Outcomes of phentermine-topiramate in children living with Duchenne muscular dystrophy

Introduction Duchenne muscular dystrophy (DMD) is a progressive neuromuscular disorder associated with obesity due to low energy expenditure and high-dose corticosteroid treatment. Obesity significantly impacts quality of life in individuals with DMD and is consistently identified as a top family concern. Despite FDA approval of weight-loss medications for adolescents, including phentermine/topiramate (PHEN/TPM), there is limited evidence for their use in children with DMD, particularly regarding potential cardiac complications in a population already at elevated risk. Case Presentation We report clinical outcomes of PHEN/TPM therapy in six boys with DMD (aged 9.9-16.9 years) and body mass index (BMI) ranging 29.5 to 39.7 kg/m2, treated at Children's Hospital Colorado from January 2015 to April 2025. In the first year of therapy, median BMI decreased by 3.75 kg/m² (IQR: -5.5 to -2.6), BMI standard deviation (SD) by 0.57 ((IQR: -0.99 to -0.31), and weight SD by 0.59 ((IQR: -1.17 to -0.59 ). Over the full treatment course (0.6 to 4.2 years), median annualized changes were BMI -1.73 kg/m² (IQR: -2.93 to 0.17), BMI SD -0.31 (IQR:-0.44 to -0.15), and weight SD -0.30 (IQR:-0.70 to -0.11). Longitudinal analysis revealed significant non-linear trends for BMI and BMI SD, with nadir effect by year two. Cardiac parameters showed initial transient heart rate increase (HR, median +13.5 bpm at 0.5 years) but no significant changes in longitudinal follow-up of HR, systolic blood pressure, diastolic blood pressure, or left ventricular ejection fraction. Two individuals developed kidney stones; other adverse events were mild to moderate. Conclusion Treatment with PHEN/TPM in a small group of children with DMD and obesity was associated with clinically relevant reductions in measures of obesity and was generally well-tolerated with no significant adverse cardiac effects observed during extended follow-up. These findings support the potential use of PHEN/TPM as a weight management option in carefully selected individuals with DMD, though larger prospective studies are warranted.