Renal haemodynamic response to sodium-glucose cotransporter-2 inhibition does not depend on protein intake: An analysis of three randomized controlled trials

Annemarie B. van der Aart-van der Beek, David Cherney, Gozewijn D. Laverman, Bergur Stefansson, Daniel H. van Raalte, Klaas Hoogenberg, Daniel Reyner, Qiang Li, Gian Luca di Tanna, Peter J. Greasley, Hiddo J. L. Heerspink*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review


High protein intake may increase intraglomerular pressure through dilation of the afferent arteriole. Sodium-glucose cotransporter-2 (SGLT2) inhibitors may reduce intraglomerular pressure through activation of tubuloglomerular feedback. Given these opposing effects, we assessed whether the effect of dapagliflozin on glomerular filtration rate (GFR) and urinary albumin-to-creatinine ratio (UACR) was modified by estimated dietary protein intake using data from three separate randomized controlled trials (DELIGHT, IMPROVE and DIAMOND). The median protein intake was 58.4, 63.6 and 90.0 g/d, respectively. In the DELIGHT trial (n = 233), dapagliflozin compared to placebo caused an acute and reversible dip in GFR of 2.1 and 2.2 mL/min/1.73 m2, and reduced UACR by 20.5% and 28.4% in participants with high and low protein intake, respectively. Similarly, in IMPROVE (n = 30) and DIAMOND (n = 53), the effect of dapagliflozin on GFR and UACR was comparable in participants with high and low protein intake (all P for interaction > 0.40). This post hoc, exploratory analysis of three clinical trials suggests that dietary protein intake does not modify the individual response of clinical kidney variables to dapagliflozin.
Original languageEnglish
Pages (from-to)1961-1967
Number of pages7
JournalDiabetes, Obesity and Metabolism
Issue number8
Early online date2021
Publication statusPublished - Aug 2021

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