Zelniker TA, et al. - Researchers assessed the magnitude of effect of sodium-glucose cotransporter-2 inhibitors (SGLT2i) on specific cardiovascular and renal outcomes. They also assessed whether or not heterogeneity is based on key baseline characteristics. Findings suggested moderate benefits of SGLT2i on atherosclerotic major adverse cardiovascular events that seem confined to patients with the established atherosclerotic cardiovascular disease. Nonetheless, regardless of existing atherosclerotic cardiovascular disease or a history of heart failure, they have robust benefits on reducing hospitalisation for heart failure and progression of renal disease.

Methods

• Experts conducted a systematic review and meta-analysis of randomised, placebo-controlled, cardiovascular outcome trials of SGLT2i in patients with type 2 diabetes.
• They searched PubMed and Embase for trials published up to Sept 24, 2018.
• A standardised data completed the data search and extraction with form and any discrepancies were resolved by consensus.
• Major adverse cardiovascular events (myocardial infarction, stroke, or cardiovascular death), the composite of cardiovascular death or hospitalisation for heart failure, and progression of renal disease were the efficacy outcomes.
• They pooled the hazard ratios (HRs) with 95% CIs across trials, and efficacy outcomes were stratified by baseline presence of atherosclerotic cardiovascular disease, heart failure, and degree of renal function.

Results

• The data were included from three identified trials and 34,322 patients (60·2% with established atherosclerotic cardiovascular disease), with 3,342 major adverse cardiovascular events, 2028 cardiovascular deaths or hospitalisation sfor heart failure events, and 766 renal composite outcomes.
• Major adverse cardiovascular events were reduced by SGLT2i (HR 0·89 [95% CI 0·83–0·96], p=0·0014), with benefit only seen in patients with atherosclerotic cardiovascular disease (0·86 [0·80–0·93]) and not in those without (1·00 [0·87–1·16], p for interaction=0·0501).
• They noted a reduction in the risk of cardiovascular death or hospitalisation for heart failure by 23% with SGLT2i (0·77 [0·71–0·84], p < 0·0001), with a similar benefit in patients with and without atherosclerotic cardiovascular disease and with and without a history of heart failure.
• Results demonstrated that SGLT2i reduced the risk of progression of renal disease by 45% (0·55 [0·48–0·64], p < 0·0001), with a similar benefit in those with and without atherosclerotic cardiovascular disease.
• They noted a variation in the magnitude of benefit of SGLT2i with baseline renal function, with greater reductions in hospitalisations for heart failure (p for interaction=0·0073) and lesser reductions in progression of renal disease (p for interaction=0·0258) in patients with more severe kidney disease at baseline.