Weight loss has been associated with adaptations in energy expenditure. Identifying factors that counteract these adaptations are important for long-term weight loss and weight maintenance. The aim of this study was to investigate whether increased protein/carbohydrate ratio would reduce adaptive thermogenesis (AT) and the expected positive energy balance (EB) during weight maintenance after weight loss in participants with prediabetes in the postobese state. In 38 participants, the effects of 2 diets differing in protein/carbohydrate ratio on energy expenditure and respiratory quotient (RQ) were assessed during 48-h respiration chamber measurements ∼34 mo after weight loss. Participants consumed a high-protein (HP) diet (n = 20; 13 women/7 men; age: 64.0 ± 6.2 y; BMI: 28.9 ± 4.0 kg/m ²) with 25:45:30% or a moderate-protein (MP) diet (n = 18; 9 women/9 men; age: 65.1 ± 5.8 y; BMI: 29.0 ± 3.8 kg/m ²) with 15:55:30% of energy from protein:carbohydrate:fat. Predicted resting energy expenditure (REEp) was calculated based on fat-free mass and fat mass. AT was assessed by subtracting measured resting energy expenditure (REE) from REEp. The main outcomes included differences in components of energy expenditure, substrate oxidation, and AT between groups. EB (MP = 0.2 ± 0.9 MJ/d; HP = −0.5 ± 0.9 MJ/d) and RQ (MP = 0.84 ± 0.02; HP = 0.82 ± 0.02) were reduced and REE (MP: 7.3 ± 0.2 MJ/d compared with HP: 7.8 ± 0.2 MJ/d) was increased in the HP group compared with the MP group (P < 0.05). REE was not different from REEp in the HP group, whereas REE was lower than REEp in the MP group (P < 0.05). Furthermore, EB was positively related to AT (r_s = 0.74; P < 0.001) and RQ (r_s = 0.47; P < 0.01) in the whole group of participants. In conclusion, an HP diet compared with an MP diet led to a negative EB and counteracted AT ∼34 mo after weight loss, in participants with prediabetes in the postobese state. These results indicate the relevance of compliance to an increased protein/carbohydrate ratio for long-term weight maintenance after weight loss. The trial was registered at clinicaltrials.gov as NCT01777893.

Importance: A major issue in the management of craniopharyngioma-related obesity (CRO) is the ineffectiveness of the current therapeutic approaches. Objective: To study the efficacy of glucagon-like peptide-1 analogs compared with placebo in adults with obesity CRO. Design: A double-blind multicenter superiority randomized clinical in trial in two parallel arms. Setting: Eleven French University Hospital Centers. Participants: Adults with CRO (body mass index > 30 kg/m²) without the sign of recurrence of craniopharyngioma in the past year. Interventions: Exenatide or placebo injected subcutaneously twice a day during 26 weeks. Main Outcomes and Measures: The primary outcome was the mean change in body weight at week 26 in the intention-to-treat population. Secondary outcomes were eating behavior, calories intake, energy expenditure, cardiovascular, metabolic risk factor, quality of life, and the tolerance profile. Results: At week 26, weight decreased from baseline by a mean of −3.8 (SD 4.3) kg for exenatide and −1.6 (3.8) kg for placebo. The adjusted mean treatment difference was −3.1 kg (95% confidence interval [CI] −7.0 to 0.7, P = 0.11). Results were compatible with a higher reduction of hunger score with exenatide compared with placebo (estimated treatment difference in change from baseline to week 26: −2.3, 95% CI −4.5 to −0.2), while all other outcomes did not significantly differ between groups. Adverse events were more common with exenatide versus placebo, and occurred in, respectively, 19 (95%) participants (108 events) and 14 (70%) participants (54 events). Conclusions and Relevance: Combined with intensive lifestyle interventions, a 26-week treatment with exenatide was not demonstrated superior to placebo to treat craniopharyngioma-related obesity.