To compare the effects of lifestyle modification programs that prescribe low-glycemic load (GL) vs. low-fat diets in a randomized trial.Seventy-nine obese adults with type 2 diabetes received low-fat or low-GL dietary instruction, delivered in 40-week lifestyle modification programs with identical goals for calorie intake and physical activity. Changes in weight, HbA(1c), and other metabolic parameters were compared at weeks 20 and 40.Weight loss did not differ between groups at week 20 (low-fat: -5.7±3.7%; low-GL: -6.7±4.4%, p=.26) or week 40 (low-fat: -4.5±7.5%; low-GL: -6.4±8.2%, p=.28). Adjusting for changes in antidiabetic medications, subjects on the low-GL diet had larger reductions in HbA(1c) than those on the low-fat diet at week 20 (low-fat: -0.3±0.6%; low-GL: -0.7±0.6%, p=.01), and week 40 (low-fat: -0.1±1.2%; low-GL: -0.8±1.3%; p=.01). Groups did not differ significantly on any other metabolic outcomes (p≥.06).Results suggest that targeting GL, rather than dietary fat, in a low-calorie diet can significantly enhance the effect of weight loss on HbA(1c) in patients with type 2 diabetes.