The relationship between metformin therapy and the fasting plasma lactate in type 2 diabetes: The Fremantle Diabetes Study

Aims To determine (i) which factors, including metformin, are associated with the fasting plasma lactate concentration in type 2 diabetes, and (ii) whether plasma lactate is associated with haemodynamic and metabolic effects. Methods We measured fasting plasma lactate in 272 well-characterized diabetic patients from a community-based sample, 181 (67%) of whom were taking metformin with or without other therapies. Linear regression analysis was used to identify predictors, including metformin therapy, of the plasma lactate, and to investigate associations between plasma lactate and resting pulse rate and serum bicarbonate. Factor analysis assessed independent relationships between groups of cosegregating variables. Results Metformin-treated patients had higher plasma lactate concentrations than nonmetformin-treated subjects (geometric mean [s.d. range] 1.86 [1.34-2.59] vs 1.58 [1.09-2.30] mmol l(-1), respectively; P < 0.001). In a linear regression model, plasma glucose, BMI and metformin use (but not dose) were independently associated with plasma lactate (P less than or equal to 0.028); after adjustment for the former two variables, metformin-treated patients had a mean plasma lactate 0.16 mmol l(-1) greater than in subjects not taking the drug. Factor analysis revealed that plasma lactate, plasma glucose, BMI and pulse rate cosegregated but serum bicarbonate was not in this grouping. Conclusions The present results show that metformin therapy increases the fasting plasma lactate in ambulant patients with type 2 diabetes from a community-based cohort. From associations in the data we hypothesize that this increase reflects (i) increased sympathetic activity in patients with the metabolic syndrome (ii) increased substrate (glucose) availability and (iii) a direct metformin effect.