Volume 30, Issue 172, June 2026

Paradox of an early decline in estimated glomerular filtration rate during initiation of sodium-glucose cotransporter 2 inhibitors: A literature review of mechanisms, safety, clinical significance, and management strategies

Kinga Polityńska^1♦, Klaudia Samuła¹, Martyna Sarzyńska¹, Mateusz Szabat², Sylwia Lepak¹, Zuzanna Irzyk¹, Dominika Ruszel¹, Emilia Goc¹, Julia Rogała¹, Katarzyna Markuszka¹

¹Faculty of Medicine, Collegium Medicum, University of Rzeszów, Rzeszów, Poland
²Clinical Provincial Hospital No.2, Rzeszów, Poland

^♦Corresponding author
Kinga Polityńska, Faculty of Medicine, Collegium Medicum, University of Rzeszów, Rzeszów, Poland

ABSTRACT

Sodium-glucose cotransporter 2 inhibitors (SGLT2i) are a fundamental part of the therapeutic approach for patients with type 2 diabetes mellitus (T2DM), heart failure (HF), or chronic kidney disease (CKD), and the phenomena observed during their initiation are increasingly well understood. There is one such phenomenon, a transient decrease in estimated glomerular filtration rate (eGFR), known as the eGFR dip or initial eGFR decline. The eGFR dip, in medical understanding, has evolved from a potential adverse event to a positive pharmacodynamic marker (bioassay), reflecting the activation of a nephroprotective mechanism. This paper summarizes the mechanism, safety, management, and prognostic significance of this effect, based mainly on scientific articles searched in the PubMed database published in the past 10 years, with a particular focus on meta-analyses, randomized controlled trials (RCTs), post hoc analyses, real-world evidence (RWE), and retrospective observational studies. This dip, with the mean decrease of 3–5 ml/min/1.73 m², occurs in most patients within the first 2–4 weeks of SGLT2i initiation. The dip’s cause is fully reversible tubuloglomerular feedback (TGF) activation, unrelated to increased biomarkers of structural damage. Clinical guidelines actually promote a shift from reactive monitoring to “strategic tolerance”, accepting an eGFR dip up to 30% without interrupting treatment. Modern SGLT2i monitoring strategies require a combination with research aimed at personalizing recommendations for various groups to minimize unnecessary discontinuation and maximize the nephroprotective benefits of treatment.

Keywords: SGLT2 inhibitors, initial eGFR decline, eGFR dip, tubulogromerular feedback (TGF), cardionephroprotection

Medical Science, 2026, 30, e105ms3852

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Published: 18 June 2026