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Baseline eGFR, albuminuria and renal outcomes in patients with SGLT2 inhibitor treatment: an updated meta-analysis

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Abstract

Aims

To elucidate the association between baseline renal characteristics and the disparities in renal outcomes among patients with SGLT2i treatment.

Methods

Pubmed, Medline, Embase, the Cochrane Central Register of Controlled Trials and Clinicaltrial.gov were searched from inception to November 2022. Event-driven randomized controlled trials of SGLT2i with reports of renal outcomes were included. Sensitivity analyses of prespecified eGFR and UACR subgroups were conducted.

Results

Generally, compared with placebo, the use of SGLT2i was associated with improved renal prognosis (HR = 0.64, 95%CI 0.59–0.70). The magnitude of risk reductions in composite renal outcomes between SGLT2i versus placebo was comparable among different eGFR stratifications (normal renal function: HR = 0.49, 95%CI 0.31–0.79; mild renal impairment: HR = 0.57, 95%CI 0.48–0.68; moderate renal impairment: HR = 0.70, 95%CI 0.63–0.78; severe renal impairment: HR = 0.72, 95%CI 0.62–0.84; P for subgroup difference = 0.09). However, renal benefits seemd to be more prominent in normal to mildly increased albuminuria stratum (HR = 0.51, 95%CI 0.39–0.66) and severely increased albuminuria stratum (HR = 0.57, 95%CI 0.47–0.68), when compared with moderately increased albuminuria stratum (HR = 0.79, 95%CI 0.65–0.96; P for subgroup difference = 0.01).

Conclusions

Generally, the use of SGLT2i was consistently associated with decreased risk of renal events in all prespecified eGFR and albuminuria spectrums, even in patients with substantial renal impairment. The renal benefits of SGLT2i seemed to be independent of baseline eGFR, while the risk reduction in renal events was more profound among patients with mildly increased albuminuria or severely increased albuminuria.

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Data availability statement

All data relevant to the study are included in the article or uploaded as supplementary information. No more additional data are available.

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Acknowledgements

We thank the doctors, nurses and technicians for their practical during the study at Department of Endocrinology and Metabolism in Peking University People’s Hospital.

Funding

This work was supported by Beijing Natural Science Foundation (No. 7202216) and National Natural Science Foundation of China (No. 81970698 and No. 81970708). The funding agencies had no roles in the study design, data collection or analysis, decision to publish or preparation of the manuscript.

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Author notes

  1. Yunke Ma and Chu Lin contributed equally to the manuscript.

Authors and Affiliations

  1. Department of Endocrinology and Metabolism, Peking University People’s Hospital, No. 11 Xizhimen South Street, Xicheng District, Beijing, 100044, China

    Yunke Ma, Chu Lin, Xiaoling Cai, Suiyuan Hu, Xingyun Zhu, Fang Lv, Wenjia Yang & Linong Ji

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  1. Yunke Ma
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Contributions

LJ and XC conceptualized this study and designed the systematic review protocol; YM and CL performed the study selection and data extraction; XZ and SH checked the data for accuracy; FL provided with consultation for disagreement; YM, CL and XC performed the statistical analyses; YM, CL and XC prepared the outlines and wrote the manuscript. All authors contributed to the critical revision of manuscript drafts.

Corresponding authors

Correspondence to Xiaoling Cai or Linong Ji.

Ethics declarations

Conflict of interest

LJ has received fees for lecture presentations and for consulting from AstraZeneca, Merck, Metabasis, MSD, Novartis, Eli Lilly, Roche, Sanofi-Aventis and Takeda. No other support from any organization for the submitted work other than that described above.

Ethical approval

Since it is a meta-analysis, ethical approval is not applicable.

Ethical Standard Statement

All procedures performed in this study involving human participants were in accordance with the ethical standards of the institutional and national research committee and with the 1964 Helsinki Declaration and its later amendments.

Informed consent disclosure

Since it was a meta-analysis of randomized controlled trials, the informed consents were obtained from the participants before the enrollments of the clinical trials. No further informed consents were required for this meta-analysis.

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This article belongs to the topical collection Diabetic Nephropathy, managed by Giuseppe Pugliese.

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Ma, Y., Lin, C., Cai, X. et al. Baseline eGFR, albuminuria and renal outcomes in patients with SGLT2 inhibitor treatment: an updated meta-analysis. Acta Diabetol 60, 435–445 (2023). https://doi.org/10.1007/s00592-022-02022-7

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  • DOI: https://doi.org/10.1007/s00592-022-02022-7

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