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Pleiotropic effects of antidiabetic agents on renal and cardiovascular outcomes: a meta-analysis of randomized controlled trials

International Urology and Nephrology volume 52, pages 1733–1745 (2020)Cite this article

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.

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Funding

This study was funded by a Grant from Research Unit for Metabolic Bone Disease in CKD patients. Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand.

Author information

Affiliations

  1. Division of Nephrology, Department of Medicine, Faculty of Medicine, King Chulalongkorn Memorial Hospital, Chulalongkorn University, 1873 RAMA IV, Bangkok, 10330, Thailand

    Api Chewcharat, Kullaya Takkavatakarn, Suramath Isaranuwatchai, Pisut Katavetin, Kearkiat Praditpornsilpa, Somchai Eiam-ong & Paweena Susantitaphong

  2. Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA, USA

    Api Chewcharat

  3. Division of Nephrology, Department of Medicine, Chulabhorn Hospital, HRH Princess Chulabhorn College of Medical Science, Chulabhorn Royal Academy, Bangkok, Thailand

    Suramath Isaranuwatchai

  4. Research Unit for Metabolic Bone Disease in CKD Patients, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand

    Paweena Susantitaphong

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  1. Api Chewcharat
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  2. Kullaya Takkavatakarn
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  4. Pisut Katavetin
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Contributions

Study design: AC and KT. Review of citations and articles: AC, KT, and SI. Analysis: PS. Manuscript preparation: AC, KT, and SI. Manuscript review and edits: AC, KT, SI, PS, KP, and SE.

Corresponding author

Correspondence to Paweena Susantitaphong.

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On behalf of all authors, Paweena Susantitaphong states that there is no conflict of interest.

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Chewcharat, A., Takkavatakarn, K., Isaranuwatchai, S. et al. Pleiotropic effects of antidiabetic agents on renal and cardiovascular outcomes: a meta-analysis of randomized controlled trials. Int Urol Nephrol 52, 1733–1745 (2020). https://doi.org/10.1007/s11255-020-02520-z

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  • DOI: https://doi.org/10.1007/s11255-020-02520-z

Keywords

  • Antidiabetic agents
  • SGLT-2 inhibitors
  • GLP-1 agonists
  • DPP-4 inhibitors
  • Renal outcomes
  • Cardiovascular outcomes