• Mei-Chuan Lee, Yi-Ming Hua, Chun-Ting Yang, Fang-Hsiu Kuo, Wei-Ting Chang, Hsin-Ju Tang, Siong TohHanHInstitute of Clinical Medicine, College of Medicine, National Cheng Kung University, Tainan, Taiwan.Department of Intensive Care Medicine, Chi Mei Medical Center, Tainan, Taiwan.Department of Health and Nutrition, Chia Nan University of Pharm, Yu-Min Lin, Sih-Yao Chen, Hung-Yu Chang, and Chia-Te Liao.
• Department of Pharmacy, Chi Mei Medical Center, Tainan, Taiwan.
• Medicine (Baltimore). 2022 Dec 23; 101 (51): e32489e32489.

BackgroundSome sodium-glucose co-transporter-2 (SGLT2) inhibitors showed benefits on heart failure (HF), but different SGLT2/SGLT1 selectivity might influence the treatment effect. This study aimed to meta-analyze the treatment effects of SGLT2 inhibitors and the diversity of receptor selectivity for patients with and without HF.MethodsRandomized controlled trials were searched in PubMed, Embase, Cochrane databases and ClinicalTrials.gov registry from inception to October 2020. The interest outcomes were analyzed with random-effects models and presented with a risk ratio (RR) and 95% confidence interval (CI). Subgroup analyses examined the treatment effects among SGLT2 inhibitors with different SGLT2/SGLT1 selectivity.ResultsThe final analyses included 10 trials and 52,607 patients. The RR of total cardiovascular (CV) death or hospitalization for HF (HHF) between SGLT2 inhibitors and placebo was 0.79 (95% CI 0.74-0.84, I2 = 31%). With SGLT2 inhibitors, HF patients had reduced mortality risks (RR 0.89, 95% CI 0.80-0.99, I2 = 0), and non-HF patients had lower risks of major adverse CV events (RR 0.92, 95% CI 0.85-0.99, I2 = 0). The risk reduction of HHF was consistent in groups of HF (RR 0.72, 95% CI 0.64-0.80, I2 = 8%) and non-HF (RR 0.74, 95% CI 0.61-0.89, I2 = 0), but the effect of the low SGLT2/SGLT1 selectivity inhibitor was insignificant in non-HF patients.ConclusionThe efficacy of SGLT2 inhibitors on risk reduction of total CV death or HHF is consistent with the previous studies. The regimen is beneficial for reducing mortality in patients with HF and major adverse CV events in those without HF. Different SGLT2/SGLT1 selectivity may differ in the treatment effects in patients with and without HF.Copyright © 2022 the Author(s). Published by Wolters Kluwer Health, Inc.

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