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.