The aim of this interim analysis of the Look AHEAD trial was to investigate the effects of lifestyle intervention on changes in weight, fitness, and cardiovascular disease (CVD) risk factors after 4 years on the program. This multicentre randomized clinical trial recruited individuals (59.5% female; mean age: 58.7 years) with type 2 diabetes. A total of 5,145 participants were randomized to either an intensive lifestyle intervention (ILI; n=2,570) group or to the control group of patients who were only provided with diabetes support and education (DSE; n=2,575). The ILI produced greater weight losses, increases in fitness, and greater improvements in all CVD risk factors, except LDL cholesterol levels, compared with the DSE group. The greatest positive impact of the intervention on several of the risk factors was observed after the first year. Although there was a gradual attenuation of the effects over time, several positive effects of ILI were maintained compared to DSE across all 4 years for systolic blood pressure and HbA1c and HDL cholesterol levels. This study showed that a lifestyle intervention can generate long-term weight loss and improvements in fitness and sustained beneficial effects on CVD risk factors. In his editorial comment, Deedwania PC qualified the findings of the Look AHEAD trial as very interesting considering the risk of severe hypoglycemic events observed in clinical trials with drug therapy. He underlined the relatively low risk of hypoglycemia with ILI and the significant improvement in HbA1c which was achieved with ILI. He also highlighted the impressive effect of ILI on blood pressure and on the lipid profile that was similar to results observed with pharmacological intervention.