Evaluating potential predictors of weight loss response to liraglutide in adolescents with obesity: A post hoc analysis of the randomized, placebo-controlled SCALE Teens trial

Abstract

Background: As childhood obesity prevalence increases, determining which patients respond to anti-obesity medications would strengthen personalized approaches to obesity treatment. In the SCALE Teens trial among pubertal adolescents with obesity (NCT02918279), liraglutide 3.0 mg (or maximum tolerated dose) significantly reduced body mass index (BMI) standard deviation score on average versus placebo. That said, liraglutide effects on BMI reduction varied greatly among adolescents, similar to adults.

Objectives: To identify post hoc characteristics predictive of achieving ≥5% and ≥10% BMI reductions at 56 weeks with liraglutide versus placebo in adolescents from the SCALE Teens trial.

Methods: Logistic regression analysis was performed in 251 adolescents treated with liraglutide (n = 125) or placebo (n = 126) for 56 weeks. Baseline characteristics (selected a priori) included sex, race, ethnicity, age, Tanner (pubertal) stage, glycemic status (hyperglycemia [type 2 diabetes/prediabetes] vs. normoglycemia), obesity category (Class II/III vs. I), severity of depression symptoms (Patient Health Questionnaire-9), and weight variability (weight fluctuations over time). The effects of early responder status (≥4% BMI reduction at week 16) on week 56 response were assessed using descriptive statistics.

Results: Baseline characteristics did not affect achievement of ≥5% and ≥10% BMI reductions at week 56 in adolescents treated with liraglutide. Further, there was no association between weight variability and BMI reduction. Early liraglutide responders appeared to have greater BMI and body weight reductions at week 56 compared with early non-responders.

Conclusions: This secondary analysis suggests that adolescents with obesity may experience significant BMI reductions after 56 weeks of liraglutide treatment, regardless of their sex, race, ethnicity, age, pubertal stage, glycemic status, obesity category, severity of depression symptoms, or weight variability. Early response may predict greater week 56 response.

Keywords: anti-agents; glucagon-like peptide-1 receptor agonists; liraglutide; obesity; paediatric obesity; weight management.

FIGURE 1

Study design. The SCALE Teens trial included a 12-week lifestyle therapy-only run-in period, a 56-week treatment period (during which participants were randomized 1:1 to receive liraglutide or placebo, and which consisted of a 4-week dose escalation and 52-week maintenance phases), and a 26-week off-treatment lifestyle therapy-only follow-up period. Participants received lifestyle therapy throughout the entire trial. MTD, maximum tolerated dose; s.c., subcutaneous; SCALE, Satiety and Clinical Adipose Liraglutide Evidence. ^aDose escalation could be prolonged up to 8 weeks if required.

FIGURE 2

Subgroup analyses for reduction of BMI of (A) ≥5% and (B) ≥10% from baseline to week 56 for participants randomized to liraglutide versus placebo. Error bars are 95% CI. BMI, body mass index; CDC, Centers for Disease Control and Prevention; CI, confidence interval; NA, not available; OR, odds ratio; PHQ-9, Patient Health Questionnaire-9 score. ^aThe p value for treatment difference by subgroup interaction unless stated otherwise. ^bThe p value for treatment difference. ^cPrediabetes (fasting plasma glucose 100 to ≤125 mg/dL [5.6 to ≤6.9 mmol/L] or a glycated haemoglobin level 5.7% to ≤6.4%) or type 2 diabetes (fasting plasma glucose ≥126 mg/dL [≥7.0 mmol/L] and/or a glycated haemoglobin level ≥6.5%). ^dClass II/III (severe) obesity (BMI ≥120% of the 95th percentile and/or absolute BMI ≥35 kg/m², whichever was lower) or Class I obesity (≥95th percentile to <120% of the 95th percentile or absolute BMI <35 kg/m²) defined by CDC age- and sex-specific growth charts. ^eParticipants with PHQ-9 score ≥15 (indicating symptoms of severe depression) at screening were excluded from the trial. ^fAnalyses for race were not performed for a ≥10% reduction in BMI. In the model for which the predictor was race, no participants in the placebo group achieved this outcome between baseline and week 56; therefore, analyses could not be completed.

FIGURE 3

Change in (A) BMI and (B) body weight from baseline to week 56 by early responder status. Data are observed means for participants included in the early responder analysis (i.e., those with baseline and week 16 BMI [Figure 3A] or body weight [Figure 3B] assessments). Each data point is the mean change in BMI (Figure 3A) or body weight (Figure 3B) for all participants with available data at the timepoint. Early responders were participants who achieved ≥4% BMI reduction at week 16 (Figure 3A) or who achieved ≥4% weight loss at week 16 (Figure 3B); early non-responders were participants who did not achieve ≥4% BMI reduction or ≥4% weight loss at week 16. The pie charts present the proportions of participants assessed for early responder status (n = 119 for liraglutide, n = 123 for placebo) at baseline who were either early responders or early non-responders, as defined by change in BMI (Figure 3A) or body weight (Figure 3B) in each treatment group. BMI, body mass index.