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 wi th the fasting plasma lactate concentration in type 2 diabetes, and (ii) wh ether plasma lactate is associated with haemodynamic and metabolic effects. Methods We measured fasting plasma lactate in 272 well-characterized diabet ic patients from a community-based sample, 181 (67%) of whom were taking me tformin with or without other therapies. Linear regression analysis was use d to identify predictors, including metformin therapy, of the plasma lactat e, and to investigate associations between plasma lactate and resting pulse rate and serum bicarbonate. Factor analysis assessed independent relations hips 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 linea r regression model, plasma glucose, BMI and metformin use (but not dose) we re independently associated with plasma lactate (P less than or equal to 0. 028); after adjustment for the former two variables, metformin-treated pati ents 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 gluc ose, BMI and pulse rate cosegregated but serum bicarbonate was not in this grouping. Conclusions The present results show that metformin therapy increases the f asting plasma lactate in ambulant patients with type 2 diabetes from a comm unity-based cohort. From associations in the data we hypothesize that this increase reflects (i) increased sympathetic activity in patients with the m etabolic syndrome (ii) increased substrate (glucose) availability and (iii) a direct metformin effect.