Abstract Aim To investigate the influence of sodium/glucose cotransporter‐2 inhibitors (SGLT‐2i) on renal function during the course of its administration, particularly in the initial weeks. Materials and Methods Randomized controlled trials (RCTs) related to SGLT‐2i were searched in databases (MEDLINE, EMBASE, and Cochrane Central Register) from the database's inception to August 31, 2021. All RCTs reported the kidney outcomes of SGLT2i versus active or placebo control were included, regardless of the presence of diabetes in the patients and the baseline estimated glomerular filtration rate (eGFR). The Cochrane Collaboration risk of bias tool was used to assess the quality of the included studies. All outcome comparisons were performed using the RevMan 5.4 software. Results Eleven RCTs with 58 534 participants reporting prespecified renal outcomes were identified. There was no heterogeneity in the baseline eGFR and urine albumin‐to‐creatinine ratio in the included studies. In the initial 2–4 weeks, there was an acute decline of eGFR in the SGLT‐2i group compared with placebo group (weighted mean difference [WMD] −3.35 ml/min/1.73 m2; 95% CI, −3.81 to −2.90; I2 = 35%, p = .15); When compared to baseline eGFR in the SGLT‐2i group, the WMD was −4.02 ml/min/1.73 m2 (95% confidence interval [CI], −3.61 to −4.44; I2 = 0%, p = .45). The renoprotective effect gradually appeared, and the decline rate of eGFR in the SGLT‐2i group was sustained slower than placebo. However, the statistically significant benefit of SGLT‐2i did not appear until the 104th week (the second year) (WMD 0.35 ml/min/1.73 m2, 95% CI, 0.04 to 0.66; I2 = 45%, p = .08). Subgroup analysis showed SGLT‐2i had a similar benefit on renal function regardless of baseline eGFR values. Conclusion SGLT‐2i consistently slowed the deterioration of eGFR since the early stage of administration, even in patients with chronic kidney disease. However, there was an acute decline in eGFR in the initial 2–4 weeks; afterwards the renoprotective effect of SGLT‐2i gradually appeared and remained stable in the next few years.
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