Durability of Semaglutide Effects After Treatment Discontinuation in HIV-Associated Lipohypertrophy: A Randomized, Double-Blind, Placebo-Controlled Phase 2b Clinical Trial.
4 affiliations
- 1Medical University of South Carolina, Department of Medicine and Pediatrics, Division of Infectious Disease, Charleston, South Carolina, USA.
- 2Case Western Reserve University, Department of Population and Quantitative Health Sciences, Cleveland, Ohio, USA.
- 3University Hospitals Cleveland Medical Center, Department of Medicine, Division of Infectious Disease, Cleveland, Ohio, USA.
- 4Saint Ignatius High School, Cleveland, Ohio, USA.
Abstract
Background
Human immunodeficiency virus (HIV)-associated lipohypertrophy is characterized by excess central and visceral adiposity and is associated with increased cardiometabolic risk among people with HIV (PWH). In a previously reported randomized trial, semaglutide significantly reduced body weight, regional adiposity, and insulin resistance over 32 weeks of active treatment. However, the durability of these benefits after treatment discontinuation is unknown.Methods
We conducted a randomized, placebo-controlled trial in PWH with HIV-associated lipohypertrophy. Participants were randomized to semaglutide or placebo for 32 weeks, followed by discontinuation of study drug and observational follow-up through week 56. The current analysis investigated effects of semaglutide at week 56, as compared to baseline and week 32. Outcomes included adipose tissue quantity by body compartment. Analyses were performed using intention-to-treat principles. This trial was registered at ClinicalTrials.gov (NCT04019197) and is complete.Results
Of 108 participants initially randomized, 92 completed the 32-week intervention and 80 participants (39 semaglutide, 41 placebo) completed the posttreatment phase. Participants previously assigned to semaglutide experienced increases in body weight, body mass index (BMI), waist circumference, total body fat, and visceral adipose tissue between weeks 32 and 56, accompanied by worsening glycemic indices and insulin resistance. Despite this rebound, net reductions in body weight, BMI, and waist circumference were retained at week 56 compared with baseline. Placebo-treated participants demonstrated relative stability across outcomes.Conclusions
Discontinuation of semaglutide in PWH with lipohypertrophy resulted in partial loss of improvements in weight, adiposity, and metabolic parameters. These findings support that sustained pharmacologic exposure is likely needed to achieve long-term benefit.
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BibTeX
@article{adekunle2026durability,
title = {{Durability of Semaglutide Effects After Treatment Discontinuation in HIV-Associated Lipohypertrophy: A Randomized, Double-Blind, Placebo-Controlled Phase 2b Clinical Trial.}},
author = {Ruth O Adekunle and Qian Wu and Abdus Sattar and Kianoush Ansari-Gilani and Danielle Labbato and Aaron A Fletcher and Aidan D McComsey and Allison Ross Eckard},
journal = {Open forum infectious diseases},
year = {2026},
month = oct,
doi = {10.1093/ofid/ofag631},
url = {https://europepmc.org/article/MED/42921178},
note = {CC BY},
}
RIS
TY - JOUR
TI - Durability of Semaglutide Effects After Treatment Discontinuation in HIV-Associated Lipohypertrophy: A Randomized, Double-Blind, Placebo-Controlled Phase 2b Clinical Trial.
AU - Ruth O Adekunle
AU - Qian Wu
AU - Abdus Sattar
AU - Kianoush Ansari-Gilani
AU - Danielle Labbato
AU - Aaron A Fletcher
AU - Aidan D McComsey
AU - Allison Ross Eckard
PY - 2026
DA - 2026/10/05
JO - Open forum infectious diseases
DO - 10.1093/ofid/ofag631
UR - https://europepmc.org/article/MED/42921178
AB - Background Human immunodeficiency virus (HIV)-associated lipohypertrophy is characterized by excess central and visceral adiposity and is associated with increased cardiometabolic risk among people with HIV (PWH). In a previously reported randomized trial, semaglutide significantly reduced body weight, regional adiposity, and insulin resistance over 32 weeks of active treatment. However, the durability of these benefits after treatment discontinuation is unknown.Methods We conducted a randomized, placebo-controlled trial in PWH with HIV-associated lipohypertrophy. Participants were randomized to semaglutide or placebo for 32 weeks, followed by discontinuation of study drug and observational follow-up through week 56. The current analysis investigated effects of semaglutide at week 56, as compared to baseline and week 32. Outcomes included adipose tissue quantity by body compartment. Analyses were performed using intention-to-treat principles. This trial was registered at ClinicalTrials.gov (NCT04019197) and is complete.Results Of 108 participants initially randomized, 92 completed the 32-week intervention and 80 participants (39 semaglutide, 41 placebo) completed the posttreatment phase. Participants previously assigned to semaglutide experienced increases in body weight, body mass index (BMI), waist circumference, total body fat, and visceral adipose tissue between weeks 32 and 56, accompanied by worsening glycemic indices and insulin resistance. Despite this rebound, net reductions in body weight, BMI, and waist circumference were retained at week 56 compared with baseline. Placebo-treated participants demonstrated relative stability across outcomes.Conclusions Discontinuation of semaglutide in PWH with lipohypertrophy resulted in partial loss of improvements in weight, adiposity, and metabolic parameters. These findings support that sustained pharmacologic exposure is likely needed to achieve long-term benefit.
SN - 2328-8957
ER -