1682-P: Weight Endpoints in Randomized Controlled Trials (Rcts) of Adults Eligible for Antiobesity Medications (AOM)—A Systematic Literature Review (SLR)

Introduction & Objective: Obesity affects 40% of American adults; 75% of whom have multiple obesity related comorbidities (ORC). Here we synthesize data on body weight (BW) and waist circumference (WC) from trials of adults eligible for AOM (BMI ≥30kg/m2 or ≥27kg/m2 with ≥1 ORC).

Methods: An PRISMA-guided SLR was performed to identify published manuscripts (2018-23) and conference abstracts (2021-23) of RCTs in adults eligible for AOM. Mean (95% confidence interval [CI ]) treatment differences were reported for continuous variables and odds ratios (OR; 95%CI) for categorical variables. Change in % BW and WC (cm) was summarized at ≤12 weeks, ≤26 weeks, and ≥27 weeks. ORs for achieving ≥15% BW loss were also summarized.

Results: From 1935 records, 39 eligible studies reported on BW and 20 on WC. Relative to placebo, % BW loss ranged from -1.1 (-1.2, 1.0; dapagliflozin [DAPA] 10 mg) to -4.4 (-4.5, -4.3; exenatide 10 μg) ≤12 weeks; -1.5 (-1.6, -1.4) (DAPA 10 mg) to -8.9 (-10.0, -7.8; semaglutide [SGL] 2.4 mg) ≤weeks; and -0.5 (-0.6, -0.4; DAPA 10 mg) by 156 weeks to -17.8 (-19.3, -16.3; tirzepatide [TZ] 15 mg) by 72 weeks. Compared to placebo, OR (95% CI) for achieving ≥15% BW loss ranged from 2.2 (0.9, 5.5; liraglutide [LIR] 3.0 mg) to 24.7 (17.9, 34.1; TZ 15 mg). Relative to placebo, change in WC ranged from -0.2 (-1.1, 0.7; DAPA 10 mg) to -3.1 (-4.2, -2.0; SGL 2.4 mg) ≤12 weeks, -1.7 (-2.7, -0.7; DAPA 10 mg) to -4.4 (-5.4, -3.4; SGL 2.4 mg) ≤26 weeks, and -2.7 (-3.5, -1.9); LIR 3.0 mg) by 56 weeks to -14.5 (-15.9, -13.0; TZ 15 mg) by 72 weeks. Two studies compared interventions head-to-head.

Conclusions: Emerging pharmacotherapies are showing longer term and greater weight loss. While data on WC was less frequently reported, it can provide important insights on the risk of developing ORC. Between-study heterogeneity in design and populations was high; and future studies to explore the importance of these factors will help better inform quantitative evidence syntheses.