Body Composition and Lifestyle Interventions in Pharmacological Treatment of Acquired Hypothalamic Obesity: A Systematic Review of Randomized Controlled Trials

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ABSTRACT Objective This review aimed to systematically evaluate the effects of pharmacological interventions on body composition outcomes and lifestyle intervention as background therapy in patients with acquired hypothalamic obesity (aHO). Methods Searches were conducted in PubMed, Embase, the Cochrane Library, CINAHL, and CNKI for studies published between July 24, 2015, and November 8, 2025. Eligible studies were full‐text randomized controlled trials (RCTs) evaluating pharmacological and/or lifestyle weight management interventions in patients with aHO of any age. Outcomes included four domains: anthropometric and body composition measures, metabolic markers, behavioral and energy‐related outcomes, and adverse events. Risk of bias was assessed using the adapted Cochrane Risk of Bias Tool, and certainty of evidence was evaluated using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) framework. Owing to substantial heterogeneity in interventions and outcome measurements, only descriptive synthesis was performed. Results Seven RCTs were included. Semaglutide demonstrated sustained weight loss, while long‐acting exenatide reduced fat mass without substantial lean mass loss. Tesomet was associated with reductions in both body weight and lean mass, whereas diazoxide showed limited efficacy for weight management. Several interventions improved satiety and reduced hunger, although metabolic findings were inconsistent across studies. Adverse events were mostly mild to moderate. Risk of bias assessment identified one study at high risk of bias and one with some concerns. According to the GRADE framework, certainty of evidence was low for anthropometric/body composition, metabolic, and behavioral/energy outcomes and moderate for adverse events. Conclusions Current evidence suggests that selected pharmacological interventions may improve weight‐related and body composition outcomes in aHO; however, evidence remains limited and of predominantly low certainty. Existing studies are constrained by inadequate assessment of lean body mass and poorly standardized lifestyle interventions. Future large‐scale, long‐term RCTs incorporating systematic body composition assessment and structured lifestyle intervention protocols are needed.