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Renal, cardiovascular, and safety outcomes of adding sodium–glucose cotransporter-2 inhibitors to insulin therapy in patients with type-2 diabetes: a meta-analysis

  • Nephrology - Review
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Abstract

Aims

To investigate the renal, cardiovascular, and safety outcomes when sodium–glucose cotransporter-2 inhibitors (SGLT2is) were added to insulin therapy in patients with type-2 diabetes mellitus (T2DM).

Materials and methods

We searched Embase, PubMed, and Cochrane libraries for reports published up to Feb 2023. Randomized controlled trials (RCTs) comparing SGLT2is and insulin combination therapy (SGLT2is + INS group) with insulin therapy alone (INS group) in T2DM were included.

Results

Fourteen RCTs involving six thousand one hundred twenty subjects with durations of 12–104 weeks were included. Compared with the insulin group, the SGLT2is + INS group showed decreased glycosylated hemoglobin values and insulin dosages (P < 0.00001). Meanwhile, the SGLT2is + INS group had a reduced urinary albumin/creatinine ratio (UACR) by 25.42 mg/g and uric acid concentration (P = 0.030; P = 0.001, respectively) but the estimated glomerular filtration rate (eGFR) and renal-related adverse events were unaffected (P = 0.070; P = 0.880, respectively). Blood pressure and body weight were lower in the SGLT2is + INS group (P < 0.01). However, the risk of genital infection was bigger when SGLT2is were added to insulin therapy (P < 0.00001), but the risks of severe hypoglycemia or urinary tract infection were equal between the two groups (P > 0.05).

Conclusion

Adding SGLT2is to insulin therapy in T2DM patients showed better glucose control and decreased albuminuria, uric acid, blood pressure, and body weight without a reduction in the eGFR.

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Data availability

The authors confirm that the data supporting the findings of this study are available within the article or its supplementary materials.

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Acknowledgements

This study was supported by the Six Talent Peaks Project in Jiangsu Province (WSN-336); the Scientific Research Project of Health Commission in Jiangsu Province (LGY2020067); and the Scientific Research Project, Taizhou School of Clinical Medicine, Nanjing Medical University (TZKY20220110).

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  1. Qian Zhang and Qingqing Zhang contributed equally to this work and should be considered as co-first authors.

Authors and Affiliations

  1. Department of Endocrinology, The Affiliated Taizhou People’s Hospital of Nanjing Medical University, Taizhou School of Clinical Medicine, Nanjing Medical University, 366 Taihu Road, Taizhou, 225300, China

    Qian Zhang, Qingqing Zhang, Liu Yang, Shufang Yang & Yu Lu

  2. Graduate School of Dalian Medical University, Dalian, 116044, Liaoning, China

    Liu Yang

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Zhang, Q., Zhang, Q., Yang, L. et al. Renal, cardiovascular, and safety outcomes of adding sodium–glucose cotransporter-2 inhibitors to insulin therapy in patients with type-2 diabetes: a meta-analysis. Int Urol Nephrol 56, 557–570 (2024). https://doi.org/10.1007/s11255-023-03719-6

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