What is the clinical evidence from this study?

Study design: RCT. Population: Obesity (n=130). Intervention: Exercise and/or Liraglutide vs. Placebo with usual activity. Primary outcome: Change in carotid intima-media thickness (cIMT) (7% reduction (Exercise group), 95% CI 2 to 12, p=0.01).

June 25, 2026Nature Metabolism1 citationsOpen Access

Effects of exercise and liraglutide on vascular health and inflammation during weight loss maintenance: a prespecified secondary analysis of the S-LiTE trial

RSRasmus Michael SandsdalUniversity of Copenhagen JHJoachim HoltUniversity of Copenhagen HAHaithem Ghalib Ali AlkhefagieUniversity of Copenhagen

Key Result

During a 52-week weight maintenance phase, exercise alone or in combination with liraglutide significantly reduced carotid intima-media thickness by 7% and 6% respectively, whereas liraglutide alone did not.

Key Points

This study investigates the effects of exercise and liraglutide on vascular health and inflammation during weight loss maintenance.
Secondary analysis of the S-LiTE trial with 130 adults with obesity.
Participants underwent a weight loss plan and were randomized to exercise and/or liraglutide for 52 weeks.
Outcomes included carotid intima-media thickness and pro-inflammatory cytokine levels.
Exercise alone or with liraglutide reduced carotid intima-media thickness and systemic cytokine levels (interleukin-6, interferon-γ).
Combination treatment improved endothelial function biomarkers (sICAM-1, sVCAM-1, tPA).
Liraglutide alone did not show improvements in these outcomes.

Study Design

Type

RCT (n=130)

Blinding

Double-blind

Randomization

1:1:1:1 ratio

Multicenter

Structured PICO

Does exercise and/or liraglutide improve carotid intima-media thickness and inflammatory/endothelial biomarkers in adults with obesity after diet-induced weight loss?

Population

130 adults with obesity who achieved at least 5% weight loss on a low-calorie diet were randomized to 52 weeks of weight maintenance with exercise, liraglutide, both, or placebo.

Intervention

Exercise (≥150 min moderate or 75 min vigorous aerobic exercise/week) and/or liraglutide (up to 3.0 mg subcutaneous once daily) for 52 weeks.

Comparator

Volume-matched placebo with usual activity for 52 weeks.

Outcome

Change in carotid intima-media thickness (cIMT) after 52 weeks of weight maintenance.surrogate

Regular physical activity, with or without liraglutide, reduces carotid intima-media thickness and systemic inflammation during weight loss maintenance in adults with obesity, whereas liraglutide alone does not.

Main Result

Effect estimate: 7% reduction (Exercise group) (95% CI 2 to 12)

p-value: p=0.01

Limitations

Prespecified secondary analysis, requiring caution regarding type I error
cIMT is a surrogate endpoint for vascular health
Initial diet-induced weight loss may have attenuated the weight-loss-dependent effects of liraglutide and exercise
More frequent contact in exercise groups could have led to a Hawthorne effect
Partly supervised exercise intervention may limit direct generalizability to routine clinical settings
Uncertain whether the observed results are sustainable in the long term beyond 1 year

Abstract

Abstract Obesity and inactivity are linked to endothelial dysfunction and atherosclerosis. In this secondary analysis of the S-LiTE trial (ClinicalTrials.gov identifier: NCT04122716 ; EudraCT identifier: 2015–005585-32 ), 130 adults with obesity completed a diet-induced weight loss plan, followed by randomization to weight maintenance with exercise and/or liraglutide for 52 weeks. We show that exercise, alone or in combination with liraglutide, reduces carotid intima-media thickness and systemic pro-inflammatory cytokine levels (interleukin-6 and interferon-γ). Combination treatment also improves endothelial function biomarkers (sICAM-1, sVCAM-1 and tPA). Liraglutide alone shows no such improvements. Overall, regular physical activity, with or without GLP-1R agonists, is essential for promoting vascular health in adults with obesity.

Ask AI

Helpful

Bookmark

View Full Paper