Skeletal effects of GLP-1 receptor agonist…

Results

Eight RCTs (n = 493) were included. Three trials were at low risk of bias (Eriksson 2019; Hygum 2020; Hansen 2024) and five raised some concerns, principally regarding the randomization process and selective reporting; no agent is supported by more than one trial at low risk of bias. (Cai 2021 contributes two treatment arms assessed separately, giving nine comparisons in the risk-of-bias assessment.) Evidence was unevenly distributed across agents: semaglutide and dulaglutide were each evaluated in one trial, liraglutide in two, and exenatide in five. Five of the eight trials enrolled adults with type 2 diabetes, including all four that randomized an insulin comparator arm; three enrolled adults without diabetes, of which one was defined by obesity alone. By study-level mean baseline BMI, five trials lay in the obese range ( ≥ 30 kg/m²) and three in the overweight range (25 to <30 kg/m²). The single semaglutide trial (Hansen 2024; n = 64; low risk of bias), which produced the largest weight loss of any trial (estimated treatment difference [ETD] -6.8 kg vs placebo), reported reduced lumbar spine BMD (ETD - 0.018 g/cm², p = 0.007), reduced whole-body BMD (mean difference [MD] -0.02 g/cm²; 95% CI - 0.03 to -0.01), and increased C-terminal telopeptide (CTX; MD 166.50 pg/mL; 95% CI 66.60 to 266.40). Liraglutide was evaluated at two doses with divergent results. At the weight-management dose of 3.0 mg daily, in the only trial conducted in adults with obesity and without diabetes (Jensen 2024; ETD - 6.7 kg vs placebo), lumbar spine BMD (MD - 0.019 g/cm²; 95% CI - 0.034 to -0.004) and total hip BMD (MD - 0.013 g/cm²; 95% CI - 0.024 to -0.002) were reduced. At the diabetes dose of 1.8 mg daily (Hygum 2020; -3.8 kg), no site changed materially (lumbar spine MD 0.00 g/cm²; 95% CI - 0.01 to 0.01). Exenatide trials were inconsistent, ranging from 0.03 g/cm² (95% CI 0.02 to 0.03) at the lumbar spine (Renyuan 2015) to -0.04 g/cm² (95% CI - 0.15 to 0.07; Akyay 2023). Certainty of evidence was very low for every agent.

Skeletal effects of GLP-1 receptor agonist therapy in adults with overweight or obesity: a systematic review

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