Do reductions in risk of cardiorenal events with SGLT2 inhibitors in type 2 diabetes vary with baseline characteristics?
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RESEARCH LETTER
Do reductions in risk of cardiorenal events with SGLT2 inhibitors in type 2 diabetes vary with baseline characteristics? A meta-analysis Mei Qiu
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Shu-Yan Liu
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Jin-Song Gu3 Kai-Kai Li4 Ling-Lin Li5 Liang-Liang Ding ●
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Received: 28 January 2020 / Accepted: 18 May 2020 © Springer Science+Business Media, LLC, part of Springer Nature 2020
Large cardiovascular (CV) outcome trials demonstrated sodium glucose cotransporter 2 inhibitors (SGLT2is) could significantly reduce cardiorenal events in type 2 diabetic adults. However, the effects of SGLT2is on cardiorenal endpoints in many diabetic subpopulations are undefined because of the following two main reasons. First, the effects of baseline characteristics on cardiorenal events reduced by SGLT2is are controversial across different trials. For instance, most trials showed the effects of baseline characteristics on major adverse cardiovascular events (MACE) reduced by SGLT2is were not significant, whereas some trials revealed the significant effects of duration of diabetes [1], beta-blocker and diuretic use [2], and age and glycated hemoglobin [3] on MACE reduced by SGLT2is in type 2 diabetes. Second, individual trials do not have enough statistical power to evaluate the effects of SGLT2is in some diabetic subpopulations. For instance, dapagliflozin [1] was not observed to significantly reduce CV death or hospitalization for heart failure (HHF) in most diabetic subgroups defined by region, while canagliflozin [4] was not observed to significantly reduce renal composite endpoint in diabetic patients with an estimated glomerular filtration rate (eGFR) ≥60 mL/min/1.73 m2. Therefore, we conducted this meta-analysis to assess the efficacy of SGLT2is on three critical endpoints (i.e.,
MACE, CV death or HHF, and renal composite endpoint) in various diabetic subgroups defined by 17 factors.
Methods
Supplementary information The online version of this article (https:// doi.org/10.1007/s12020-020-02359-5) contains supplementary material, which is available to authorized users.
We searched PubMed and Embase through February 19, 2020 using a pre-planned search strategy (ESM 1, pp 1–2). We included randomized, controlled, event-driven, and CV or kidney outcome trials which evaluated the efficacy of SGLT2is on cardiorenal endpoints in at least one subgroup of type 2 diabetic adults. Three endpoints of interest were MACE, CV death, or HHF, and renal composite endpoint, and their definitions are detailed in ESM 1 (p 3). Subgroups defined by 17 factors of interest were pre-specified in the study protocol, and 3 key factors among them were history of CV disease, history of heart failure (HF), and prevalent CKD. CKD were defined as an eGFR
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