Metformin Warnings & Precaution

FDA Boxed Warning: Lactic Acidosis Risk

Metformin carries a black box warning for lactic acidosis, with an incidence of 3-10 cases per 100,000 patient-years. Key pathophysiological mechanisms include:

Impaired lactate clearance due to reduced hepatic metabolism
Increased lactate production from anaerobic glycolysis
Renal insufficiency impairing metformin elimination

High-Risk Populations

Risk Factor	Relative Risk Increase	Clinical Action
eGFR <30 mL/min	12-fold	Absolute contraindication
Congestive heart failure (NYHA III-IV)	5-fold	Alternative therapy recommended
Chronic alcoholism	4-fold	Strict alcohol avoidance

Renal Function Monitoring Protocol

Current ADA/EASD guidelines recommend the following monitoring schedule:

Baseline and Ongoing Assessment

All patients: Measure eGFR before initiation
eGFR ≥60: Annual monitoring
eGFR 45-59: Repeat every 6 months
eGFR 30-44: Quarterly monitoring

Dose Modification Guidelines

Renal Function	eGFR (mL/min/1.73m²)	Maximum Daily Dose
Normal	≥90	2000mg
Mild impairment	60-89	2000mg
Moderate impairment	30-59	1000mg

Special Clinical Scenarios

Iodinated Contrast Administration

Intravenous contrast may cause acute kidney injury, requiring:

Pre-procedure eGFR assessment
Metformin discontinuation 48 hours pre-contrast
Re-evaluation of renal function pre-restart

Perioperative Management

Discontinue 24 hours before elective surgery
Withhold until normal oral intake resumes post-op
Monitor for acidosis in emergency surgeries