TY - JOUR
T1 - Combination Treatment for Management of Chronic Kidney Disease and Type 2 Diabetes
T2 - A Review and Practical Guidance
AU - Mohsen, Mai
AU - Yi, Tae Won
AU - Faruque, Labib
AU - Ke, Calvin
AU - Cafazzo, Joseph A
AU - Pham, Quynh
AU - Sridhar, Vikas S
AU - Levin, Adeera
AU - Abdel-Qadir, Husam
AU - Persson, Frederik
AU - Wanner, Christoph
AU - Juni, Peter
AU - Butler, Javed
AU - Marx, Nikolaus
AU - Cherney, David
AU - Odutayo, Ayodele
N1 - © The Author(s) 2026. Published by Oxford University Press on behalf of the Endocrine Society. All rights reserved. For commercial re-use, please contact [email protected] for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact [email protected]. See the journal About page for additional terms.
PY - 2026/4/13
Y1 - 2026/4/13
N2 - CONTEXT: Renin-angiotensin system inhibitors (RASi), sodium glucose cotransporter-2 inhibitors (SGLT2i), nonsteroidal mineralocorticoid receptor antagonists (nsMRA), and glucagon-like peptide-1 receptor agonists (GLP-1RA) are key components of guideline-directed medical treatments (GDMT) for chronic kidney disease (CKD) with type 2 diabetes (T2D). However, the combined use of these medications remains uncommon in clinical practice, in part, due to the absence of specific guidance on implementing combination treatment. Herein, we aim to 1) summarize the evidence supporting combination GDMT in CKD with T2D, 2) propose a practical algorithm to guide the accelerated implementation of quadruple treatment, and 3) discuss strategies to improve uptake of combination treatment.EVIDENCE ACQUISITION: We searched PubMed from inception to present for English-speaking studies using the search terms "renin-angiotensin system inhibitor", "sodium glucose cotransporter-2 inhibitor", "nonsteroidal mineralocorticoid receptor antagonist", "glucagon-like peptide-1 receptor agonist", and "diabetes". We focused on clinical guidelines, randomized controlled trials (RCTs), and if necessary, large observational studies.EVIDENCE SYNTHESIS: SGLT2i, nsMRA, and GLP-1RA confer early cardiovascular and kidney protection through independent mechanisms, allowing them to be combined. RCTs support use of each agent on top of "standard care" and multiple clinical guidelines endorse combination treatment. However, the optimal order and timing for medication initiation, and the approach to managing treatment-related side effects remain uncertain, thereby limiting uptake of combination treatment.CONCLUSIONS: Current evidence supports the use of combination GDMT in CKD with T2D. We propose a combination treatment algorithm that may combat clinical inertia and achieve greater cardiorenal risk reduction in high-risk patients with CKD and T2D.
AB - CONTEXT: Renin-angiotensin system inhibitors (RASi), sodium glucose cotransporter-2 inhibitors (SGLT2i), nonsteroidal mineralocorticoid receptor antagonists (nsMRA), and glucagon-like peptide-1 receptor agonists (GLP-1RA) are key components of guideline-directed medical treatments (GDMT) for chronic kidney disease (CKD) with type 2 diabetes (T2D). However, the combined use of these medications remains uncommon in clinical practice, in part, due to the absence of specific guidance on implementing combination treatment. Herein, we aim to 1) summarize the evidence supporting combination GDMT in CKD with T2D, 2) propose a practical algorithm to guide the accelerated implementation of quadruple treatment, and 3) discuss strategies to improve uptake of combination treatment.EVIDENCE ACQUISITION: We searched PubMed from inception to present for English-speaking studies using the search terms "renin-angiotensin system inhibitor", "sodium glucose cotransporter-2 inhibitor", "nonsteroidal mineralocorticoid receptor antagonist", "glucagon-like peptide-1 receptor agonist", and "diabetes". We focused on clinical guidelines, randomized controlled trials (RCTs), and if necessary, large observational studies.EVIDENCE SYNTHESIS: SGLT2i, nsMRA, and GLP-1RA confer early cardiovascular and kidney protection through independent mechanisms, allowing them to be combined. RCTs support use of each agent on top of "standard care" and multiple clinical guidelines endorse combination treatment. However, the optimal order and timing for medication initiation, and the approach to managing treatment-related side effects remain uncertain, thereby limiting uptake of combination treatment.CONCLUSIONS: Current evidence supports the use of combination GDMT in CKD with T2D. We propose a combination treatment algorithm that may combat clinical inertia and achieve greater cardiorenal risk reduction in high-risk patients with CKD and T2D.
U2 - 10.1210/clinem/dgag163
DO - 10.1210/clinem/dgag163
M3 - Review
C2 - 41973867
SN - 0021-972X
JO - The Journal of clinical endocrinology and metabolism
JF - The Journal of clinical endocrinology and metabolism
ER -