Abstract

Almost all clinical practice guidelines recommend that SGLT2 inhibitors are used as second-line pharmacotherapy in people with type 2 diabetes and chronic kidney disease or heart failure if they do not achieve sufficient glucose control with metformin. We sought to assess whether the effects of SGLT2 inhibitors on cardiovascular, kidney and mortality outcomes are consistent with and without concomitant metformin use.We conducted a meta-analysis of event-driven, randomized, placebo-controlled SGLT2 inhibitor trials that reported cardiovascular, kidney or mortality outcomes by baseline metformin use. Treatment effects reported as hazards ratios (HR) and 95% confidence intervals (CI) were pooled using random effects meta-analysis. The main outcomes in this analysis were (1) major adverse cardiovascular events (MACE) and (2) hospitalized heart failure (HHF) or cardiovascular death.We included six trials of four SGLT2 inhibitors that enrolled 51,743 participants. Baseline metformin use varied from 21% in DAPA-HF to 82% in DECLARE-TIMI 58. SGLT2 inhibitors reduced the risk of MACE, with and without concomitant metformin use (HR 0.93, 95% CI 0.87-1.00 and HR 0.82, 95% CI 0.71-0.86 respectively; P-heterogeneity=0.14). There were also clear and separate reductions in HHF or cardiovascular death with SGLT2 inhibitors irrespective of metformin use (HR 0.79, 95% CI 0.73-0.86 and HR 0.74, 95% CI 0.63-0.87 respectively; P-heterogeneity=0.48), as well as for major kidney outcomes and all-cause mortality (all P-heterogeneity>0.40).Treatment with SGLT2 inhibitors results in clear and consistent reductions in cardiovascular, kidney and mortality outcomes regardless of whether patients are receiving or not receiving metformin. This article is protected by copyright. All rights reserved.

View details for DOI 10.1111/dom.14226

View details for PubMedID 33043620