTICAL INDUSTRIES INC | Class II | 13,834 bottles | Terminated |
| 2021-04-14 | Failed Moisture Limits: Out of specification for water content SUN PHARMACEUTICAL INDUSTRIES INC | Class III | 2520 bottles | Terminated |
| 2020-11-11 | CGMP Deviations: detection of N-Nitrosodimethylamine (NDMA) impurity above the acceptable intake level (per manufacturer) PD-Rx Pharmaceuticals, Inc. | Class II | 125 bottles | Terminated |
| 2020-11-11 | CGMP Deviations: detection of N-Nitrosodimethylamine (NDMA) impurity above the acceptable intake level Marksans Pharma Limited | Class II | a) 64,590 b) 23,834 c) 109,125 d) 27839 bottles | Terminated |
| 2020-11-11 | CGMP Deviations: detection of N-Nitrosodimethylamine (NDMA) impurity above the acceptable intake level (per manufacturer) Direct Rx | Class II | 88 bottles | Terminated |
| 2020-11-11 | CGMP Deviations: detection of N-Nitrosodimethylamine (NDMA) impurity above the acceptable intake level (per manufacturer) PD-Rx Pharmaceuticals, Inc. | Class II | 1683 bottles | Terminated |
| 2020-11-11 | CGMP Deviations: detection of N-Nitrosodimethylamine (NDMA) impurity above the acceptable intake level Marksans Pharma Limited | Class II | 368,976 bottles | Terminated |
| 2020-09-02 | CGMP Deviations BAYSHORE PHARMACEUTICALS | Class II | 594 bottles | Terminated |
| 2020-09-02 | CGMP Deviations BAYSHORE PHARMACEUTICALS | Class II | 3984 bottles | Terminated |
| 2020-07-22 | CGMP Deviations: FDA analysis detected N-Nitrosodimethylamine (NDMA) impurity above the acceptable intake level Lupin Pharmaceuticals Inc. | Class II | 59,568 bottles | Terminated |
| 2020-07-22 | CGMP Deviations: FDA analysis detected N-Nitrosodimethylamine (NDMA) impurity above the acceptable intake level Lupin Pharmaceuticals Inc. | Class II | 95,886 bottles | Terminated |
| 2020-07-22 | CGMP Deviations: FDA analysis detected N-Nitrosodimethylamine (NDMA) impurity above the acceptable intake level Lupin Pharmaceuticals Inc. | Class II | 64,344 bottles | Terminated |
| 2020-07-22 | CGMP Deviations: FDA analysis detected N-Nitrosodimethylamine (NDMA) impurity above the acceptable intake level Lupin Pharmaceuticals Inc. | Class II | 273,060 bottles | Terminated |
| 2020-07-01 | CGMP Deviations: FDA analysis detected N-Nitrosodimethylamine (NDMA) impurity above the acceptable intake level Marksans Pharma Limited | Class II | 11279 bottles | Terminated |
Metformin Shortages
FDA-listed shortages of metformin products. Strength and dosage-form level detail.
Is Metformin Safe?
Metformin is FDA-approved. The label's Warnings and Precautions section covers lactic acidosis (Section 5.1), pancreatitis (Section 5.2), heart (Section 5.3), acute renal failure (Section 5.4), vitamin b12 (Section 5.5), hypoglycemia with concomitant use with insulin or insulin secretagogues (Section 5.6), hypersensitivity reactions (Section 5.7), severe and disabling arthralgia (Section 5.8), bullous pemphigoid (Section 5.9).
As with any prescription, the assessment of safety is individual; consult a clinician about your own risk profile.
FDA-Approved Indications
Metformin is FDA-approved for use in the condition categories below. The FDA-approved label’s Indications and Usage section is shown verbatim.
ZITUVIMET is a combination of sitagliptin, a dipeptidyl peptidase-4 (DPP-4) inhibitor, and metformin hydrochloride (HCl), a biguanide, indicated as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus. ( 1 ) Limitations of Use: ZITUVIMET is not recommended in patients with type 1 diabetes mellitus. ( 1 ) ZITUVIMET has not been studied in patients with a history of pancreatitis. ( 1 ) ZITUVIMET is indicated as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus.Show full Indications and Usage
Limitations of Use ZITUVIMET is not recommended in patients with type 1 diabetes mellitus. ZITUVIMET has not been studied in patients with a history of pancreatitis. It is unknown whether patients with a history of pancreatitis are at increased risk for the development of pancreatitis while using ZITUVIMET. [see Warnings and Precautions ( 5.2 )].
Frequently Asked Questions
What are the most-reported side effects of metformin?
Is metformin the same as Riomet?
Has metformin been recalled?
What are metformin's current ongoing recalls about?
What do FDA recall classes mean?
Does metformin have an FDA boxed warning?
Data Sources & Methodology
How each section of this page is sourced, and how often the data is refreshed.
| Source | Endpoint | Refresh |
|---|---|---|
| FAERS reactions | openFDA /drug/event.json count API. Aggregated per drug per reaction term; we do not store individual reports. | Daily |
| Recalls | openFDA /drug/enforcement.json. Drugs matched via three confidence-tracked strategies: structured generic name (HIGH), NDC code bridge (MEDIUM), text token parse (LOW). Only HIGH and MEDIUM matches surface here. | 6 hours |
| Shortages | FDA Drug Shortages list. | Daily |
| Boxed warnings & label sections | openFDA /drug/label.json. Labels are stable; monthly cadence is sufficient. | Monthly |
| Condition categories | Synonym-mapped from drug_labels.indications. Methodology at /methodology/. | Per-drug |
What we do not do. We do not invent, paraphrase, or extrapolate drug claims. Every figure on this page comes from a query against an openFDA endpoint. If the data is unavailable, the section gracefully omits rather than filling the space with editorial guesswork.