TY - JOUR
T1 - 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
AU - van Ruiten, Charlotte C.
AU - van der Aart-van der Beek, Annemarie B.
AU - IJzerman, Richard G.
AU - Nieuwdorp, Max
AU - Hoogenberg, Klaas
AU - van Raalte, Daniël H.
AU - Heerspink, Hiddo J. L.
N1 - Funding Information: C.C.v.R. and A.B.v.d.A.v.d.B. have nothing to disclose. R.G.I.J. is principal investigator of studies sponsored by research grants from AstraZeneca, Eli Lilly & Co., and Novo Nordisk. M.N. serves on the Scientific Advisory Board of Caelus Pharmaceuticals, the Netherlands, and Kaleido, United States. R.G.I. and M.N. have reported that they received no personal payments in connection with the above‐mentioned activities, but all payments were directly transferred to the nonprofit Amsterdam UMC. No other potential conflicts of interest relevant to this article were reported. K.H. has consulting relationships with Novo Nordisk and Sanofi, and receives research operating funding from Novo Nordisk. D.H.v.R. has consulting relationships with Boehringer Ingelheim, Eli Lilly, Merck and Sanofi, and receives research operating funding from AstraZeneca, Boehringer Ingelheim‐Eli Lilly Diabetes Alliance and MSD. H.J.L.H. has consulting relationships with AbbVie, AstraZeneca, Bayer, Boehringer Ingelheim, CSL Pharma, Chinook, Dimerix, Gilead, Janssen, Merck, Mitsubishi Tanabe, Mundi Pharma, NovoNordisk, and Travere. Funding Information: The authors thank Ton Schweigmann of the Department of Radiology and Nuclear Medicine, and Ren?e de Meijer, Jeanette Boerop and Ingrid Knuffman of the Department of Internal Medicine for their assistance during the test visits, as well as the subjects who participated in this study. Publisher Copyright: © 2021 The Authors. Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd. Copyright: Copyright 2021 Elsevier B.V., All rights reserved.
PY - 2021/8
Y1 - 2021/8
N2 - Aims: To evaluate the effects of separate and combined use of the sodium-glucose cotransporter-2 (SGLT2) inhibitor dapagliflozin and the glucagon-like peptide-1 receptor agonist (GLP-1RA) exenatide on measures 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 (GFR) and kidney injury molecule-1:creatinine ratio (KIM-1:Cr). Results: At week 16, the mean UACR change from baseline was −39.6% (95% confidence interval [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 participants who were using angiotensin-converting enzyme inhibitors or angiotensin receptor blockers at baseline. Compared to placebo, in the exenatide-dapagliflozin group, an acute dip in estimated GFR was observed with creatinine-estimated GFR (−4.0 mL/min/1.73 m 2 [95% CI −9.3, 1.2]; P = 0.129) and cystatin C-estimated GFR (−10.4 mL/min/1.73 m 2 [95% CI −14.9, −5.8]; P < 0.001). The mean KIM-1:Cr difference in the combined treatment arm versus placebo was −43.8% (95% CI −73.5, 18.9; P = 0.129). 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.
AB - Aims: To evaluate the effects of separate and combined use of the sodium-glucose cotransporter-2 (SGLT2) inhibitor dapagliflozin and the glucagon-like peptide-1 receptor agonist (GLP-1RA) exenatide on measures 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 (GFR) and kidney injury molecule-1:creatinine ratio (KIM-1:Cr). Results: At week 16, the mean UACR change from baseline was −39.6% (95% confidence interval [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 participants who were using angiotensin-converting enzyme inhibitors or angiotensin receptor blockers at baseline. Compared to placebo, in the exenatide-dapagliflozin group, an acute dip in estimated GFR was observed with creatinine-estimated GFR (−4.0 mL/min/1.73 m 2 [95% CI −9.3, 1.2]; P = 0.129) and cystatin C-estimated GFR (−10.4 mL/min/1.73 m 2 [95% CI −14.9, −5.8]; P < 0.001). The mean KIM-1:Cr difference in the combined treatment arm versus placebo was −43.8% (95% CI −73.5, 18.9; P = 0.129). 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.
KW - GLP-1RA
KW - SGLT2 inhibitors
KW - dapagliflozin
KW - diabetic kidney disease
KW - exenatide
KW - glucagon-like peptide-1 receptor agonists
UR - http://www.scopus.com/inward/record.url?scp=85105754317&partnerID=8YFLogxK
U2 - https://doi.org/10.1111/dom.14410
DO - https://doi.org/10.1111/dom.14410
M3 - Article
C2 - 33908691
SN - 1462-8902
VL - 23
SP - 1851
EP - 1858
JO - Diabetes, Obesity and Metabolism
JF - Diabetes, Obesity and Metabolism
IS - 8
ER -