Abstract Background/Objectives: To assess the effectiveness of the SLIMMER combined dietary and physical activity lifestyle intervention on clinical and metabolic risk factors, dietary intake, physical activity, and quality of life after 12 months, and to investigate whether effects sustained six months after the active intervention period ended. Subjects/Methods: SLIMMER was a randomised controlled intervention, implemented in Dutch primary healthcare. In total, 316 subjects aged 40–70 years with increased risk of type 2 diabetes were randomly allocated to the intervention group (10-month dietary and physical activity programme) or the control group (usual healthcare). All subjects underwent an oral glucose tolerance test and physical examination, and filled in questionnaires. Identical examinations were performed at baseline and after 12 and 18 months. Primary outcome was fasting insulin. Results: The intervention group showed significantly greater improvements in anthropometry and glucose metabolism. After 12 and 18 months, differences between intervention and control group were -2.7 kg (95% confidence interval (CI): −3.7; −1.7) and −2.5 kg (95% CI: −3.6; −1.4) for weight, and −12.1 pmol l −1 (95% CI: −19.6; −4.6) and −8.0 pmol l −1 (95% CI: −14.7; −0.53) for fasting insulin. Furthermore, dietary intake, physical activity, and quality of life improved significantly more in the intervention group than in the control group. Conclusions: The Dutch SLIMMER lifestyle intervention is effective in the short and long term in improving clinical and metabolic risk factors, dietary intake, physical activity, and quality of life in subjects at high risk of diabetes.