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Sodium‐glucose co‐transporter‐2 inhibitors with and without metformin: A meta‐analysis of cardiovascular, kidney and mortality outcomes
Author(s) -
Neuen Brendon L.,
Arnott Clare,
Perkovic Vlado,
Figtree Gemma,
Zeeuw Dick,
Fulcher Greg,
Jun Min,
Jardine Meg J.,
Zoungas Sophia,
Pollock Carol,
Mahaffey Kenneth W.,
Neal Bruce,
Heerspink Hiddo J. L.
Publication year - 2021
Publication title -
diabetes, obesity and metabolism
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.445
H-Index - 128
eISSN - 1463-1326
pISSN - 1462-8902
DOI - 10.1111/dom.14226
Subject(s) - medicine , metformin , mace , concomitant , hazard ratio , meta analysis , lower risk , pharmacology , confidence interval , insulin , myocardial infarction , percutaneous coronary intervention
Aim To assess whether the effects of sodium‐glucose co‐transporter‐2 (SGLT2) inhibitors on cardiovascular, kidney and mortality outcomes are consistent with and without concomitant metformin use. Material and methods 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 (HRs) and 95% confidence intervals (CIs), were pooled using random‐effects meta‐analysis. The main outcomes in this analysis were (i) major adverse cardiovascular events (MACE) and (ii) hospitalization for heart failure (HHF) or cardiovascular death. Results We included six trials of four SGLT2 inhibitors that enrolled a total of 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). Conclusion 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.