Background/Objectives <p>Obesity treatment can produce variable outcomes for different individuals. The aim of this analysis in adolescents with obesity was to investigate if baseline participant characteristics associated with BMI reduction from baseline to 56 weeks when treated with mid- or top-dose phentermine/topiramate (PHEN/TPM) compared to placebo.</p> Methods <p>A secondary analysis of a randomized, double-blind, placebo-controlled, clinical trial evaluating PHEN/TPM in adolescents with obesity was conducted. Participants, aged 12 to &lt;17 years with a BMI <Emphasis Type="Underline">≥</Emphasis>95th percentile, were randomly assigned in a 1:1:2 ratio to receive either placebo, mid-dose (PHEN/TPM 7.5 mg/46 mg) or top-dose (PHEN/TPM 15 mg/92 mg). Baseline characteristics included in the analysis were BMI, age, sex, race/ethnicity, pubertal status, diabetes status, depression status, cognitive function score, and quality of life score. The primary analysis used linear regression with BMI percent change from baseline to 56 weeks as the outcome with either mid- or top-dose PHEN/TPM compared to placebo.</p> Results <p>Two-hundred twenty-two participants were included in the final analysis. None of the baseline characteristics were statistically significantly associated with BMI reduction with mid- or top-dose PHEN/TPM compared to placebo.</p> Conclusions <p>Baseline characteristics were not predictive of BMI reduction with either dose of PHEN/TPM compared to placebo in adolescents with obesity.</p>