Limitations and strengths of the study
EVENTS, DISEASES
This study has limitations. The number of subjects recruited was relatively small, which probably explains why some results trended toward, but did not reach statistical significance, limiting our conclusions to speculation. However, the reduction in EAT thickness and in EAT FDG SUV are statistically significant, and an increased study sample size would only have reinforced the significanceFurther, there is no measurement of local inflammatory markers, which could have supported our interpretation of the potential mechanism explaining the correlation between the reduction of EAT glucose uptake and reduction of myocardial blood flow. Lastly, localization of FDG uptake is difficult due to the small size of the coronary arteries, coronary motion, as well as increased FDG uptake in the myocardium during the hyperinsulinemic euglycemic clamp. Therefore, correction of cardiac and respiratory motion using dual-gated PET/CTA cardiac imaging may improve the detection of EAT FDG uptake [On the other hand, our study also has many strengths. The use of a sophisticated and gold standard technique to synergically assess the morphology and metabolism of adipose tissue depots and myocardial blood flow allowed us to provide a pathophysiologic explanation for the beneficial effects of SGLT-2i treatment for CV diseases. Importantly, this is the first study to explore visceral and subcutaneous adipose tissue depots in the same subjects in response to SGLT-2i treatment. This allowed us to demonstrate the selective effect of a 4-week SGLT-2i treatment on EAT, explaining the rapid efficacy of these drugs in providing protection from CV events.