Pleiotropic effects of antidiabetic agents on renal and cardiovascular outcomes: a meta-analysis of randomized controlle
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NEPHROLOGY - ORIGINAL PAPER
Pleiotropic effects of antidiabetic agents on renal and cardiovascular outcomes: a meta‑analysis of randomized controlled trials Api Chewcharat1,2 · Kullaya Takkavatakarn1 · Suramath Isaranuwatchai1,3 · Pisut Katavetin1 · Kearkiat Praditpornsilpa1 · Somchai Eiam‑ong1 · Paweena Susantitaphong1,4 Received: 3 January 2020 / Accepted: 25 May 2020 © Springer Nature B.V. 2020
Abstract Background This meta-analysis was conducted to examine the pleiotropic effects of all available antidiabetic agents except insulin for type 2 diabetes on renal and cardiovascular outcomes. Methods A systematic literature search was performed in PubMed, EMBASE, and Cochrane database to identify randomized-controlled trials which compared the effectiveness between all antidiabetic agents apart from insulin regarding all aspects of renal and cardiovascular outcomes. Random effect model was utilized to compute for hazard ratio. Results Nineteen articles with 140,851 participants were included in this meta-analysis. When compared with placebo, SGLT-2 inhibitors, GLP-1 agonists, and DPP-4 inhibitors exhibited significantly lower hazard ratios of progression of albuminuria. SGLT-2 inhibitors and DPP-4 inhibitors showed a significantly higher hazard ratio of regression of albuminuria. Only SGLT-2 inhibitors illustrated significantly lower hazard ratios of doubling of serum creatinine and incidence of renal replacement therapy (RRT). A significantly lower hazard ratio of composite renal outcome was detected in both SGLT-2 inhibitors and GLP-1 agonists. A significantly lower hazard ratio of all-cause mortality was identified in SGLT-2 inhibitors and GLP-1 agonist. Furthermore, a significantly lower hazard ratio of cardiovascular mortality was found in both SGLT-2 inhibitors and GLP-1 agonists. Conclusion Comparing across all antidiabetic agents apart from insulin, SGLT-2 inhibitors provided extensively renoprotective effects among diabetic patients as well as reduced hazard ratios of heart failure, cardiovascular mortality, and all-cause mortality. GLP-1 agonists yielded benefits regarding progression of albuminuria, composite renal outcome, and cardiovascular and all-cause mortalities. DPP-4 inhibitors offered only renal protection including progression and regression of albuminuria. Keywords Antidiabetic agents · SGLT-2 inhibitors · GLP-1 agonists · DPP-4 inhibitors · Renal outcomes · Cardiovascular outcomes
Introduction
A portion of this work was presented as poster in the ASN annual meeting during November 5–10, 2019 in Washington DC, USA. * Paweena Susantitaphong [email protected] 1
2
Division of Nephrology, Department of Medicine, Faculty of Medicine, King Chulalongkorn Memorial Hospital, Chulalongkorn University, 1873 RAMA IV, Bangkok 10330, Thailand Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA, USA
Type 2 diabetes is one of the most prevalent chronic diseases affecting more than 500 million people worldwide [1]. Complications of type 2 diabetes include
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