Comparative effectiveness of GLP-1 receptor agonists, SGLT2 inhibitors, DPP-4 inhibitors, and sulfonylureas on weight change among people with HIV: a real-world longitudinal cohort study

Obesity is common among people with HIV (PWH), yet evidence on weight loss with newer antidiabetic medications in this population is limited. We compared bodyweight change associated with glucagon-like peptide-1 receptor agonists (GLP-1RA), sodium–glucose cotransporter-2 (SGLT2) inhibitors, dipeptidyl peptidase-4 (DPP-4) inhibitors, and sulfonylureas among PWH. We conducted an active-comparator new-user cohort study using data from 9 U.S. sites in the Centers for AIDS Research Network of Integrated Clinical Systems. PWH initiating GLP-1RA, SGLT2 inhibitors, DPP-4 inhibitors, or sulfonylureas between 2013 and 2023 were included. The primary outcome was percent bodyweight change at 1 year, assessed using covariate-adjusted linear mixed models under an on-treatment approach. Secondary outcomes included absolute weight change (kg) and time to ≥ 5% and ≥ 10% loss, evaluated using adjusted Cox models. Weight trajectories up to 3 years were also examined. Among 1,572 PWH, GLP-1RA use was associated with the greatest mean percent weight loss at 1 year (–4.44%; 95% CI − 5.51 to − 3.36), followed by SGLT2 inhibitors (–1.00%; 95% CI − 2.25 to 0.24). DPP-4 inhibitors and sulfonylureas showed minimal change. Compared with sulfonylureas, GLP-1RA and SGLT2 inhibitor use was associated with a higher likelihood of achieving ≥ 5% and ≥ 10% weight loss. GLP-1RA–associated weight loss was greater among PWH without diabetes and those with higher body mass index, with semaglutide being associated with the largest reductions. Weight loss with GLP-1RA was nonlinear, with greater early reductions. GLP-1RA were associated with the greatest weight loss among PWH, supporting their use in a population with high cardiometabolic risk.