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Liraglutide Myocardial Effects in Type 2 Diabetes
Quick Takes
- Compared with pioglitazone, 4 months of treatment with liraglutide resulted in significant increments in myocardial stress perfusion and myocardial energetics in T2D patients who had normal cardiac function and no established CVD.
- Furthermore, these improvements in myocardial perfusion and energetics with liraglutide were accompanied by significantly increased 6-minute walk distance.
- Additional studies are indicated to assess the relative contributions of these effects to the benefits of GLP-1 agonists on CV outcomes in patients with T2D.
Study Questions:
What are the efficacies of increasing insulin secretion versus decreasing insulin resistance (IR) strategies for improving myocardial perfusion, energetics, and function in type 2 diabetes (T2D)?
Methods:
Forty-one eligible patients with T2D and no known prior cardiovascular disease (CVD) were randomized in a 1:1 ratio to liraglutide or pioglitazone for a 16-week treatment period followed by an 8-week washout and a further 16-week treatment period for the second drug. Participants underwent rest and dobutamine stress 31phosphorus magnetic resonance spectroscopy followed by cardiac magnetic resonance (CMR) scans. The CMR protocol consisted of rest and dobutamine stress cine imaging, perfusion imaging, and late gadolinium enhanced imaging immediately before and after each treatment arm for measuring the myocardial energetics index phosphocreatine to adenosine triphosphate ratio (PCr/ATP), myocardial perfusion (rest, dobutamine stress myocardial blood flow [MBF] and myocardial perfusion reserve [MPR]), left ventricular (LV) volumes, and systolic and diastolic function (mitral in-flow E/A ratio). Six-minute walk test was used for functional assessments. The primary endpoint was change in myocardial perfusion as measured by the MPR and global stress-MBF after treatment with liraglutide and pioglitazone. The matched-pairs paired t-test was used to evaluate differences between pre-treatment and post-treatment data (i.e., before vs. after pioglitazone administration and before vs. after liraglutide administration).
Results:
Pioglitazone treatment resulted in significant increases in LV mass (96 g [68-105] to 105 g [74-115]; p = 0.003) and mitral-inflow E/A ratio (1.04 [0.62-1.21] to 1.34 [0.70-1.54]; p = 0.008), and a significant reduction in LV concentricity index (0.79 [0.61-0.85] to 0.73 [0.56-0.79] mg/mL; p = 0.04). Liraglutide treatment increased stress MBF (1.62 mL/g/min [1.19-1.75] to 2.08 mL/g/min [1.57-2.24]; p = 0.01) and MPR (2.40 [1.55-2.68] to 2.90 [1.83-3.18]; p = 0.01). Liraglutide treatment also significantly increased the rest (1.47 [1.17-1.58] to 1.94 [1.52-2.08]; p = 0.00002) and stress PCr/ATP ratio (1.32 [1.05-1.42] to 1.58 [1.19-1.71]; p = 0.004) and 6-minute walk distance (488 m [458-518] to 521 m [481-561]; p = 0.009).
Conclusions:
The authors report that liraglutide treatment resulted in improved myocardial perfusion, energetics, and 6-minute walk distance in patients with T2D, while pioglitazone showed no effect on these parameters.
Perspective:
This randomized cross-over trial reports that, compared with pioglitazone, 4 months of treatment with liraglutide resulted in significant increments in myocardial stress perfusion and myocardial energetics in T2D patients who had normal cardiac function and no established CVD. Furthermore, these improvements in myocardial perfusion and energetics with liraglutide were accompanied by significantly increased 6-minute walk distance. Additional studies are indicated to assess the relative contributions of these effects to the benefits of glucagon-like peptide-1 (GLP-1) receptor agonists on CV outcomes in patients with T2D.
Clinical Topics: Noninvasive Imaging, Magnetic Resonance Imaging, Diabetes and Cardiometabolic Disease
Keywords: Diabetes Mellitus, Type 2, Liraglutide, Magnetic Resonance Imaging
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