The pharmacokinetics of metformin and concentrations of haemoglobin A1C and lactate in Indigenous and non‐Indigenous Australians with type 2 diabetes mellitus

• Published in: British journal of clinical pharmacology Vol. 79; no. 4; pp. 617 - 623
• Main Authors: Duong, Janna K., Kumar, Shaun S., Furlong, Timothy J., Kirkpatrick, Carl M., Graham, Garry G., Greenfield, Jerry R., Williams, Ken M., Day, Richard O.
• Format: Journal Article
• Language: English
• Published: England Blackwell Science Inc 01.04.2015
• Subjects: Aboriginal and Torres Strait Islander patients; Aged; Australia; Creatinine - blood; Cross-Sectional Studies; Diabetes Mellitus, Type 2 - blood; Diabetes Mellitus, Type 2 - drug therapy; Glycated Hemoglobin A - analysis; Humans; Hypoglycemic Agents - blood; Hypoglycemic Agents - pharmacokinetics; Hypoglycemic Agents - therapeutic use; kidney disease; Lactic Acid - blood; Metabolic Clearance Rate; metformin; Metformin - blood; Metformin - pharmacokinetics; Metformin - therapeutic use; Middle Aged; Oceanic Ancestry Group; Pharmacokinetics; Population Groups; type 2 diabetes mellitus; pharmacokinetics; type 2 diabetes mellitus; kidney disease; metformin; Aboriginal and Torres Strait Islander patients
• ISSN: 0306-5251; 1365-2125
• DOI: 10.1111/bcp.12525

Aims To compare the pharmacokinetics of metformin between diabetic Indigenous (Aboriginal and Torres Strait Islander) and non‐Indigenous patients. Methods An observational, cross‐sectional study was conducted on type 2 diabetic Indigenous and non‐Indigenous patients treated with metformin. Blood samples were collected to determine metformin, lactate, creatinine and vitamin B12 concentrations and glycosylated haemoglobin levels. A population model was used to determine the pharmacokinetic parameters. Results The Indigenous patients (median age 55 years) were younger than the non‐Indigenous patients (65 years), with a difference of 10 years (95% confidence interval 6–14 years, P < 0.001). The median glycosylated haemoglobin was higher in the Indigenous patients (8.5%) than in the non‐Indigenous patients (7.2%), with a difference of 1.4% (0.8–2.2%, P < 0.001). Indigenous patients had a higher creatinine clearance (4.3 l h−1) than the non‐Indigenous patients (4.0 l h−1), with a median difference of 0.3 l h−1 (0.07–1.17 l h−1; P < 0.05). The ratio of the apparent clearance of metformin to the creatinine clearance in Indigenous patients (13.1, 10.2–15.2; median, interquartile range) was comparable to that in non‐Indigenous patients (12.6, 9.9–14.9). Median lactate concentrations were also similar [1.55 (1.20–1.88) vs. 1.60 (1.35–2.10) mmol l−1] for Indigenous and non‐Indigenous patients, respectively. The median vitamin B12 was 306 pmol l−1 (range 105–920 pmol l−1) for the Indigenous patients. Conclusions There were no significant differences in the pharmacokinetics of metformin or plasma concentrations of lactate between Indigenous and non‐Indigenous patients with type 2 diabetes mellitus. Further studies are required in Indigenous patients with creatinine clearance <30 ml min−1.