Durability of Semaglutide Effects After Treatment Discontinuation in HIV-Associated Lipohypertrophy: A Randomized, Double-Blind, Placebo-Controlled Phase 2b Clinical Trial
- Design
- Randomized trial · 108 participants · Intermediate outcome
- Match to healthy normal-weight adults aged 55–75
- Different populationINDIRECT: all participants had HIV-associated lipohypertrophy, excess central and visceral fat with raised cardiometabolic risk that the target group lacks; no BMI, age or diabetes data are reported.
- Could weight loss explain it?
- Not applicableNot applicable: the outcomes are weight, fat compartments and related measures after stopping the drug.
- Study tier
- Study tier 3Small randomized trial (108 randomized, 80 completing follow-up) whose reported week-56 analysis is within-arm and observational after drug discontinuation: LOW.
- Assessment
- Version 2 · Two reviewers differed; settled by a recorded ruling · Nov 7, 2026
Study facts come from the paper. Population match, weight-loss explanation and study tier are our judgments, made against the reference group of healthy normal-weight adults aged 55–75.
In this randomized, double-blind trial, people with HIV-associated lipohypertrophy took semaglutide or placebo for 32 weeks and were then followed after stopping, through week 56. Between weeks 32 and 56 the former semaglutide group regained weight, waist size, body fat and visceral fat, and its glycaemic indices and insulin resistance worsened, though net reductions in weight, BMI and waist circumference remained against baseline; the placebo group stayed relatively stable. Only 80 of 108 randomized participants completed follow-up, and the week-56 comparison is within the semaglutide group.
01Findings
What the study reported
- Drugs
- Semaglutide
- Treatment duration
- 32 weeks
- Comparator
- placebo
- Primary outcome
- adipose tissue quantity by body compartment at week 56, after discontinuation
- Effect
- No numbers given. After stopping, the semaglutide group regained body weight, BMI, waist, total fat and visceral fat between weeks 32 and 56 with worsening glycaemic indices and insulin resistance; net reductions in weight, BMI and waist were retained at week 56 vs baseline; placebo was relatively stable.
- 95% confidence interval
- Not extracted
- Follow-up
- observational follow-up through week 56
- Adverse events
- not reported in abstract
- Limitations
- The week-56 analysis compares the semaglutide group with its own baseline and week-32 values during unblinded observational follow-up after stopping, and only 80 of 108 randomized participants completed it; the population is people with HIV-associated lipohypertrophy.
Who was studied
- Baseline condition
- HIV-associated lipohypertrophy
- Sample size
- 108
- Inclusion exclusion
- people with HIV and HIV-associated lipohypertrophy
Study quality details
- Study design
- Randomized controlled trial
- Sample size
- 108
- Randomization
- yes
- Blinding
- double-blind
- Comparator
- placebo
- Follow up duration
- observational follow-up through week 56
- Outcome type
- intermediate
- Replication
- not assessed
- Consistency with other evidence
- not assessed
- Population applicability
- INDIRECT
- Statistical precision
- no CI reported; 80 of 108 completed the posttreatment phase
- Risk of bias
- not assessed
- Peer review status
- yes
02Funding
Funding and conflicts
- Funding
- not reported in abstract
- Industry funded
- Unclear
- Manufacturer
- not stated in source
- Sponsor role
- not reported in abstract
- Author conflicts
- One author has advised Gilead Sciences and Theratechnologies; all other authors report no potential conflicts.
- Independent replication
- unknown
Funding is shown on every study and never used to score it.
04Source
The source, as retrieved
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.
Where this record came from
| Source | Retrieved | Identifier |
|---|---|---|
| pubmed | Oct 25, 2026 | 42921178 first ingestion |
| pubmed | Nov 1, 2026 | 42921178 duplicate matched on doi |
| owner-review | Nov 6, 2026 | reviewed_by set to Carrie Schluter (2026-11-05) on the owner's own confirmation. The assessment is unchanged and still the auto-classifier's, so its extracted values stay withheld under the 2026-10-18 decision. |
| pubmed | Nov 8, 2026 | 42921178 duplicate matched on doi |