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Dose-dependent renoprotection efficacy of sglt2 inhibitors in type 2 diabetes: systematic review and network meta-analysis

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Abstract

Aim

To compare the relative effects of different dosages of sodium-glucose cotransport inhibitors (SGLT2i) for renoprotection in Type 2 diabetes mellitus.

Methods

The study searched different databases (PubMed, Embase, Scopus, and Web of Science) for studies comparing dose-dependent renoprotective efficacy defined as a decline in eGFR with the different “-flozins namely Empagliflozin, Canagliflozin, Dapagliflozin, Ertugliflozin, Ipragliflozin, Luseogliflozin, Remogliflozin and Sotagliflozin. The studies were compared with the Bayesian approach of network meta-analysis coupled with the random-effect model using the Cochrane risk of bias tool (RoB 2.0), and the surface under the cumulative ranking curve (SUCRA) score was allotted to each dosage of different SGLT-2i.

Results

A total of 43,434 citations were identified, out of which forty-five randomized trials with 48,067 patients, mentioning the flozin dose and eGFR as an endpoint, were found to be eligible for further analysis. The median duration of the follow-up in the trials was 12 months (IQR 5.5–16 months). Canagliflozin 100 mg demonstrated distinct eGFR benefit with an odds ratio of 2.3 (CI 0.72–3.9) compared to placebo. A statistically non-significant eGFR benefit was observed with all other “-flozins.” Canagliflozin 100 mg drug dose category showed the highest sucra rank probability score of 93%, followed by the Canagliflozin 300 mg and Dapagliflozin 5 mg with sucra rank probability scores of 69% and 65%, respectively. The Flozin-dose assessment against eGFR was similar to the albumin-creatinine ratios as the secondary endpoint in the SUCRA ranking.

Conclusion

The renoprotective efficacy of SGLT2i is independent of the incremental doses suggesting lower doses may suffice for renal outcomes.

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    Authors and Affiliations

    1. Department of Pharmacology, Postgraduate Institute of Medical Education and Research, Chandigarh, India

      Naveen C. Hegde, Ankit Kumar, Amol N. Patil, Samiksha Bhattacharjee, Nanda Gamad & Kripa Shanker Kasudhan

    2. Department of Nephrology, Postgraduate Institute of Medical Education and Research, Chandigarh, India

      Vivek Kumar

    3. Department of Endocrinology, Postgraduate Institute of Medical Education and Research, Chandigarh, 160012, India

      Ashu Rastogi

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    Contributions

    AR and ANP contributed equally to study selection, manuscript writing, review and approval to the manuscript, data extraction and manuscript writing and important intellectual content. SB and NG contributed to data analysis. NH, AK, KSK contributed to the literature search and study selection; data analysis. ANP and NG contributed to risk of bias, manuscript writing and important intellectual content. AR helped in conception, data check, important intellectual content, literature review and final approval.

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    Correspondence to Ashu Rastogi.

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    The present article is a systematic review of prior studies, hence informed consent and human, animal rights disclosure is not required.

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    Naveen C Hegde and Ankit Kumar are co-first authors.

    This article belongs to the topical collection diabetic nephropathy, managed by Giuseppe Pugliese.

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    Hegde, N.C., Kumar, A., Patil, A.N. et al. Dose-dependent renoprotection efficacy of sglt2 inhibitors in type 2 diabetes: systematic review and network meta-analysis. Acta Diabetol 60, 1311–1331 (2023). https://doi.org/10.1007/s00592-023-02126-8

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