PEI-LIN LEELai, Shang-RuShang-RuLaiChien, Meng-YuehMeng-YuehChienGooley, Joshua JJoshua JGooleyFeng, Hsin-ChunHsin-ChunFengLin, Ming-TzerMing-TzerLinChiu, Hung-ChihHung-ChihChiuSHIH-KUO CHENLiu, Po-KangPo-KangLiuYUNG-HSUAN CHENKu, Bo-WenBo-WenKuWang, Su-MeiSu-MeiWangChang, Chin-HaoChin-HaoChangWEI-SHIUNG YANGCHONG-JEN YU2026-02-052026-02-052026https://www.scopus.com/record/display.uri?eid=2-s2.0-105027272547&origin=resultslisthttps://scholars.lib.ntu.edu.tw/handle/123456789/735768Study Objectives Weight gain after continuous positive airway pressure (CPAP) initiation in obstructive sleep apnea (OSA) is common, but its mechanism and relevance remain unclear. This open-label randomized trial evaluated CPAP effects on energy expenditure, intake, body composition, physical activity, and appetite-regulatory hormones. Methods Patients with OSA were randomized (1:1) to 12-week CPAP or inactive control. The primary outcome was resting energy expenditure (REE). Secondary outcomes included dietary intake, eating behavior, fat mass (FM), fat-free mass (FFM), and activity count. Tertiary outcomes included appetite-regulatory hormones. CPAP effects were assessed as baseline-adjusted between-group differences using intention-to-treat (ITT) analysis; Per-protocol analysis (completers) served as sensitivity analysis. Results Of 52 randomized participants, 45 completed the study. In ITT analysis, CPAP had no effect on REE (8.6 kcal/day [95% CI = −51.5 to 68.7]; p = .774) or caloric intake (144.4 kcal/day [95% CI = −123.1 to 411.9]; p = .283). Although insignificant in morning, CPAP significantly increased evening body weight (p = .017) and body mass index in morning and evening (p = .040 and .030). CPAP also increased FFM, raised acylated ghrelin and insulin-like growth factor 1, and reduced cortisol and cognitive restraint. No changes were observed in macronutrient intake, FM, activity, insulin resistance, leptin, or neuropeptide Y. Per-protocol findings were similar. Conclusions CPAP-induced weight gain, probably primarily from FFM, occurred without measurable changes in REE, activity, or significant increases in caloric intake. Accompanying hormonal and behavioral changes suggest a subtle positive energy balance. This gain may not reflect adverse metabolic effects and supports evaluating CPAP’s metabolic impact through body composition, not weight alone. Clinical trial registration Registry: ClinicalTrials.gov; Name: Validation of Sleep Healthcare System; URL: https://clinicaltrials.gov/study/NCT04252482; Identifier: NCT04252482. Statement of Significance The physiological basis and clinical relevance of weight gain following CPAP therapy remain insufficiently defined. This study found that CPAP-induced weight gain was probably primarily due to increases in FFM, without measurable changes in REE, physical activity, or significant increases in reported caloric intake. Given the potential underestimation in dietary reporting, the observed gain—together with hormonal and behavioral changes—suggests a subtle positive energy balance. These findings indicate that post-CPAP weight gain may not reflect adverse metabolic effects and highlight the value of assessing body composition, rather than weight alone, in clinical follow-up.enbasal metabolismbody weightenergy intakeenergy metabolisminsulin resistancejournal article10.1093/sleep/zsaf259