Effect of Liraglutide on Vascular Inflammation Evaluated by [⁶⁴Cu]DOTATATE

• Main Authors: Emilie H. Zobel, Rasmus S. Ripa, Bernt J. von Scholten, Viktor Rotbain Curovic, Lars Jorge Diaz, Tine W. Hansen, Peter Rossing, Andreas Kjaer
• Format: Article
• Language: English
• Published: MDPI AG 2021-08-01
• Series: Diagnostics
• Subjects: GLP-1 RA; vascular inflammation; PET; type 2 diabetes
• Online Access: https://www.mdpi.com/2075-4418/11/8/1431

Quantification of vascular inflammation before and after treatment with glucagon-like peptide-1 receptor agonists (GLP-1 RAs) may help reveal mechanistic pathways underlying the cardiovascular benefits of these drugs. We assessed change in vascular inflammation in the carotid arteries over 26 weeks by copper-64-labeled [1,4,7,10-tetraazacyclododecane-N,N′,N″,N‴-tetraacetic acid]-D-Phe1, Tyr3-octreotate ([⁶⁴Cu]DOTATATE) PET in 30 participants included in a substudy of a double-blind trial where persons with type 2 diabetes (T2D) were randomized to liraglutide (<i>n</i> = 15) or placebo (<i>n</i> = 15) for 26 weeks. Mean age (SD) was 66.4 (7.2) years, HbA_1c 56.4 (9.2) mmol/mol and BMI 28.9 (4.6) kg/m². Weight and HbA_1c were significantly reduced by liraglutide vs. placebo (<i>p</i> ≤ 0.01). The [⁶⁴Cu]DOTATATE uptake (mean standardized uptake values) was significantly reduced in the liraglutide-treated group (−0.11 [95% confidence interval −0.19 to −0.03], <i>p</i> = 0.01) and not changed significantly in the placebo group (−0.07 [−0.14 to 0.01], <i>p</i> = 0.08). The mean difference between groups did not reach significance (−0.04 [−0.15 to 0.07], <i>p</i> = 0.44). In conclusion, [⁶⁴Cu]DOTATATE uptake was reduced in persons with T2D treated with liraglutide. However, the reduction compared to placebo did not reach statistical significance, perhaps due to limited power. A reduction in vascular inflammation with liraglutide could help explain the cardiovascular protection observed with GLP-1 RAs in outcome studies but warrants further and larger studies.