Background: Epicardial adipose tissue (EAT) is an emerging cardio-metabolic risk factor that has been shown to correlate with adverse cardiovascular outcomes through potential local and systemic effects. Consequently, EAT has been proposed as a therapeutic target. The biguanide, metformin, and Sodium-glucose Cotransporter-2 inhibitors have been reported to improve cardiovascular outcomes. We have investigated the effects of both metformin and dapagliflozin, on EAT in patients with prediabetes and type 2 diabetes respectively.
Methods: EAT area measurements were performed blindly on cine 4 chamber views during the end diastolic phase of the cardiac cycle at baseline and at the end of study treatment using CMR scans in patients that participated in two randomized double-blinded placebo controlled trials: (1) MET-REMODEL (ClinicalTrials.gov. NCT02226510) (n=68 patients, mean age 65 ± 8 y; mean BMI 31.9 ± 3.6 kg/m²) with prediabetes and /or insulin resistance who received either metformin (2g /day) or placebo for 12 months and (2) REFORM (ClinicalTrial.gov NCT02397421) (n=56 patients, mean age 67 ± 7 y; mean BMI 32.5± 5.3 kg/m²) with chronic heart failure and type 2 diabetes who received either dapagliflozin (10mg/day) or placebo for 12 months respectively.
Results: Metformin treatment in the METREMODEL trial reduced body weight significantly by 4.2kgs (p=0.001).but did not reduce EAT area (metformin -0.1 ± 3.8 cm² vs. placebo -0.5 ± 2.9 cm² p= 0.7). In the REFORM trial, dapagliflozin reduced body weight significantly by -1.9 kg (p= 0.054) with no significant reduction in EAT area (dapagliflozin -1.00 ± 3.6 cm² vs. placebo -0.7 ± 3.1 p=0.8).
Conclusion: In prediabetes and type 2 diabetes, we found that metformin and dapagliflozin treatment resulted in significant weight loss but had no significant effect on EAT. Our findings suggest that the reported cardiovascular benefits of these two diabetic therapies are not likely to be mediated by effects on EAT.
S. Al-Talabany: None. J. Weir-McCall: None. M. Mohan: None. J.S. Singh: None. I. Mordi: None. S.J. Gandy: None. F. Khan: None. A. Choy: None. J.G. Houston: None. E. Pearson: Speaker's Bureau; Self; Eli Lilly and Company. J. George: None. A.D. Struthers: Research Support; Self; AstraZeneca. Advisory Panel; Self; AstraZeneca. C.C. Lang: None.