Albuminuria-lowering effect of dapagliflozin, exenatide, and their combination in patients with type 2 diabetes: A randomized cross-over clinical study

Annemarie B. van der Aart-van der Beek, Ellen Apperloo, Niels Jongs, Dennis B. Rouw, C. David Sjöström, Iris Friedli, Lars Johansson, Daniël H. van Raalte, Klaas Hoogenberg, Hiddo J. L. Heerspink

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Aim: To evaluate the albuminuria-lowering effect of dapagliflozin, exenatide, and the combination of dapagliflozin and exenatide in patients with type 2 diabetes and microalbuminuria or macroalbuminuria. Methods: Participants with type 2 diabetes, an estimated glomerular filtration rate (eGFR) of more than 30 ml/min/1.73m2 and an urinary albumin: creatinine ratio (UACR) of more than 3.5 mg/mmol and 100 mg/mmol or less completed three 6-week treatment periods, during which dapagliflozin 10 mg/d, exenatide 2 mg/wk and both drugs combined were given in random order. The primary outcome was the percentage change in UACR. Secondary outcomes included blood pressure, HbA1c, body weight, extracellular volume, fractional lithium excretion and renal haemodynamic variables as determined by magnetic resonance imaging. Results: We enrolled 20 patients, who completed 53 treatment periods in total. Mean percentage change in UACR from baseline was –21.9% (95% CI: –34.8% to –6.4%) during dapagliflozin versus –7.7% (95% CI: –23.5% to 11.2%) during exenatide and –26.0% (95% CI: –38.4% to –11.0%) during dapagliflozin-exenatide treatment. No correlation was observed in albuminuria responses between the different treatments. Numerically greater reductions in systolic blood pressure, body weight and eGFR were observed during dapagliflozin-exenatide treatment compared with dapagliflozin or exenatide alone. Renal blood flow and effective renal plasma flow (ERPF) did not significantly change with either treatment regimen. However, all but four and two patients in the dapagliflozin and dapagliflozin-exenatide groups, respectively, showed reductions in ERPF. The filtration fraction did not change during treatment with dapagliflozin or exenatide, and decreased during dapagliflozin-exenatide treatment (–1.6% [95% CI: –3.2% to –0.01%]; P =.048). Conclusions: In participants with type 2 diabetes and albuminuria, treatment with dapagliflozin, exenatide and dapagliflozin-exenatide reduced albuminuria, with a numerically larger reduction in the combined dapagliflozin-exenatide treatment group.
Original languageEnglish
Pages (from-to)1758-1768
Number of pages11
JournalDiabetes, Obesity and Metabolism
Issue number6
Early online date2023
Publication statusPublished - Jun 2023


  • SGLT2
  • albuminuria
  • chronic kidney disease
  • dapagliflozin
  • exenatide

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