Meta-Analysis on the Safety and Cardiorenal Efficacy of SGLT2 Inhibitors in Patients Without T2DM.

Lu-Feng Li,Mei Qiu,Liang-Liang Ding,Ze-Lin Zhan

doi:10.3389/fcvm.2021.690529

Abstract

The cardiorenal benefits of sodium-glucose cotransporter 2 (SGLT2) inhibitors in patients with type 2 diabetes mellitus (T2DM) are established, whereas those in patients without T2DM are not established. We sought to assess the cardiorenal efficacy and safety of SGLT2 inhibitors in non-T2DM patients by performing a meta-analysis based on the subgroup data of non-T2DM patients from relevant secondary analysis articles in which subgroup analyses were done according to the status of diabetes. Compared to placebo, SGLT2 inhibitors significantly reduced heart failure hospitalization [risk ratio (RR) 0.70, 95% confidence interval (CI) 0.59–0.83] and kidney-specific composite outcome (RR 0.55, 95% CI 0.40–0.75) and increased Kansas City Cardiomyopathy Questionnaire total score by 1.15 (95% CI 1.05–1.25) in patients without T2DM with heart failure (HF) or chronic kidney disease (CKD), whereas gliflozins did not significantly affect cardiovascular death, all-cause mortality, volume depletion, fracture, and amputation in this vulnerable population. There was no event of major hypoglycemia or diabetic ketoacidosis observed in the non-T2DM subgroup in included trials. These findings will further prompt gliflozins to be used for the prevention of HF and renal failure events and for the improvement of life quality in patients without T2DM with HF or CKD.

Highlights

According to the evidence from large trials assessing the effects of sodium-glucose cotransporter 2 (SGLT2) inhibitors on cardiovascular or renal outcomes, the cardiorenal benefits of SGLT2 inhibitors have already been extended from patients with type 2 diabetes mellitus (T2DM) [1,2,3,4,5] to patients with heart failure (HF) [6, 7] and those with chronic kidney disease (CKD) [8]
The six efficacy endpoints we assessed in this meta-analysis were as follows: a composite of hospitalization for heart failure (HHF) or cardiovascular death (CVD), CVD, HHF, all-cause mortality (ACM), kidney-specific composite outcome (KSCO), and change in Kansas City Cardiomyopathy Questionnaire (KCCQ) total score
There was no one event of major hypoglycemia or diabetic ketoacidosis observed in the nonT2DM subgroup in all the included trials. This is the first meta-analysis that fully assessed the safety and cardiorenal efficacy of SGLT2 inhibitors in patients without T2DM. This meta-analysis revealed that SGLT2 inhibitors vs. placebo significantly reduced HHF and KSCO and increased KCCQ total score in patients without T2DM and did not significantly affect CVD and ACM, while SGLT2 inhibitors lowered the risks of serious adverse event and kidney adverse event in this vulnerable population and did not lead to the increased risks of volume depletion, fracture, amputation, major hypoglycemia, and diabetic ketoacidosis

Summary

Introduction

According to the evidence from large trials assessing the effects of sodium-glucose cotransporter 2 (SGLT2) inhibitors on cardiovascular or renal outcomes, the cardiorenal benefits of SGLT2 inhibitors have already been extended from patients with type 2 diabetes mellitus (T2DM) [1,2,3,4,5] to patients with heart failure (HF) [6, 7] and those with chronic kidney disease (CKD) [8]. The outcome data of gliflozins in non-T2DM patients have recently been reported in three articles [12,13,14] in which subgroup analyses were conducted according to the status of diabetes.

Results

Conclusion