Clinical effectiveness and predictors of response to topiramate plus lifestyle modification in youth with obesity seen in a weight management clinical setting

Abstract

Introduction: Obesity affects approximately 20% of U.S. youth. Anti-obesity medications (AOMs) are promising lifestyle modification adjuncts for obesity treatment, and topiramate is commonly prescribed in pediatric weight management clinics. It is important to determine "real-world" effectiveness of AOMs and, given shifts towards personalized approaches, characteristics potentially predicting better or worse response. We therefore sought to describe clinical effectiveness from topiramate plus lifestyle modification, and to determine if baseline phenotypic characteristics are associated with better or worse response.

Methods: We performed a retrospective cohort study (2012-2020) among youth (<18 years old) followed in a U.S. academic-based weight management clinic. Baseline characteristics (i.e., body mass index (BMI), liver function tests, eating-related behaviors) and outcomes (%BMI of 95^th percentile (%BMIp95), BMI, percent %BMI change, weight) were determined through review of electronic health records and clinic intake survey data.

Results: Among 282 youth prescribed topiramate plus lifestyle modifications (mean baseline age 12.7 years, %BMIp95 144%), %BMIp95 and percent BMI change were statistically significantly reduced at each time point (1.5-, 3-, 6-, and 12-month %BMIp95 reductions: -2.2, -3.9, -6.6, and -9.3 percentage points, respectively; percent BMI reduction: -1.2%, -1.9%, -3.2%, and -3.4%, respectively; all p<0.01). Considering multiple comparisons, no baseline characteristics statistically significantly predicted response at any time point.

Conclusions: We found that topiramate plus lifestyle modification reduced %BMIp95 and BMI among youth in a weight management clinical setting, and that no baseline characteristics evaluated were associated with response. These results should be considered preliminary given the observational nature of this study, and prospective studies are needed to further characterize clinical effectiveness and identify and confirm potential predictors of response.

Keywords: anti-obesity agents; obesity; obesity management; pediatric obesity; topiramate.

Figure 1

Changes in body mass index (BMI) percent of 95th percentile, BMI, and weight over time among 282 youth prescribed topiramate plus lifestyle modification in a weight management clinic.

Figure 2

Predictors of 1.5-month change in %BMIp95. Caption: *Not statistically significant after Holm procedure for multiple comparisons (uncorrected p-values shown); ALT, alanine aminotransferase; AST, aspartate aminotransferase; Class 1 Obesity, body mass index percent of the 95th percentile: 100th–119th percentile; Class 2 Obesity, body mass index percent of the 95th percentile: 120th–139th percentile; Class 3 Obesity, body mass index percent of the 95th percentile: ≥140th percentile; EF, enjoyment of food; EOE, enjoyment of eating; FR, food responsiveness; GAD-7, Generalized Anxiety Disorder–7; PHQ-9, Patient Health Questionnaire–9; SR, satiety responsiveness.

Figure 3

Predictors of 3-month change in %BMIp95. Caption: *Not statistically significant after Holm procedure for multiple comparisons (uncorrected p-values shown); ALT, alanine aminotransferase; AST, aspartate aminotransferase; Class 1 Obesity, body mass index percent of the 95th percentile: 100th–119th percentile; Class 2 Obesity, body mass index percent of the 95th percentile: 120th–139th percentile; Class 3 Obesity, body mass index percent of the 95th percentile: ≥140th percentile; EF, enjoyment of food; EOE, enjoyment of eating; FR, food responsiveness; GAD-7, Generalized Anxiety Disorder–7; PHQ-9, Patient Health Questionnaire–9; SR, satiety responsiveness.

Figure 4

Predictors of 6-month change in %BMIp95. Caption: *Not statistically significant after Holm procedure for multiple comparisons (uncorrected p-values shown); ALT, alanine aminotransferase; AST, aspartate aminotransferase; Class 1 Obesity, body mass index percent of the 95th percentile: 100th–119th percentile; Class 2 Obesity, body mass index percent of the 95th percentile: 120th–139th percentile; Class 3 Obesity, body mass index percent of the 95th percentile: ≥140th percentile; EF, enjoyment of food; EOE, enjoyment of eating; FR, food responsiveness GAD-7, Generalized Anxiety Disorder–7; PHQ-9, Patient Health Questionnaire–9; SR, satiety responsiveness.

Figure 5

Predictors of 12-month change in %BMIp95. Caption: *Not statistically significant after Holm procedure for multiple comparisons (uncorrected p-values shown); ALT, alanine aminotransferase; AST, aspartate aminotransferase; Class 1 Obesity, body mass index percent of the 95th percentile: 100th–119th percentile; Class 2 Obesity, body mass index percent of the 95th percentile: 120th–139th percentile; Class 3 Obesity, body mass index percent of the 95th percentile: ≥140th percentile; EF, enjoyment of food; EOE, enjoyment of eating; FR, food responsiveness GAD-7, Generalized Anxiety Disorder–7; PHQ-9, Patient Health Questionnaire–9; SR, satiety responsiveness.