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.
Keywords: 24-h urinary albumin; Albumin creatinine ratio; Canagliflozin; Composite renal outcome; Dapagliflozin; Empagliflozin; Ertugliflozin; Ipragliflozin remogliflozin; MAKE; Sotagliflozin; eGFR.
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