Zelniker TA, et al. - In patients with type 2 diabetes, researchers evaluated the scale of the impact of sodium-glucose cotransporter-2 inhibitors (SGLT2i) on specific cardiovascular and renal outcomes by conducting a systematic review and meta-analysis of cardiovascular outcome trials. They also assessed if heterogeneity is based on key baseline features. Findings suggest moderate benefits of SGLT2i for atherosclerotic major adverse cardiovascular events (myocardial infarction, stroke, or cardiovascular death) that appear to be limited to patients with established cardiovascular atherosclerotic disease. However, they have strong advantages in decreasing hospitalization for heart failure and renal disease progression regardless of existing atherosclerotic cardiovascular disease or a history of heart failure.

Methods

• In patients with type 2 diabetes, investigators conducted a systematic review and meta-analysis of randomized, placebo-controlled, cardiovascular outcome trials of SGLT2i.
• For trials published up to September 24, 2018, they searched PubMed and Embase.
• Major adverse cardiovascular events, the composite of cardiovascular death or hospitalization for heart failure, and progression of renal disease were the included 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, 2,028 cardiovascular deaths or hospitalization for heart failure events, and 766 renal composite outcomes. SGLT2i reduced major adverse cardiovascular events by 11% (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 observed a reduction in the risk of cardiovascular death or hospitalization 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.
• Findings revealed 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 discovered a variation in the magnitude of benefit of SGLT2i with baseline renal function, with greater reductions in hospitalizations 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.