Effect of exenatide twice daily and dapagliflozin, alone and in combination, on markers of kidney function in obese patients with type 2 diabetes: A prespecified secondary analysis of a randomized controlled clinical trial.

Aims Sodium glucose co-transporter 2 inhibitors (SGLT2i) and glucagon-like peptide-1 receptor agonist (GLP-1 RA) slow progression of kidney function decline, possibly through complimentary yet distinct mechanisms of action, providing a rationale for combination therapy. However, there is limited data on the effects of the combined use of SGLT2i and GLP-1RA on parameters of kidney function. Methods In this prespecified secondary analysis of the DECREASE trial, we enrolled 66 obese patients with type 2 diabetes in a 16-week randomized-double-blind placebo-controlled clinical trial to investigate the effects of dapagliflozin and exenatide twice daily alone or in combination versus placebo on 24-hour urinary albumin:creatinine ratio (UACR), creatinine and cystatin C-estimated glomerular filtration rate (eGFR) and kidney injury molecule-1:creatinine ratio (KIM-1:Cr). Results At week 16, mean UACR change from baseline was -39.6% [95% CI -58.6%, -11.9%; p = 0.001] in the combined exenatide-dapagliflozin group; -18.1% [95% CI -43.1, 18.0; p = 0.278] in the dapagliflozin group; -15.6% [95% CI -41.4, 21.6; p = 0.357] in the exenatide group and - 11.0% [95% CI -39.8, 31.5; p = 0.552] in the placebo group. Compared to placebo, UACR difference at week 16 in the exenatide-dapagliflozin group was -32.2% [95% CI -60.7, 16.9; p = 0.159). Effects were similar in 37 patients who were using ACE-inhibitors or angiotensin receptor blockers at baseline. Compared to placebo, in the exenatide-dapagliflozin group, an acute dip in eGFR was observed with creatinine-estimated GFR (-4.0 mL/min/1.73m2 [95% CI -9.3, 1.2]; p = 0.129) and cystatin C-estimated GFR (-10.4 mL/min/1.73m2 [95% CI -14.9, -5.8]; p Conclusion This prespecified secondary analysis suggests that combined therapy with exenatide and dapagliflozin may have synergistic effects on markers of kidney function compared to either therapy alone or placebo in obese patients with type 2 diabetes. This article is protected by copyright. All rights reserved.