BackgroundMetformin (MET) therapy exerts positive effects improving glucose tolerance and preventing the evolution toward diabetes in insulin resistant patients. It has been shown that adding MET to exercise training does not improve insulin sensitivity. The aim of this study was to determine the effect of MET and exercise training alone or in combination on maximal aerobic capacity and, as a secondary end-point on quality of life indexes in individuals with insulin resistance.Methods75 insulin resistant patients were enrolled and subsequently assigned to MET (M), MET with exercise training (MEx), and exercise training alone (Ex). 12-weeks of supervised exercise-training program was carried out in both Ex and MEx groups. Cardiopulmonary exercise test and SF-36 to evaluate Health-Related Quality of Life (HRQoL) was performed at basal and after 12-weeks of treatment.ResultsCardiopulmonary exercise test showed a significant increase of peak VO2 in Ex and MEx whereas M showed no improvement of peak VO2 (∆ VO2 [CI 95%] Ex +0.26 [0.47 to 0.05] l/min; ∆ VO2 MEx +0.19 [0.33 to 0.05] l/min; ∆ VO2 M -0.09 [-0.03 to -0.15] l/min; M vs E p < 0.01; M vs MEx p < 0.01; MEx vs Ex p = ns). SF-36 highlighted a significant increase in general QoL index in the MEx (58.3 ± 19 vs 77.3 ± 16; p < 0.01) and Ex (62.1 ± 17 vs 73.7 ± 12; p < 0.005) groups.ConclusionsWe evidenced that cardiopulmonary negative effects showed by MET therapy may be counterbalanced with the combination of exercise training. Given that exercise training associated with MET produced similar effects to exercise training alone in terms of maximal aerobic capacity and HRQoL, programmed exercise training remains the first choice therapy in insulin resistant patients.