Exercise, but not liraglutide, linked to decreased atherosclerosis development

Key Points

• • In adults with obesity who had recently lost weight, exercise during weight-loss maintenance lowered the progression of atherosclerosis.

• • In contrast, liraglutide (a GLP-1 receptor agonist) did not show this effect in the same group.

Study Overview

A clinical trial presented at the European Association for the Study of Diabetes (EASD) Annual Meeting evaluated how exercise and liraglutide affect weight-loss maintenance and cardiovascular health.

• • Participants: 195 adults with obesity but without diabetes (average age 43 years; 64% women).

• • Initial Phase: All participants followed a low-calorie diet for 8 weeks, leading to an average weight loss of 13.1 kg.

• • Randomization: Afterward, they were assigned to one of four groups for 52 weeks:
  • Exercise + liraglutide
  • Exercise only
  • Liraglutide only
  • Placebo

Scientific Rationale

According to Signe Sørensen Torekov, PhD (University of Copenhagen), obesity and physical inactivity promote inflammation and endothelial dysfunction, both of which drive early atherosclerosis and cardiovascular disease.

• • Exercise improves body composition, lowers inflammation, and enhances vascular function.

• • GLP-1 receptor agonists, such as liraglutide, also reduce inflammation and support weight loss.

• • The hypothesis: both strategies might reduce atherosclerosis progression.

Outcomes Measured

• • Primary outcome: Change in carotid intima-media thickness (CIMT), a marker of early atherosclerosis.

• • Secondary outcomes: Changes in biomarkers of inflammation and endothelial function.

Results

Body Composition

• • Initial rapid weight loss caused both fat and muscle loss.

• • • • Combined treatment (exercise + liraglutide): Showed the greatest fat loss and a small increase in muscle mass.
        • • Liraglutide group: Further fat reduction but no muscle gain.
            • • Exercise groups: Gained back lean muscle while continuing to lose fat.Over the following year:

Atherosclerosis (CIMT)

• • Exercise groups: CIMT decreased by –0.024 mm, nearly three times more than in non-exercise groups. This corresponds to an estimated 25% lower risk of cardiovascular disease.

• • Liraglutide groups: No meaningful difference compared with placebo.

Inflammation & Endothelial Dysfunction

Only exercise showed significant reductions in pro-inflammatory and endothelial markers:

• • Interleukin-6 (IL-6) ↓

• • Interferon-gamma ↓

• • Soluble ICAM-1 ↓

• • Soluble VCAM-1 ↓

• • Tissue plasminogen activator ↓

Liraglutide did not produce similar improvements.

Conclusions

• • Exercise, not liraglutide, reduced subclinical atherosclerosis (CIMT).

• • The benefits were linked to reduced inflammation and improved vascular function.

• • Combination therapy (exercise + liraglutide) provided the greatest fat loss, but only exercise contributed to cardiovascular risk reduction.

Dr. Torekov summarized:

• • Exercise after weight loss helps preserve lean mass, reduce fat, and protect cardiovascular health.

• • GLP-1 drugs support fat loss but do not substitute for exercise in preventing atherosclerosis.

This work earned the Best Abstract Prize from the EASD Early Career Academy.

Bottom Line: Exercise during and after weight loss not only helps maintain healthy body composition but also directly reduces cardiovascular risk factors, whereas liraglutide alone does not reduce subclinical atherosclerosis.