Purpose We investigated the effects of the macronutrient composition of diets with differing satiety values on fasting appetite-related hormone concentrations after weight loss and examined whether the hormone secretion adapted to changes in body fat mass (FM) and fat-free mass (FFM) during the weight maintenance period (WM). Methods Eighty-two men and women with obesity underwent a 7-week very-low-energy diet (VLED) and were then randomised to a higher-satiety food (HSF) group or a lower-satiety food (LSF) group during 24-weeks of the WM. The groups consumed isoenergetic foods with different satiety ratings and macronutrient compositions. Results During the WM, the HSF group consumed more protein and dietary fibre and less fat than the LSF group, but the groups showed similar changes in body weight and fasting appetite-related hormones. In the whole study sample, VLED induced 12 kg (p < 0.001) weight loss. At the end of the WM, weight regain was 1.3 kg (p = 0.004), ghrelin concentration increased, whereas leptin, insulin, and glucose concentrations decreased compared to pre-VLED levels (p < 0.001 for all). Peptide YY did not differ from pre-VLED levels. Changes in ghrelin levels were inversely associated with changes in FFM during weeks 0–12 of the WM (p = 0.002), while changes in leptin and insulin levels were positively associated with changes in FM during weeks 0–12 (p = 0.015 and p = 0.038, respectively) and weeks 12–24 (p < 0.001 and p = 0.022) of the WM. Conclusions The macronutrient composition of an isoenergetic WM diet did not affect fasting appetite-related hormone concentrations. Leptin and insulin adjusted to the reduced FM, whereas ghrelin reflected FFM during the first months of the WM. Trial registration isrctn.com, ID 67529475.

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