This paper, co-authored by Associate Professor Roy Rasalam (Principal Investigator at AusTrials Sunshine in Melbourne), systematically reviews randomized controlled trials assessing effects of sodium–glucose cotransporter 2 inhibitors (SGLT2is) on hospitalization for heart failure (HHF) and cardiac structure/function and explore randomized controlled trial (RCT)-derived evidence for SGLT2i efficacy mechanisms in heart failure (HF).
This review found that in seven trials [3730–17 160 patients; low risk of bias (RoB)], SGLT2is significantly reduced the relative risk of HHF by 27–39% vs. placebo, including in two studies in patients with HF with reduced ejection fraction with or without type-2 diabetes mellitus (T2DM). Improvements in conventional cardiovascular risk factors, including glycaemic levels, cannot account for these effects.
Five trials (56–105 patients; low RoB) assessed the effects of 6–12 months of SGLT2i treatment on left ventricular structure/function; four reported significant improvements vs. placebo, and one did not. Five trials (low RoB) assessed SGLT2i treatment effects on serum N-terminal pro B-type natriuretic peptide levels; significant reductions vs. placebo were reported after 8–12 months (two studies; 3730–4744 patients) but not ≤12 weeks (three studies; 80–263 patients).
Limited available RCT-derived evidence suggested various possible cardioprotective SGLT2i mechanisms, including improved haemodynamics and vascular function, enhanced erythropoiesis, reduced tissue sodium and epicardial fat/inflammation, decreased sympathetic tone, and beneficial changes in cellular energetics.
To read more on this paper, visit: https://onlinelibrary.wiley.com/doi/10.1002/ehf2.13483