Outcomes of Phentermine-Topiramate in Children Living with Duchenne Muscular Dystrophy

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.

Individuals with a genetic diagnosis of DMD, who were prescribed PHEN/TPM from January 1, 2015, to April 25, 2025, were identified from the electronic medical record system of Children's Hospital Colorado (CHCO). A final cohort of six individuals treated for at least 6 months had clinic-obtained weights documented and were included in the analysis.

All patients were aged 9.9-16.9 years, with baseline weight 45-108.2 kg and BMI 29.5-39.7 kg/m2. Treatment duration ranged from 0.6 to 4.2 years. In the first year of therapy, median BMI decreased by 3.75 kg/m2 (interquartile ranges [IQRs]: -5.5 to -2.6), BMI standard deviation (SD) by 0.57 (IQR: -0.99 to -0.31), and weight SD by 0.73 (IQR: -1.17 to -0.59). Over the full treatment course (0.6-4.2 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 nonlinear 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.

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.