Effect of 26 Weeks of Liraglutide Treatment on Coronary Artery Inflammation in Type 2 Diabetes Quantified by [ 64 Cu]Cu-DOTATATE PET/CT: Results from the LIRAFLAME Trial.

Background: Quantification of coronary artery inflammation and atherosclerosis remains a challenge in high-risk individuals. In this study we sought to investigate if the glucagon like peptide-1 receptor agonist liraglutide has a direct anti-inflammatory effect in the coronary arteries using positron emission tomography (PET) with a radioactive tracer targeting activated macrophages in the vessel-wall.
Methods: Thirty randomly selected participants with type 2 diabetes from the placebo-controlled trial LIRAFLAME were enrolled in this sub-study. Participants were, prior to enrollment in this sub-study, randomized to either treatment with daily liraglutide (n=15) or placebo (n=15). Both groups underwent a combined [ ⁶⁴ Cu]Cu-DOTATATE positron emission tomography and computed tomography scan of the heart at baseline and after 26 weeks of treatment. Coronary artery uptake of [ ⁶⁴ Cu]Cu-DOTATATE were measured as maximum standardized uptake values (SUV _max ); and means of the maximum values (mSUV _max ), both values were calculated at the level of each participant and each individual coronary-segment.
Results: SUV _max and mSUV _max values decreased significantly in the liraglutide group both at the participant level (SUV _max : p=0.013; mSUV _max : p=0.004) and at the coronary-segment level (SUV _max : p=0.001; mSUV _max : p<0.0001). No change was observed in the placebo group neither at the participant level (SUV _max : p=0.69; mSUV _max : p=0.67) or at the coronary-segment level (SUV _max : p=0.49; mSUV _max : p=0.30). When comparing the mean change in uptake values between the two groups at both the participant level (SUV _max : p=0.076; mSUV _max : p=0.077) and the coronary segment level (SUV _max : p=0.13; mSUV _max : p=0.11) a borderline significant difference was observed. Baseline SUV _max [ ⁶⁴ Cu]Cu-DOTATATE uptake values showed a weak positive correlation with the inflammatory biomarker high-sensitivity c-reactive protein (τ =0.26, p=0.045).
Conclusion: Liraglutide treatment for 26-weeks caused a significant reduction in [ ⁶⁴ Cu]Cu-DOTATATE uptake in the coronary arteries whereas this was not seen in the placebo treated group. In addition, [ ⁶⁴ Cu]Cu-DOTATATE PET/CT as a marker of coronary inflammation correlated with the systemic inflammation marker hs-CRP.
Competing Interests: AK has received consultancy fees from Novo Nordisk and is an inventor on a patent of [64Cu]Cu-DOTATATE. RR, BS, TH, and PR have shares in Novo Nordisk A/S. BS and EZ are now employees of Novo Nordisk A/S. PR has received the following: Consultancy and/or speaking fees (to Steno Diabetes Center Copenhagen) from AbbVie, Astellas, AstraZeneca, Bayer, Boehringer Ingelheim, Bristol-Myers Squibb, Eli Lilly, MSD, Novo Nordisk and Sanofi Aventis; Research grants to institution from AbbVie, AstraZeneca and Novo Nordisk. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
(Copyright © 2021 Jensen, Zobel, von Scholten, Rotbain Curovic, Hansen, Rossing, Kjaer and Ripa.)