Last reviewed 2026-04-20 · How we verify

Glucophage (metformin)

Activates AMP-activated protein kinase (AMPK) to reduce hepatic glucose production and improve insulin sensitivity without causing hypoglycemia.

At a glance

Mechanism of action

Metformin is the first-line drug for type 2 diabetes worldwide and the most prescribed diabetes medication. Derived from the French lilac plant (Galega officinalis), it primarily reduces hepatic glucose output and modestly improves peripheral insulin sensitivity. Uniquely among glucose-lowering drugs, it does not cause hypoglycemia or weight gain. The UKPDS trial demonstrated it reduces cardiovascular mortality in overweight diabetic patients. It is being investigated for anti-aging and cancer prevention properties.

Approved indications

• Controlled ovarian stimulation
• Diabetes mellitus type 2
• Induction of ovulation in polycystic ovarian syndrome
• Treatment Refractory Type 2 Diabetes Mellitus

Boxed warnings

• 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

• Diarrhea
• Nausea/Vomiting
• Flatulence
• Asthenia
• Indigestion
• Abdominal Discomfort
• Headache
• Abnormal Stools
• Hypoglycemia
• Myalgia
• Lightheaded
• Dyspnea

Serious adverse events

• Lactic Acidosis
• Vitamin B12 Deficiency
• Hepatocellular Liver Injury
• Cholestatic Liver Injury
• Mixed Hepatocellular Liver Injury

Key clinical trials

• Interventions Against Insulin Resistance in Pulmonary Arterial Hypertension (Phase 2)
• Window of Opportunity for Durvalumab (MEDI4736) Plus Metformin Trial of in Squamous Cell Carcinoma of the Head and Neck (EARLY/Phase 1)
• Treatment of Wolfram Syndrome Type 2 With the Chelator Deferiprone, and Incretin Based Therapy (Phase 2)
• NCT00004992 (Phase 3)
• A Randomized, Double-Blind, Placebo-Controlled, Multicenter Clinical Trial to Evaluate the Efficacy and Safety of Metformin in Combination With Secukinumab for the Treatment of Moderate-to-Severe Plaq (Phase 4)
• The Effect of Semaglutide on Disordered Eating Behaviour in Type 2 Diabetic Patients (Phase 4)
• Vitamin B12 Supplementation in Diabetic Neuropathy :1-year Double Blind Randomized Placebo-Controlled Trial (NA)
• Cofrogliptin Once Every 2 Weeks as Add-on Therapy to Metformin and Dapagliflozin Versus Daily Linagliptin in Patients With Type 2 Diabetes: A Multicenter, Randomized, Open-Label, Active-Controlled, No (Phase 4)

Primary sources

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Competitive intelligence

For the full competitive landscape — auto-detected comparators, recent regulatory actions across the set, upcoming PDUFA, patent timeline, sponsor landscape:

• Glucophage CI brief — competitive landscape report
• Glucophage updates RSS · CI watch RSS
• Generic (originally Merck Serono/Lipha) portfolio CI