{
 "query": "metformin",
 "ingredient": "metformin",
 "slug": "metformin",
 "rxcui": "6809",
 "brands": [
  "Glumetza",
  "Glucophage",
  "Riomet"
 ],
 "names": [
  "metformin",
  "metformin hydrochloride"
 ],
 "classes": [
  {
   "id": "A10BA",
   "name": "Biguanides"
  }
 ],
 "alternatives": [
  "phenformin"
 ],
 "label": {
  "route_mode": "ORAL",
  "route_counts": {
   "ORAL": 353
  },
  "boxed_warning": "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 Warnings and Precautions (5.1) ] . Steps to reduce the risk of and manage metformin-associated lactic acidosis in these high risk groups are pr...",
  "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. Metformin hydrochloride tablets is a 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)",
  "contraindications": "Metformin hydrochloride tablets are contraindicated in patients with: Severe renal impairment (eGFR below 30 mL/min/1.73 m 2 ) [see Warnings and Precautions (5.1) ]. Hypersensitivity to metformin. Acute or chronic metabolic acidosis, including diabetic ketoacidosis, with or without coma. Severe renal impairment (eGFR below 30 mL/min/1.73 m 2 ) (4 , 5.1) Hypersensitivity to metformin (4) Acute or chronic metabolic acidosis, including diabetic ketoacidosis, with or without coma. (4)",
  "warnings_and_cautions": "Lactic Acidosis: See boxed warning. (5.1) Vitamin B 12 Deficiency: Metformin may lower vitamin B 12 levels. Measure hematological parameters annually and vitamin B 12 at 2 to 3 year intervals and manage any abnormalities. (5.2) Hypoglycemia with Concomitant Use with Insulin and Insulin Secretagogues: Increased risk of hypoglycemia when used in combination with insulin and/or an insulin secretagogue. Lower dose of insulin or insulin secretagogue may be required (5.3) 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, 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 inc...",
  "warnings": "",
  "adverse_reactions": "The following adverse reactions are also discussed elsewhere in the labeling: Lactic Acidosis [see Boxed Warning and Warnings and Precautions (5.1) ] Vitamin B 12 Deficiency [see Warnings and Precautions (5.2) ] Hypoglycemia [see Warnings and Precautions (5.3) ] For metformin hydrochloride tablets, the most common adverse reactions (>5.0%) are diarrhea, nausea/vomiting, flatulence, asthenia, indigestion, abdominal discomfort, and headache. (6.1) To report SUSPECTED ADVERSE REACTIONS, contact Aurobindo Pharma USA, Inc. at 1-866-850-2876 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch . 6.1 Clinical Studies Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. In a U.S. clinical trial of metformin hydrochloride in patients with type 2 diabetes mellitus, a total of 141 patients received metformin hydrochloride up to 2550 mg per day. Adverse reactions reported in greater than 5% of metformin hydrochloride treated patients and that were more common than in placebo-trea...",
  "drug_abuse_and_dependence": "",
  "controlled_substance": "",
  "recent_major_changes": "Boxed Warning 04/2026",
  "information_for_patients": "Advise the patient to read the FDA-approved patient labeling (Patient Information). Lactic Acidosis: Explain the risks of lactic acidosis, its symptoms, and conditions that predispose to its development. Advise patients to discontinue metformin hydrochloride tablets immediately and to promptly notify their healthcare provider if unexplained hyperventilation, myalgias, malaise, unusual somnolence or other nonspecific symptoms occur. Counsel patients against excessive alcohol intake and inform patients about importance of regular testing of renal function while receiving metformin hydrochloride tablets. Instruct patients to inform their doctor that they are taking metformin hydrochloride tablets prior to any surgical or radiological procedure, as temporary discontinuation may be required [see Warnings and Precautions (5.1) ]. Hypoglycemia Inform patients that hypoglycemia may occur when metformin hydrochloride tablets are coadministered with oral sulfonylureas and insulin. Explain to patients receiving concomitant therapy the risks of hypoglycemia, its symptoms and treatment, and conditions that predispose to its development [see Warnings and Precautions (5.3) ]. Vitamin B 12 Deficie...",
  "spl_medguide": "",
  "clinical_studies": "14.1 Metformin Hydrochloride Adult Clinical Studies A double-blind, placebo-controlled, multicenter US clinical trial involving obese patients with type 2 diabetes mellitus whose hyperglycemia was not adequately controlled with dietary management alone (baseline fasting plasma glucose [FPG] of approximately 240 mg/dL) was conducted. Patients were treated with metformin hydrochloride (up to 2550 mg/day) or placebo for 29 weeks. The results are presented in Table 7. Table 7: Mean Change in Fasting Plasma Glucose and HbA1c at Week 29 Comparing Metformin Hydrochloride vs Placebo in Patients with Type 2 Diabetes Mellitus Metformin Hydrochloride (n=141) Placebo (n=145) p-Value FPG (mg/dL) Baseline Change at FINAL VISIT 241.5 \u201353.0 237.7 6.3 NS* 0.001 Hemoglobin A 1c (%) Baseline Change at FINAL VISIT 8.4 \u20131.4 8.2 0.4 NS* 0.001 * Not statistically significant Mean baseline body weight was 201 lbs and 206 lbs in the metformin hydrochloride and placebo arms, respectively. Mean change in body weight from baseline to week 29 was -1.4 lbs and -2.4 lbs in the metformin hydrochloride and placebo arms, respectively. A 29-week, double-blind, placebo-controlled study of metformin hydrochloride and ...",
  "brand_name": "Metformin Hydrochloride",
  "manufacturer": "REMEDYREPACK INC.",
  "application_number": "ANDA077095",
  "pharm_class_epc": [],
  "route": [
   "ORAL"
  ],
  "effective_time": "20260821",
  "set_id": "073cf6d9-7142-4d8b-898e-174c62a1f76f",
  "has_boxed_warning": true,
  "controlled": false,
  "mentions_rems": false
 },
 "faers": {
  "total": 360100,
  "serious": 252500,
  "death": 30495,
  "hospitalization": 132114,
  "primary_suspect": 358413,
  "top_reactions": [
   [
    "Diarrhoea",
    23750
   ],
   [
    "Nausea",
    22390
   ],
   [
    "Acute Kidney Injury",
    19838
   ],
   [
    "Drug Ineffective",
    18650
   ],
   [
    "Fatigue",
    18395
   ],
   [
    "Lactic Acidosis",
    17903
   ],
   [
    "Blood Glucose Increased",
    17478
   ],
   [
    "Vomiting",
    15456
   ],
   [
    "Off Label Use",
    14825
   ],
   [
    "Dyspnoea",
    13780
   ],
   [
    "Headache",
    12445
   ],
   [
    "Dizziness",
    12370
   ],
   [
    "Pain",
    11831
   ],
   [
    "Weight Decreased",
    11809
   ],
   [
    "Asthenia",
    11031
   ]
  ],
  "by_year": {
   "2019": 36965,
   "2020": 34532,
   "2021": 28347,
   "2022": 26107,
   "2023": 26058,
   "2024": 24980,
   "2025": 25346,
   "2026": 12315
  },
  "by_year_primary": {
   "2019": 36929,
   "2020": 34489,
   "2021": 28243,
   "2022": 25801,
   "2023": 25760,
   "2024": 24688,
   "2025": 24980,
   "2026": 12102
  }
 },
 "faers_base": {
  "total": 20692304,
  "serious_share": 0.5742697381596559,
  "death_share": 0.09102355155810585
 },
 "recalls": [
  {
   "class": "Class II",
   "date": "20250225",
   "reason": "Presence of Foreign Tablets/Capsules.",
   "firm": "A-S Medication Solutions LLC",
   "status": "Ongoing"
  },
  {
   "class": "Class II",
   "date": "20211227",
   "reason": "CGMP Deviations- Detection of N-Nitrosodimethylamine (NDMA) levels in excess of the Acceptable Daily Intake Limit.",
   "firm": "VIONA PHARMACEUTICALS INC",
   "status": "Terminated"
  },
  {
   "class": "Class II",
   "date": "20210601",
   "reason": "CGMP Deviations: Detection of N-Nitrosodimethylamine (NDMA) levels in excess of the Acceptable Daily Intake Limit.",
   "firm": "VIONA PHARMACEUTICALS INC",
   "status": "Terminated"
  },
  {
   "class": "Class II",
   "date": "20210504",
   "reason": "Presence of foreign substance: identified as activated carbon.",
   "firm": "SUN PHARMACEUTICAL INDUSTRIES INC",
   "status": "Terminated"
  },
  {
   "class": "Class III",
   "date": "20210325",
   "reason": "Failed Moisture Limits: Out of specification for water content",
   "firm": "SUN PHARMACEUTICAL INDUSTRIES INC",
   "status": "Terminated"
  },
  {
   "class": "Class II",
   "date": "20201012",
   "reason": "CGMP Deviations: detection of N-Nitrosodimethylamine (NDMA) impurity above the acceptable intake level (per manufacturer)",
   "firm": "Direct Rx",
   "status": "Terminated"
  },
  {
   "class": "Class II",
   "date": "20201006",
   "reason": "CGMP Deviations: detection of N-Nitrosodimethylamine (NDMA) impurity above the acceptable intake level (per manufacturer)",
   "firm": "PD-Rx Pharmaceuticals, Inc.",
   "status": "Terminated"
  },
  {
   "class": "Class II",
   "date": "20201006",
   "reason": "CGMP Deviations: detection of N-Nitrosodimethylamine (NDMA) impurity above the acceptable intake level (per manufacturer)",
   "firm": "PD-Rx Pharmaceuticals, Inc.",
   "status": "Terminated"
  },
  {
   "class": "Class II",
   "date": "20201002",
   "reason": "CGMP Deviations: detection of N-Nitrosodimethylamine (NDMA) impurity above the acceptable intake level",
   "firm": "Marksans Pharma Limited",
   "status": "Terminated"
  },
  {
   "class": "Class II",
   "date": "20201002",
   "reason": "CGMP Deviations: detection of N-Nitrosodimethylamine (NDMA) impurity above the acceptable intake level",
   "firm": "Marksans Pharma Limited",
   "status": "Terminated"
  },
  {
   "class": "Class II",
   "date": "20200819",
   "reason": "CGMP Deviations",
   "firm": "BAYSHORE PHARMACEUTICALS",
   "status": "Terminated"
  },
  {
   "class": "Class II",
   "date": "20200819",
   "reason": "CGMP Deviations",
   "firm": "BAYSHORE PHARMACEUTICALS",
   "status": "Terminated"
  }
 ],
 "recall_total": 22,
 "drugsfda": {
  "applications": 101,
  "nda": 6,
  "anda": 94,
  "first_approval": "19950303",
  "rems": false,
  "rems_last": "",
  "labeling_supplements": 40,
  "labeling_recent": 3,
  "sponsors": [
   "AARXION ANDA HLDING",
   "ACTAVIS ELIZABETH",
   "ACTAVIS LABS FL INC",
   "ADAPTIS",
   "AJANTA PHARMA LTD",
   "ALIGNSCIENCE PHARMA",
   "ALKEM",
   "ALKEM LABS LTD"
  ],
  "unapproved": false,
  "first_approval_fmt": "03/03/1995"
 },
 "trials": {
  "total": 3134,
  "completed": 2039,
  "terminated": 298,
  "with_results": 781,
  "industry": 1494,
  "phase3": 755,
  "results_share": 0.3830308974987739,
  "terminated_share": 0.09508615188257817
 },
 "pubmed": {
  "rct": 2144,
  "meta": 721,
  "recent_rct": 469,
  "cochrane": [
   {
    "pmid": "42573030",
    "title": "Glucagon-like peptide-1 receptor agonist-based regimens compared with metformin-based regimens for preventing cardiovascular disease in adults with type 2 diabetes mellitus",
    "year": "2026"
   },
   {
    "pmid": "42333644",
    "title": "Preconception and first-trimester metformin for improving pregnancy outcomes in women with polycystic ovary syndrome",
    "year": "2026"
   },
   {
    "pmid": "41631535",
    "title": "Metformin for asthma exacerbations",
    "year": "2026"
   },
   {
    "pmid": "38837240",
    "title": "Metformin for preventing the progression of chronic kidney disease",
    "year": "2024"
   },
   {
    "pmid": "38695827",
    "title": "Metformin for endometrial hyperplasia",
    "year": "2024"
   },
   {
    "pmid": "33347618",
    "title": "Metformin treatment before and during IVF or ICSI in women with polycystic ovary syndrome",
    "year": "2020"
   },
   {
    "pmid": "32794179",
    "title": "Metformin versus the combined oral contraceptive pill for hirsutism, acne, and menstrual pattern in polycystic ovary syndrome",
    "year": "2020"
   },
   {
    "pmid": "32501595",
    "title": "Metformin monotherapy for adults with type 2 diabetes mellitus",
    "year": "2020"
   },
   {
    "pmid": "31845767",
    "title": "Metformin for ovulation induction (excluding gonadotrophins) in women with polycystic ovary syndrome",
    "year": "2019"
   },
   {
    "pmid": "31794067",
    "title": "Metformin for prevention or delay of type 2 diabetes mellitus and its associated complications in persons at increased risk for the development of type 2 diabetes mellitus",
    "year": "2019"
   },
   {
    "pmid": "30998259",
    "title": "Metformin and second- or third-generation sulphonylurea combination therapy for adults with type 2 diabetes mellitus",
    "year": "2019"
   },
   {
    "pmid": "30039871",
    "title": "Metformin for women who are overweight or obese during pregnancy for improving maternal and infant outcomes",
    "year": "2018"
   }
  ]
 },
 "payments": {
  "year": "2024",
  "usd": 0.0,
  "records": 0,
  "by_name": [],
  "names_checked": [
   "metformin",
   "Glumetza",
   "Glucophage",
   "Riomet"
  ],
  "source": "bulk-index"
 },
 "partd": {
  "year": "2024",
  "claims": 34375334,
  "beneficiaries": 8812400,
  "spend": 408558855.68,
  "by_brand": [
   {
    "brand": "Metformin HCl",
    "claims": 23961097,
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    "is_generic": true
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   {
    "brand": "Metformin HCl ER",
    "claims": 10256666,
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   },
   {
    "brand": "Metformin ER Gastric",
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   },
   {
    "brand": "Metformin ER Osmotic",
    "claims": 71458,
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   },
   {
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    "claims": 3112,
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   }
  ],
  "per_claim": 11.885233047626533
 },
 "mdl": [],
 "dsc": [
  {
   "date": "20160408",
   "title": "FDA revises warnings regarding use of the diabetes medicine metformin in certain patients with reduced kidney function",
   "url": "https://www.fda.gov/Drugs/DrugSafety/ucm493244.htm",
   "kind": "drug",
   "matched": "metformin"
  }
 ],
 "settlements": [],
 "prescrire": null,
 "eml": {
  "listed": true,
  "status": "AddedToEml",
  "name": "metformin",
  "matched": "metformin",
  "stewardship": []
 },
 "exposure": {
  "years": [
   "2024",
   "2025",
   "2026"
  ],
  "reports_recent": 61770,
  "fills": 34375334,
  "per_million": 1796.9279949396273,
  "ratio": 0.6489565195178411,
  "median": 2768.949753790441
 },
 "scores": {
  "safety": {
   "score": 62,
   "letter": "D",
   "why": [
    "Carries an FDA boxed warning, the strongest warning the FDA issues (-30)",
    "FDA issued 1 Drug Safety Communication(s) naming this drug since 2010, most recently 2016 (-8)",
    "1,797 FDA reports naming it as the suspect drug per million Medicare fills, 0.6x the median drug on this site",
    "Death share in reports is near or below the FAERS average (0.9x)"
   ],
   "weight": 0.35
  },
  "evidence": {
   "score": 92,
   "letter": "A",
   "why": [
    "2144 randomized trials and 721 systematic reviews/meta-analyses indexed in PubMed",
    "On the WHO Model List of Essential Medicines (shown for context; no score effect)",
    "12 independent Cochrane review(s) exist",
    "Only 38% of completed registered trials posted results (-8)"
   ],
   "weight": 0.25
  },
  "regulatory": {
   "score": 84,
   "letter": "B",
   "why": [
    "Recalls since 2016: 0 Class I, 19 Class II, 2 Class III across 94 generic makers (-7)",
    "3 label changes approved since 2021 (-4)",
    "Label lists recent major changes to warnings or indications (-5)"
   ],
   "weight": 0.15
  },
  "conflict": {
   "score": 100,
   "letter": "A",
   "why": [
    "Pharma paid doctors $0 tied to this drug last year: negligible",
    "Not named in any pending federal MDL"
   ],
   "weight": 0.15
  },
  "options": {
   "score": 90,
   "letter": "A",
   "why": [
    "Generic versions approved (94 applications)",
    "1 same-class alternative(s) (-10)"
   ],
   "weight": 0.1
  }
 },
 "total": 81,
 "grade": "B",
 "questions": [
  "In 2016 the FDA issued a safety communication about this drug (FDA revises warnings regarding use of the diabetes medicine metformin in certain patients with reduced kidney ). Does that risk apply to me?",
  "This drug carries a boxed warning. Which specific risk does it cover, and does it apply to me?",
  "The most-reported problems in FDA's adverse event data are diarrhoea, nausea, acute kidney injury. How would we recognize and handle those?",
  "Why this one over phenformin? What would make you pick one of those instead?",
  "What result are we expecting, by when, and what is the plan if it does not happen?",
  "If 100 people like me took this drug, how many would actually get better because of it, and how many would be harmed by it? (Doctors call these the number needed to treat and the number needed to harm.)"
 ]
}