What is the clinical evidence from this study?

Study design: Cohort. Population: Type 2 Diabetes Mellitus and Chronic Kidney Disease (n=19139). Intervention: Triple therapy (RAASi, SGLT-2i, and GLP1-RA) vs. RAASi monotherapy. Primary outcome: all-cause mortality (aHR 0.317, 95% CI 0.234-0.429).

What does this research mean for the field?

Triple therapy with RAASi, SGLT-2i, and GLP1-RA significantly reduces all-cause mortality and major adverse kidney events compared to RAASi monotherapy in patients with type 2 diabetes and chronic kidney disease. Novelty: ClaimNovelty.INCREMENTAL. Consensus alignment: ConsensusAlignment.NEUTRAL.

What question did this study set out to answer?

To evaluate the comparative effectiveness and potential additive benefits of combining SGLT-2 inhibitors and GLP-1 receptor agonists with baseline RAAS inhibitor therapy in patients with type 2 diabetes and chronic kidney disease.

August 29, 2026Nephrology Dialysis Transplantation

Triple therapy with RAASi, SGLT-2i, and GLP1-RA linked to ~68% lower mortality versus RAASi alone.

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Why the study?

Does the addition of SGLT-2i, GLP1-RA, or their combination to RAASi therapy reduce mortality and adverse kidney events in patients with T2DM and CKD?

Population

19,139 patients with type 2 diabetes mellitus and chronic kidney disease with eGFR between 20-60 mL/min and…

Comparison

Addition of sodium glucose cotransporter 2… vs RAASi monotherapy.

Design

Cohort

Key result

Triple therapy with RAASi, SGLT-2i, and GLP1-RA reduced all-cause mortality compared to RAASi monotherapy (aHR 0.317; 95% CI 0.234-0.429).

Authors

JCJanis Casper JDJulian Doricic ZTZhejia Tian

Discussion

Member takes

Overview

May support additive cardiorenal benefits of SGLT2i plus GLP-1RA in T2DM-CKD; leaves open need for randomized outcome trials.

Key Points

To evaluate the comparative effectiveness and potential additive benefits of combining SGLT-2 inhibitors and GLP-1 receptor agonists with baseline RAAS inhibitor therapy in patients with type 2 diabetes and chronic kidney disease.
Target-trial emulation with propensity score matching using real-world data from the US Collaborative Network in TriNetX (N=19,139).
Included patients with type 2 diabetes, established RAAS inhibitor treatment, and eGFR between 20–60 mL/min in a first-user design.
Evaluated all-cause mortality as the primary outcome and major adverse kidney events (MAKE) and a composite of mortality and MAKE as secondary outcomes using Kaplan-Meier survival analysis.
Dual therapy significantly reduced all-cause mortality compared to RAAS inhibitor monotherapy for RAASi + SGLT-2i (aHR 0.602, 95% CI 0.528–0.686) and RAASi + GLP1-RA (aHR 0.597, 95% CI 0.507–0.702).
Triple therapy demonstrated the greatest reduction in all-cause mortality compared to RAAS inhibitor monotherapy (aHR 0.317, 95% CI 0.234–0.429).
Secondary outcomes also favored triple therapy, showing substantial risk reductions for MAKE (aHR 0.509, 95% CI 0.374–0.693) and the composite endpoint (aHR 0.414, 95% CI 0.328–0.524).

Study Design

Type

Cohort (n=19,139)

Multicenter

Yes

Structured PICO

Does the addition of SGLT-2i, GLP1-RA, or their combination to RAASi therapy reduce mortality and adverse kidney events in patients with T2DM and CKD?

Population

19,139 patients with type 2 diabetes, chronic kidney disease (eGFR 20-60 mL/min), and established RAASi treatment.

Exposure

Addition of sodium glucose cotransporter 2 inhibitors (SGLT-2i), glucagon-like peptide-1 receptor agonists (GLP1-RA), or both (triple therapy) to baseline RAASi treatment.

Comparator

RAASi monotherapy (evaluated using target-trial emulation with propensity score matching).

Outcome

All-cause mortalityhard clinical

Main Result

Hazard Ratio: 0.317 (95% CI 0.234–0.429)

In patients with T2DM and CKD, adding both an SGLT-2i and a GLP1-RA to baseline RAASi therapy is associated with a substantial reduction in all-cause mortality and major adverse kidney events compared to RAASi monotherapy.

Cite This Study

Casper et al. (2026) conducted a cohort in Type 2 Diabetes Mellitus and Chronic Kidney Disease (n=19,139). Triple therapy (RAASi, SGLT-2i, and GLP1-RA) vs. RAASi monotherapy was evaluated on all-cause mortality (aHR 0.317, 95% CI 0.234-0.429). Triple therapy with RAASi, SGLT-2i, and GLP1-RA reduced all-cause mortality compared to RAASi monotherapy (aHR 0.317; 95% CI 0.234-0.429).

synapsesocial.com/papers/6a92996e8e5d7d1fc0c11540 https://doi.org/10.1093/ndt/gfag198

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August 29, 2026Nephrology Dialysis Transplantation

Triple therapy with RAASi, SGLT-2i, and GLP1-RA linked to ~68% lower mortality versus RAASi alone.

View Full Paper

Ask AI

Bookmark

Why the study?

Does the addition of SGLT-2i, GLP1-RA, or their combination to RAASi therapy reduce mortality and adverse kidney events in patients with T2DM and CKD?

Population

19,139 patients with type 2 diabetes mellitus and chronic kidney disease with eGFR between 20-60 mL/min and…

Comparison

Addition of sodium glucose cotransporter 2… vs RAASi monotherapy.

Design

Cohort

Key result

Triple therapy with RAASi, SGLT-2i, and GLP1-RA reduced all-cause mortality compared to RAASi monotherapy (aHR 0.317; 95% CI 0.234-0.429).

Authors

JCJanis Casper JDJulian Doricic ZTZhejia Tian

Discussion

Member takes

Overview

May support additive cardiorenal benefits of SGLT2i plus GLP-1RA in T2DM-CKD; leaves open need for randomized outcome trials.

Key Points

To evaluate the comparative effectiveness and potential additive benefits of combining SGLT-2 inhibitors and GLP-1 receptor agonists with baseline RAAS inhibitor therapy in patients with type 2 diabetes and chronic kidney disease.
Target-trial emulation with propensity score matching using real-world data from the US Collaborative Network in TriNetX (N=19,139).
Included patients with type 2 diabetes, established RAAS inhibitor treatment, and eGFR between 20–60 mL/min in a first-user design.
Evaluated all-cause mortality as the primary outcome and major adverse kidney events (MAKE) and a composite of mortality and MAKE as secondary outcomes using Kaplan-Meier survival analysis.
Dual therapy significantly reduced all-cause mortality compared to RAAS inhibitor monotherapy for RAASi + SGLT-2i (aHR 0.602, 95% CI 0.528–0.686) and RAASi + GLP1-RA (aHR 0.597, 95% CI 0.507–0.702).
Triple therapy demonstrated the greatest reduction in all-cause mortality compared to RAAS inhibitor monotherapy (aHR 0.317, 95% CI 0.234–0.429).
Secondary outcomes also favored triple therapy, showing substantial risk reductions for MAKE (aHR 0.509, 95% CI 0.374–0.693) and the composite endpoint (aHR 0.414, 95% CI 0.328–0.524).

Study Design

Type

Cohort (n=19,139)

Multicenter

Yes

Structured PICO

Does the addition of SGLT-2i, GLP1-RA, or their combination to RAASi therapy reduce mortality and adverse kidney events in patients with T2DM and CKD?

Population

19,139 patients with type 2 diabetes, chronic kidney disease (eGFR 20-60 mL/min), and established RAASi treatment.

Exposure

Addition of sodium glucose cotransporter 2 inhibitors (SGLT-2i), glucagon-like peptide-1 receptor agonists (GLP1-RA), or both (triple therapy) to baseline RAASi treatment.

Comparator

RAASi monotherapy (evaluated using target-trial emulation with propensity score matching).

Outcome

All-cause mortalityhard clinical

Main Result

Hazard Ratio: 0.317 (95% CI 0.234–0.429)

Cite This Study

synapsesocial.com/papers/6a92996e8e5d7d1fc0c11540 https://doi.org/10.1093/ndt/gfag198

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