What is the clinical evidence from this study?

Study design: Cohort. Population: Type 2 diabetes mellitus and end-stage kidney disease on dialysis (n=3376). Intervention: Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) vs. Dipeptidyl peptidase-4 inhibitors (DPP-4i). Primary outcome: Major adverse cardiovascular events (MACE), a composite of acute myocardial infarction, cerebral infarction, nontraumatic intracranial hemorrhage, subsequent STEMI, NSTEMI, cardiac arrest, and death (HR 0.88, 95% CI 0.78-0.99, p=0.036).

What question did this study set out to answer?

To evaluate the association between glucagon-like peptide-1 receptor agonists (GLP-1 RAs) and cardiovascular outcomes, mortality, and clinical complications among patients with type 2 diabetes receiving dialysis.

June 11, 2026Clinical Kidney JournalOpen Access

Glucagon-Like Peptide-1 Receptor Agonists and Cardiovascular Outcomes in Dialysis Patients With Type 2 Diabetes: A Real-World Propensity Score–Matched Study

Q: What does this research mean for the field?

GLP-1 receptor agonists are associated with a reduced risk of major adverse cardiovascular events compared with DPP-4 inhibitors in dialysis patients with type 2 diabetes. Novelty: ClaimNovelty.INCREMENTAL. Consensus alignment: ConsensusAlignment.NEUTRAL.

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Key result

GLP-1 receptor agonists linked to ~12% lower MACE risk vs DPP-4 inhibitors in dialysis.

HR 0.88
95% CI 0.78-0.99
P=0.036
n=3,376

Why the study?

Patients with T2DM undergoing dialysis face very high cardiovascular and mortality risks, but evidence for effective therapies is limited and the benefits of GLP-1 RAs in this population remain unclear.

Does GLP-1 RA therapy reduce major adverse cardiovascular events in adults with type 2 diabetes on maintenance dialysis compared to DPP-4 inhibitors?

Key Points

To evaluate the association between glucagon-like peptide-1 receptor agonists (GLP-1 RAs) and cardiovascular outcomes, mortality, and clinical complications among patients with type 2 diabetes receiving dialysis.
Retrospective, propensity score–matched cohort study analyzing electronic health records from the TriNetX US Collaborative Network between 2013 and 2022, with follow-up evaluated up to 5 years.
Identified 1 688 matched pairs of new GLP-1 RA users and dipeptidyl peptidase-4 inhibitor (DPP-4i) users from an initial cohort of 1 942 GLP-1 RA and 4 645 DPP-4i recipients.
GLP-1 RA users experienced a significantly lower rate of primary major adverse cardiovascular events (MACE) compared with DPP-4i users (31.2% [526 events] vs 38.2% [645 events]; HR 0.88, 95% CI 0.78–0.99; log-rank P = .036).
GLP-1 RA treatment was associated with significant reductions in all-cause mortality (16.8% vs 22.5%; HR 0.84, 95% CI 0.72–0.99), acute myocardial infarction (12.6% vs 16.4%; HR 0.84, 95% CI 0.70–0.99), and heart failure (34.4% vs 40.4%; HR 0.87, 95% CI 0.78–0.98).
Significant reductions also occurred for sepsis (22.6% vs 29.6%; HR 0.81, 95% CI 0.71–0.92), hospitalizations (52.8% vs 59.8%; HR 0.86, 95% CI 0.79–0.95), and emergency visits (41.5% vs 49.3%; HR 0.84, 95% CI 0.76–0.93).

Study Design

Type

Cohort (n=3,376)

Multicenter

Yes

Structured PICO

Does GLP-1 RA therapy reduce major adverse cardiovascular events in adults with type 2 diabetes on maintenance dialysis compared to DPP-4 inhibitors?

Population

3,376 propensity score-matched adults with type 2 diabetes mellitus and end-stage kidney disease on maintenance dialysis, followed for up to 5 years.

Exposure

Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) as a class, new users

Comparator

Dipeptidyl peptidase-4 inhibitors (DPP-4i) as a class, new users, 1:1 propensity score-matched active comparator

Outcome

Major adverse cardiovascular events (MACE), a composite of acute myocardial infarction, cerebral infarction, nontraumatic intracranial hemorrhage, subsequent ST-elevation myocardial infarction (STEMI), non-ST-elevation myocardial infarction (NSTEMI), cardiac arrest, and death, assessed from 1 day to 5 years after the index eventcomposite

Main Result

Hazard Ratio: 0.88 (95% CI 0.78–0.99)

Absolute Event Rate: 31.2% vs 38.2%

p-value: p=0.036

In a real-world propensity-matched cohort of patients with type 2 diabetes on dialysis, new initiation of GLP-1 receptor agonists was associated with significantly reduced risks of MACE, all-cause mortality, and healthcare utilization compared to DPP-4 inhibitors.

Limitations

Observational design subject to residual confounding and indication bias.
Inability to definitively establish a temporal sequence between the diagnosis of T2DM and the initiation of dialysis to verify diabetic kidney disease as the primary etiology of ESKD.
Medication exposure was inferred from prescription records without confirmed adherence or capture of discontinuation/intolerance.
Lack of consistent availability for laboratory parameters such as HbA1c, lipid levels, and inflammatory markers.
Residual baseline imbalances remained in serum calcium, phosphate, hemoglobin, and albumin despite propensity matching.
Lack of granularity regarding specific dialysis-related confounders such as dialysis vintage, vascular access types, CRP levels, ESA dosages, and phosphate binder formulations.
TriNetX database lacks specific inflammatory markers or immune parameters, making immunomodulatory effects speculative
Specific causes of death are often indistinguishable in the database, introducing competing risks

Implication

May inform glucose-lowering therapy choice in dialysis T2D; extends observational data but leaves open need for RCTs before practice change.

Abstract

Aims Patients with type 2 diabetes mellitus (T2DM) undergoing dialysis have extremely high cardiovascular and mortality risks, yet evidence for effective therapies is limited. The benefits of glucagon-like peptide-1 receptor agonists (GLP-1 RAs) in this population remain unclear. Methods We conducted a retrospective, propensity score–matched cohort study using the TriNetX US Collaborative Network (2013–2022). Among 1 688 matched pairs of new GLP-1 RA and DPP-4i users, the primary outcome was major adverse cardiovascular events (MACE), with secondary outcomes of all-cause mortality, heart failure, sepsis, hospitalization, and emergency visits. Results GLP-1 RAs users experienced significantly lower risk of MACE compared with DPP-4i users (HR 0.88, 95% CI 0.78–0.99). GLP-1 RAs were also associated with reduced all-cause mortality (HR 0.84, 95% CI 0.72–0.99), myocardial infarction (HR 0.84, 95% CI 0.70–0.99), heart failure (HR 0.87, 95% CI 0.78–0.98), and sepsis (HR 0.81, 95% CI 0.71–0.92). Healthcare utilization outcomes as hospitalization and emergency visits were also reduced. Findings were consistent across sensitivity and subgroup analyses. Conclusions In this large real-world dialysis cohort, GLP-1 RAs were associated with improved cardiovascular outcomes, survival, infection risk, and healthcare utilization, supporting their potential role in T2DM patients receiving dialysis.

Discussion

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Published by Clinical Kidney Journal · CC BY-NC

Cite This Study

Chen et al. (2026) conducted a cohort in Type 2 diabetes mellitus and end-stage kidney disease on dialysis (n=3,376). Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) vs. Dipeptidyl peptidase-4 inhibitors (DPP-4i) was evaluated on Major adverse cardiovascular events (MACE), a composite of acute myocardial infarction, cerebral infarction, nontraumatic intracranial hemorrhage, subsequent STEMI, NSTEMI, cardiac arrest, and death (HR 0.88, 95% CI 0.78-0.99, p=0.036). GLP-1 receptor agonists were associated with a significantly lower risk of major adverse cardiovascular events compared with DPP-4 inhibitors in dialysis patients with type 2 diabetes (HR 0.88).

synapsesocial.com/papers/6a2a50b680c8f91e7f39d30e https://doi.org/10.1093/ckj/sfag188

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Implication

May inform glucose-lowering therapy choice in dialysis T2D; extends observational data but leaves open need for RCTs before practice change.

Glucagon-Like Peptide-1 Receptor Agonists and Cardiovascular Outcomes in Dialysis Patients With Type 2 Diabetes: A Real-World Propensity Score–Matched Study

Key Points

Study Design

Structured PICO

Main Result

Limitations

Implication

Abstract

Discussion

Figures from the paper

Cite This Study

Glucagon-Like Peptide-1 Receptor Agonists and Cardiovascular Outcomes in Dialysis Patients With Type 2 Diabetes: A Real-World Propensity Score–Matched Study

Key Points

Study Design

Structured PICO

Main Result

Limitations

Implication

Abstract

Discussion

Figures from the paper

Cite This Study

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