Why do you hold metformin (biguanide oral hypoglycemic agent) in a hospitalized patient with impaired renal function or at risk of lactic acidosis?

Why Metformin is Held in Hospitalized Patients

Metformin must be discontinued immediately upon hospitalization because acute illness creates multiple conditions that dramatically increase the risk of life-threatening lactic acidosis—including impaired renal function, tissue hypoxia, hemodynamic instability, and reduced lactate clearance. 1, 2

Primary Mechanism of Risk

Metformin decreases hepatic uptake of lactate, causing lactate accumulation in the bloodstream. 2 When combined with the metabolic stress of acute hospitalization, this creates a dangerous cycle where:

• Metformin accumulates because it is renally eliminated and hospitalized patients frequently develop acute kidney injury or have pre-existing renal impairment 2
• Lactate production increases from tissue hypoxia, sepsis, hypoperfusion, or other acute conditions 3, 2
• Lactate clearance decreases due to liver dysfunction, renal impairment, or hemodynamic compromise 3, 2

Specific High-Risk Conditions in Hospitalized Patients

Acute conditions requiring immediate metformin discontinuation include: 1, 4, 2

• Sepsis or systemic infection with hemodynamic instability - causes tissue hypoxia and impairs lactate clearance 3, 2
• Acute kidney injury or worsening renal function - metformin accumulates when eGFR drops, particularly dangerous below 45 mL/min/1.73 m² 2
• Acute congestive heart failure - especially with hypoperfusion or hypoxemia, creates tissue hypoxia 5, 2
• Cardiovascular collapse, shock, or acute myocardial infarction - causes prerenal azotemia and tissue hypoxia 2
• Dehydration or volume depletion - from NPO status, surgical procedures, or restricted fluid intake 2
• Hepatic dysfunction - impairs lactate clearance since the liver is the primary site of lactate removal 2
• Hypoxic states - from respiratory failure, pulmonary disease decompensation, or any condition causing tissue hypoxemia 2

Evidence Supporting Discontinuation

The FDA label explicitly states that metformin should be discontinued when acute conditions occur that may predispose to lactic acidosis. 2 The American Diabetes Association specifically recommends that "metformin should be avoided in unstable or hospitalized patients with heart failure" and discontinued in patients with "sepsis or systemic infection with hemodynamic instability, acute kidney injury, or anticipated renal impairment." 5, 1

Critical warning signs of metformin-associated lactic acidosis (MALA) include: 4, 2

• Malaise, myalgias, abdominal pain
• Respiratory distress, increased somnolence
• Hypotension and resistant bradyarrhythmias
• Laboratory findings: lactate >5 mmol/L, anion gap acidosis, lactate:pyruvate ratio increased, metformin levels >5 mcg/mL

The Mortality Risk

Metformin-associated lactic acidosis carries approximately 50% mortality when it occurs. 6 While the overall incidence is low in stable outpatients (2-9 per 100,000 patient-years), the risk increases dramatically during acute hospitalization when multiple precipitating factors converge. 3, 6 Almost 97% of reported MALA cases presented with independent risk factors for lactic acidosis, supporting that metformin plays a contributory role in an already vulnerable patient. 7

Appropriate Inpatient Management

Insulin is the preferred and safest treatment for hyperglycemia in hospitalized patients: 5, 1

• Basal-bolus insulin regimen for patients who are eating regularly 5
• Basal insulin with correctional doses for patients with poor oral intake, starting at reduced doses of 0.1-0.15 units/kg/day 5
• Avoid premixed insulin formulations in hospitalized elderly patients due to threefold higher hypoglycemia risk 5

Common Pitfalls to Avoid

Do not continue metformin simply because renal function appears stable on admission - acute deterioration is unpredictable and the consequences are severe. 1, 2 The American Diabetes Association guidelines explicitly state metformin "should be avoided in unstable or hospitalized patients." 5, 1

Do not restart metformin at discharge without reassessing renal function and confirming resolution of acute conditions. 1 Metformin should only be restarted when kidney function has been reassessed, acute illness has resolved, and the patient is hemodynamically stable with normal oral intake. 1

Contrast to Recent Observational Data

One recent 2025 observational study 8 suggested potential benefits of continuing metformin during hospitalization, showing reduced hypoglycemia and mortality. However, this contradicts established FDA labeling 2, American Diabetes Association guidelines 5, 1, and the fundamental pharmacology of metformin in acute illness. The observational study likely suffered from selection bias—sicker patients with contraindications were appropriately not given metformin, making the metformin group appear healthier. Given the 50% mortality of MALA and explicit guideline recommendations, the conservative approach of discontinuation remains the standard of care.