IntroductionIn patients affected by insulin resistance (IR), metformin (MET) therapy has been shown to exert its positive effects by improving glucose tolerance and preventing the evolution to diabetes. Recently, it was shown that the addition of metformin to physical training did not improve sensitivity to insulin or peak oxygen consumption (peak VO2). The purpose of this study was to establish the effect of metformin and exercise, separately or in combination, on systolic left ventricular (LV) function in individuals with IR.MethodsSeventy-five patients with IR were enrolled and subsequently assigned to MET, combination MET and exercise, or exercise alone. The LV systolic and diastolic functions were evaluated with standard echocardiography tissue Doppler imaging (TDI) and speckle tracking echocardiography at baseline and after 12 weeks of treatment.ResultsMET, administered alone or in association with exercise, improved longitudinal LV function, as evidenced by an increase in systolic (S) wave on TDI, alongside increases in longitudinal global strain and strain rate in comparison to the group undergoing physical training alone. The traditional echocardiographic parameters showed no statistically significant differences among the three groups before or after the different cycles of therapy.ConclusionsTreatment with MET, either with or without exercise, but not exercise alone, produced a significant increase in global longitudinal LV systolic function at rest. These findings validate the observation that the use of MET alone or in association with exercise has a crucial role to counteract the negative effects of IR on cardiovascular function.Electronic supplementary materialThe online version of this article (doi:10.1007/s40119-016-0057-3) contains supplementary material, which is available to authorized users.