A randomised controlled trial to investigate the efficacy of dexamphetamine compared to placebo for treating obesity complicated by obstructive sleep apnoea

Abstract

Background: Obesity is a major global health concern associated with significant morbidity, including cardiovascular disease, type 2 diabetes, and obstructive sleep apnoea (OSA). Although effective pharmacotherapies exist, high costs limit accessibility. Dexamphetamine (DEX), a centrally acting stimulant with anorexigenic and psychotropic properties, may represent a cost-effective alternative, though its use in obesity is restricted.

Objective: To evaluate the safety and efficacy of DEX for weight loss in adults with obesity and OSA, and its effects on cardiovascular and behavioural outcomes.

Methods: In this double-blind, randomised, placebo-controlled trial, 62 adults (BMI 25–70 kg/m², AHI >15 events/hour) were assigned 1:1 to DEX (up to 60 mg/day) or placebo for six months, followed by two-year observation. Outcomes included anthropometry, OSA severity, cardiovascular safety, executive function, and eating behaviours. Assessments included polysomnography, echocardiography, ECG, cognitive testing, and behavioural questionnaires.

Results: At six months, weight loss was significantly greater with DEX than placebo (16.6 kg vs. 3.7 kg; p < 0.001), with 75% achieving >10% weight loss. Significant reductions in BMI and waist circumference were observed. OSA severity improved with DEX, including reductions in AHI and oxygen desaturation, while controls worsened or showed minimal change. Cardiovascular parameters remained stable, with only a modest increase in heart rate and no serious adverse events. DEX was well tolerated, with low discontinuation rates and mild adverse effects. Eating behaviours improved, with no significant change in executive function.

Conclusion: DEX effectively promoted weight loss and improved OSA with good tolerability and no significant cardiovascular risk, supporting its potential as a cost-effective obesity treatment.