Metformin reduces C-reactive protein but not complement factor C3 in overweight patients with Type 2 diabetes mellitus.

Aims: To determine the influence of metformin treatment on plasma C-reactive protein (CRP) and complement factor C3.
Methods: A double-blind, placebo-controlled trial of metformin in patients with poorly controlled Type 2 diabetes mellitus and body mass index > 25 kg/m2. CRP and C3 were analysed in stored plasma samples by in-house ELISAs. Patients attended two baseline visits before randomization and subsequently attended at 3, 6, 12 and 24 weeks post randomization. All patients gave informed consent according to a protocol approved by the Leeds Teaching Hospitals Research Ethics Committee.
Results: Baseline CRP in the patients randomized to placebo [1.33 (0.79, 2.25) mg/l] and metformin [1.24 (0.89, 1.71) mg/l] were similar (P = 0.8). Baseline CRP correlated with baseline C3 (r = 0.366) and HbA1c (r = 0.327). The difference in ratios of CRP levels at each visit to baseline between placebo- (n = 16) and metformin-treated (n = 26) subjects was significantly different at the 12-week (P = 0.002) and 24-week (P = 0.03) visits. The difference in CRP ratios between the two treatment groups remained significant after accounting for glycaemic control at both visits (P = 0.001 and P = 0.003, respectively). Baseline C3 was correlated with CRP. Baseline C3 was lower in the placebo-treated group [0.97 (0.88, 1.05) mg/ml] compared with the metformin-treated group [1.09 (1.02, 1.17) mg/ml, P = 0.03]. There was no difference in the mean change in C3 at any visit from baseline between placebo- and metformin-treated groups.
Conclusion: Metformin may have a specific interaction with mechanisms involved in CRP synthesis or secretion, not directly related to improved insulin sensitivity and dampening of chronic inflammation.