Comparative effectiveness of combining antidiabetic medications to treat renal impairment in patients with type 2 diabetes mellitus

Abstract The comparative renoprotective effects of metformin-GLP-1 RA (glucagon-like peptide 1 receptor agonist), metformin-DPP-4i (dipeptidyl peptidase 4 inhibitor) and metformin-oADM (other antidiabetes medication) in patients with DKD (diabetic kidney disease) were evaluated by assessing the asso...

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Main Authors: Qiu Mo, Terrence J. Adam, Steven G. Johnson, Amir Moheet, David S. Pieczkiewicz
Format: Article
Language:English
Published: Nature Portfolio 2025-07-01
Series:Scientific Reports
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Online Access:https://doi.org/10.1038/s41598-025-10299-1
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author Qiu Mo
Terrence J. Adam
Steven G. Johnson
Amir Moheet
David S. Pieczkiewicz
author_facet Qiu Mo
Terrence J. Adam
Steven G. Johnson
Amir Moheet
David S. Pieczkiewicz
author_sort Qiu Mo
collection DOAJ
description Abstract The comparative renoprotective effects of metformin-GLP-1 RA (glucagon-like peptide 1 receptor agonist), metformin-DPP-4i (dipeptidyl peptidase 4 inhibitor) and metformin-oADM (other antidiabetes medication) in patients with DKD (diabetic kidney disease) were evaluated by assessing the associations between renal impairment and combination therapies. Patients initially diagnosed with DKD between January 1, 2010, and January 1, 2017, were included. Those receiving combination treatment with metformin-GLP-1 RA, metformin-DPP-4i, or metformin-oADM were selected and paired. A logistic regression model was applied to generate odds ratios with 95% confidence intervals to assess the associations between the composite renal impairment outcomes and the combination ADM (antidiabetes medication) groups. Sensitivity analyses were also performed. Renal impairment was significantly reduced in patients who were treated with metformin-GLP-1 RA than in those treated with metformin-DPP-4i in the primary and secondary analyses (OR 0.60, P < 0.05 for the primary outcome; OR 0.44, P < 0.05 for the secondary outcome). The associations of renal impairment risk and ADM combination therapies with metformin-DPP-4i versus metformin-oADM were not statistically significant in either the primary or secondary analysis (OR = 1.22, P = 0.20 for the primary outcome; OR = 0.90, P = 0.53 for the secondary outcome). The results of the sensitivity analyses were consistent with those of the main analysis. The combination metformin-GLP-1 RA was associated with fewer renal impairment events compared to metformin-DPP-4i and metformin-oADM, indicating potential additive or synergistic effects within the combination metformin-GLP-1 RA group. Metformin-DPP-4i did not significantly improve renal impairment outcomes in this study.
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spelling doaj-art-08a19a8df88d448597cb599e5c5bdb1f2025-08-20T04:01:51ZengNature PortfolioScientific Reports2045-23222025-07-0115111210.1038/s41598-025-10299-1Comparative effectiveness of combining antidiabetic medications to treat renal impairment in patients with type 2 diabetes mellitusQiu Mo0Terrence J. Adam1Steven G. Johnson2Amir Moheet3David S. Pieczkiewicz4Institute for Health Informatics, University of MinnesotaInstitute for Health Informatics, University of MinnesotaInstitute for Health Informatics, University of MinnesotaDivision of Diabetes and Endocrinology, Department of Medicine, University of MinnesotaInstitute for Health Informatics, University of MinnesotaAbstract The comparative renoprotective effects of metformin-GLP-1 RA (glucagon-like peptide 1 receptor agonist), metformin-DPP-4i (dipeptidyl peptidase 4 inhibitor) and metformin-oADM (other antidiabetes medication) in patients with DKD (diabetic kidney disease) were evaluated by assessing the associations between renal impairment and combination therapies. Patients initially diagnosed with DKD between January 1, 2010, and January 1, 2017, were included. Those receiving combination treatment with metformin-GLP-1 RA, metformin-DPP-4i, or metformin-oADM were selected and paired. A logistic regression model was applied to generate odds ratios with 95% confidence intervals to assess the associations between the composite renal impairment outcomes and the combination ADM (antidiabetes medication) groups. Sensitivity analyses were also performed. Renal impairment was significantly reduced in patients who were treated with metformin-GLP-1 RA than in those treated with metformin-DPP-4i in the primary and secondary analyses (OR 0.60, P < 0.05 for the primary outcome; OR 0.44, P < 0.05 for the secondary outcome). The associations of renal impairment risk and ADM combination therapies with metformin-DPP-4i versus metformin-oADM were not statistically significant in either the primary or secondary analysis (OR = 1.22, P = 0.20 for the primary outcome; OR = 0.90, P = 0.53 for the secondary outcome). The results of the sensitivity analyses were consistent with those of the main analysis. The combination metformin-GLP-1 RA was associated with fewer renal impairment events compared to metformin-DPP-4i and metformin-oADM, indicating potential additive or synergistic effects within the combination metformin-GLP-1 RA group. Metformin-DPP-4i did not significantly improve renal impairment outcomes in this study.https://doi.org/10.1038/s41598-025-10299-1Type 2 diabetes mellitusDiabetic kidney diseaseAntidiabetic medicationsLogistic regression modelOdds ratioPropensity score matching
spellingShingle Qiu Mo
Terrence J. Adam
Steven G. Johnson
Amir Moheet
David S. Pieczkiewicz
Comparative effectiveness of combining antidiabetic medications to treat renal impairment in patients with type 2 diabetes mellitus
Scientific Reports
Type 2 diabetes mellitus
Diabetic kidney disease
Antidiabetic medications
Logistic regression model
Odds ratio
Propensity score matching
title Comparative effectiveness of combining antidiabetic medications to treat renal impairment in patients with type 2 diabetes mellitus
title_full Comparative effectiveness of combining antidiabetic medications to treat renal impairment in patients with type 2 diabetes mellitus
title_fullStr Comparative effectiveness of combining antidiabetic medications to treat renal impairment in patients with type 2 diabetes mellitus
title_full_unstemmed Comparative effectiveness of combining antidiabetic medications to treat renal impairment in patients with type 2 diabetes mellitus
title_short Comparative effectiveness of combining antidiabetic medications to treat renal impairment in patients with type 2 diabetes mellitus
title_sort comparative effectiveness of combining antidiabetic medications to treat renal impairment in patients with type 2 diabetes mellitus
topic Type 2 diabetes mellitus
Diabetic kidney disease
Antidiabetic medications
Logistic regression model
Odds ratio
Propensity score matching
url https://doi.org/10.1038/s41598-025-10299-1
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