Dapagliflozin did not significantly change myocardial glucose uptake but significantly improved myocardial flow reserve compared to placebo in patients with type 2 diabetes and stable coronary artery disease.
RCT (n=16)
Double-blind
1:1
No
Does dapagliflozin improve myocardial glucose uptake and myocardial flow reserve in patients with type 2 diabetes and stable coronary artery disease?
In patients with type 2 diabetes and stable coronary artery disease, 4 weeks of dapagliflozin treatment significantly improved myocardial flow reserve and reduced resting myocardial blood flow, suggesting a potential mechanism for its cardiovascular benefits through improved coronary microvascular function.
p-value: p=0.41
Abstract Objective Cardiovascular (CV) outcome trials have shown that in patients with type 2 diabetes (T2D), treatment with sodium-glucose cotransporter-2 inhibitors (SGLT-2i) reduces CV mortality and hospital admission rates for heart failure (HF). However, the mechanisms behind these benefits are not fully understood. This study was performed to investigate the effects of the SGLT-2i dapagliflozin on myocardial perfusion and glucose metabolism in patients with T2D and stable coronary artery disease (coronary stenosis ≥ 30% and 6 months) but no HF. Methods This was a single-center, prospective, randomized, double-blind, controlled clinical trial including 16 patients with T2D randomized to SGLT-2i dapagliflozin (10 mg daily) or placebo. The primary outcome was to detect changes in myocardial glucose uptake (MGU) from baseline to 4 weeks after treatment initiation by (18)F2-deoxy-2-fluoro-D-glucose (FDG) PET/CT during hyperinsulinemic euglycemic clamp. The main secondary outcome was to assess whether the hypothetical changes in MGU were associated with changes in myocardial blood flow (MBF) and myocardial flow reserve (MFR) measured by 13 N-ammonia PET/CT. The study was registered at eudract.ema.europa.eu (EudraCT No. 2016-003614-27) and ClinicalTrials.gov (NCT 03313752). Results 16 patients were randomized to dapagliflozin (n = 8) or placebo (n = 8). The groups were well-matched for baseline characteristics (age, diabetes duration, HbA1c, renal and heart function). There was no significant change in MGU during euglycemic hyperinsulinemic clamp in the dapagliflozin group (2.22 ± 0.59 vs 1.92 ± 0.42 μmol/100 g/min, p = 0.41) compared with the placebo group (2.00 ± 0.55 vs 1.60 ± 0.45 μmol/100 g/min, p = 0.5). Dapagliflozin significantly improved MFR (2.56 ± 0.26 vs 3.59 ± 0.35 p = 0.006 compared with the placebo group 2.34 ± 0.21 vs 2.38 ± 0.24 p = 0.81; p int = 0.001) associated with a reduction in resting MBF corrected for cardiac workload (p = 0.005; p int = 0.045). A trend toward an increase in stress MBF was also detected (p = 0.054). Conclusions SGLT-2 inhibition increases MFR in T2D patients. We provide new insight into SGLT-2i CV benefits, as our data show that patients on SGLT-2i are more resistant to the detrimental effects of obstructive coronary atherosclerosis due to increased MFR, probably caused by an improvement in coronary microvascular dysfunction. Trial registration EudraCT No. 2016-003614-27; ClinicalTrials.gov Identifier: NCT03313752
Leccisotti et al. (Sat,) conducted a rct in Type 2 diabetes and stable coronary artery disease (n=16). Dapagliflozin vs. Placebo was evaluated on Changes in myocardial glucose uptake (MGU) from baseline to 4 weeks (p=0.41). Dapagliflozin did not significantly change myocardial glucose uptake but significantly improved myocardial flow reserve compared to placebo in patients with type 2 diabetes and stable coronary artery disease.