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

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Abstract

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.

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