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A series of large-scale randomized controlled trials (RCTs) demonstrated that SGLT2i use reduced the risk of kidney disease progression in patients with and without diabetes ( post hoc analysis of SUSTAIN6 and PIONEER6 demonstrated that semaglutide slowed the eGFR decline in T2D patients with a high risk of CVD ( With combination therapy of SGLT2i and GLP1Ra, the preceding drug did not affect the renal outcome in the main analysis of RECAP study ( post hoc analysis, the SGLT2i-preceding group had a slower rate of eGFR decline in comparison to the GLP1Ra-preceding group, and multiple regression analysis identified the preceding of SGLT2i as an independent and significant factor of change in eGFR decline

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These findings indicate that, at certain exposure levels, these metabolites have the potential to disrupt endocrine homeostasis and increase the risk of reproductive or developmental toxicity