Metformin Half-Life
The plasma elimination half-life of metformin is approximately 6.2 hours in patients with normal renal function, while the blood elimination half-life is approximately 17.6 hours. 1
Pharmacokinetic Parameters in Normal Renal Function
- Following oral administration in adults with type 2 diabetes and normal renal function, metformin has a plasma elimination half-life of approximately 6.2 hours 1
- The blood elimination half-life is significantly longer at approximately 17.6 hours, suggesting that erythrocyte mass serves as a compartment of distribution 1
- Research studies confirm a mean elimination half-life during multiple dosing of approximately 5 hours in patients with good renal function 2
- Steady-state plasma concentrations are reached within 24 to 48 hours of initiating therapy 1
Renal Clearance and Elimination
- Approximately 90% of absorbed metformin is eliminated via the renal route within the first 24 hours 1
- Metformin is excreted unchanged in urine without undergoing hepatic metabolism—no metabolites have been identified in humans 1
- Renal clearance is approximately 3.5 times greater than creatinine clearance, indicating that tubular secretion is the major route of elimination 1
- The population mean renal clearance in healthy subjects and diabetic patients with good renal function is 510 ± 130 mL/min 2
Impact of Renal Impairment on Half-Life
- In patients with decreased renal function, both the plasma and blood half-life of metformin are prolonged and renal clearance is decreased 1
- The terminal half-life measured from urinary excretion can extend to approximately 16 hours when measured up to 60 hours post-dose 3
- Renal clearance and total oral clearance decrease approximately in proportion to creatinine clearance 2
- This prolonged half-life in renal impairment increases the risk of drug accumulation and lactic acidosis, which is why metformin must be discontinued when eGFR falls below 30 mL/min/1.73 m² 4, 5
Clinical Implications of Half-Life
- The relatively short plasma half-life of 6.2 hours supports twice-daily dosing for immediate-release formulations 1
- Extended-release formulations allow once-daily dosing by achieving maximum plasma concentrations more slowly while providing similar total exposure 6
- The discrepancy between plasma (6.2 hours) and blood (17.6 hours) half-lives suggests potential for gradual accumulation in peripheral tissues, which has implications for the rare but serious complication of lactic acidosis 3
- Despite the short plasma half-life, the longer blood half-life means that metformin effects persist beyond what plasma measurements alone would suggest 1