2068-P: Effect of Phentermine/Topiramate on Insulin Sensitivity and Beta-Cell Function in Adolescents with Youth-Onset Type 2 Diabetes and Obesity

Introduction and Objective: First-line treatment for youth-onset type 2 diabetes (Y-T2D) does not improve insulin sensitivity (IS) and β-cell function (BCF). This study aims to evaluate phentermine/topiramate (PHEN/TPM) versus placebo on IS and BCF for adolescents with Y-T2D. Methods: A 24-week trial in adolescents, 12-20 years, with Y-T2D was conducted. Participants were randomized 1:1 to placebo or PHEN/TPM, an oral obesity medication. PHEN/TPM was increased to 15 mg/92 mg after 8 weeks. Participants treated with metformin ± insulin prior to enrollment remained on these medications. A 2 hour, 75-gram OGTT was performed at baseline and 24 weeks with assessment of insulinogenic index (IGI; ΔInsulin30/Δglucose30), IS (1/fasting insulin), and BCF relative to IS (oral deposition index [oDI]). Linear regression estimated the treatment effect on IS and BCF adjusted for baseline values. Results: Thirteen participants (mean age: 15.5 ± 2.07 years, 38.5% female) were randomized. Baseline HbA1c was 8.1% ± 1.7 with 53.8% of participants on insulin therapy. The estimated treatment difference (ETD) in oDI, insulin sensitivity and IGI were not statistically significant (Table 1). Conclusion: PHEN/TPM was not associated with significant changes in IS or BCF in adolescents with T2D compared to placebo. A larger sample size may be needed for significant improvements to surface in IS and BCF consequent to adiposity reductions with PHEN/TPM. Disclosure M.O. Bensignor: Research Support; Current; Dexcom, Inc., Vivus Inc. R. Freese: None. A.S. Kelly: Advisory Panel; Current; Boehringer Ingelheim International GmbH, Eli Lilly and Company, Novo Nordisk. Research Support; Current; Vivus, Novo Nordisk. K. Rudser: None. S. Arslanian: None. Funding National Institutes of Health NIDDK K23DK129721