Examining the Pharmacokinetic-Pharmacodynamic Relationship of Metformin in Type 2 Diabetic Patients with Varying Renal Function in Abuja

Metformin remains the first-line oral hypoglycaemic agent for type 2 diabetes, but its accumulation risk in patients with reduced renal function requires careful pharmacokinetic-pharmacodynamic characterisation in Nigerian populations, where renal impairment is common and often undetected. This study examined the pharmacokinetic-pharmacodynamic relationship of metformin across different renal function categories in type 2 diabetic patients at a tertiary hospital in Abuja, Federal Capital Territory. A prospective cross-sectional pharmacokinetic study was conducted in 72 patients stratified by eGFR into categories: above 60, 45 to 60, 30 to 45, and below 30 mL/min/1.73m2. Metformin plasma concentrations were measured at peak and trough using validated HPLC methods. Pharmacodynamic endpoints included fasting plasma glucose, HbA1c, and lactate concentrations. Pharmacokinetic parameters were compared across renal function strata using ANOVA. Results showed progressive accumulation of metformin in patients with reduced renal function, with significantly elevated trough concentrations in the eGFR 30 to 45 category (p < 0.001). Lactate concentrations, while within reference ranges overall, were significantly higher in the lowest eGFR category (p < 0.01). HbA1c reduction was comparable across renal function groups at equivalent plasma concentrations. The study provides the first PK-PD analysis of metformin in a Nigerian tertiary hospital population, demonstrating clinically important concentration-renal function relationships that support current guidelines for dose review in patients with eGFR below 45. Keywords: metformin, pharmacokinetics, pharmacodynamics, renal function, type 2 diabetes