Dulaglutide Slowed Kidney Function Decline by 25% in People with Type 2 Diabetes

In nearly 10,000 people with type 2 diabetes, weekly dulaglutide reduced kidney function decline by 25% compared to placebo — an effect that held regardless of starting kidney health.

Botros, Fady T et al.·Diabetes care·2023·Strong Evidencepost-hoc-analysis
RPEP-06755Post Hoc AnalysisStrong Evidence2023RETHINKTHC RESEARCH DATABASErethinkthc.com/research

Quick Facts

Study Type
post-hoc-analysis
Evidence
Strong Evidence
Sample
N=9,901
Participants
9,901 adults with type 2 diabetes who had previous cardiovascular disease or cardiovascular risk factors, from the REWIND trial

What This Study Found

Dulaglutide 1.5 mg reduced the risk of kidney function-related outcomes by 25% compared to placebo (HR 0.75, 95% CI 0.62–0.92, p = 0.004) in nearly 10,000 people with type 2 diabetes. Specifically, sustained ≥40% eGFR decline occurred 28% less frequently with dulaglutide (HR 0.72, p = 0.002).

The annual rate of kidney function decline was significantly slower with dulaglutide (-1.37 vs -1.56 mL/min/1.73 m²/year, p < 0.001). Importantly, the kidney-protective effect was consistent regardless of baseline kidney function or albumin levels — meaning it benefited patients across the spectrum of kidney health.

Key Numbers

n=9,901 (4,949 dulaglutide, 4,952 placebo) · HR 0.75 (95% CI 0.62–0.92, p = 0.004) for composite kidney outcome · HR 0.72 (p = 0.002) for ≥40% sustained eGFR decline · eGFR slope: -1.37 vs -1.56 mL/min/1.73 m²/year (p < 0.001) · consistent across UACR and eGFR subgroups

How They Did This

Post hoc analysis of the REWIND trial, a large randomized, placebo-controlled cardiovascular outcomes trial. Intent-to-treat analyses of 9,901 participants with type 2 diabetes examined kidney function endpoints (excluding macroalbuminuria) including sustained ≥40% eGFR decline, end-stage renal disease, and renal-related death. Subgroup analyses were conducted by baseline kidney function (eGFR) and albumin levels (UACR).

Why This Research Matters

Diabetic kidney disease is the leading cause of kidney failure worldwide, affecting roughly 40% of people with type 2 diabetes. This analysis is significant because it strips out the albuminuria component — which was the main driver of the original REWIND kidney results — and shows that dulaglutide genuinely slows the loss of kidney function itself. This matters because eGFR decline is a harder, more clinically meaningful endpoint than albuminuria alone.

The Bigger Picture

The GLP-1 drug class is rapidly accumulating evidence for organ protection beyond blood sugar and weight. REWIND showed cardiovascular benefits; this analysis adds kidney protection. Combined with similar kidney findings for semaglutide (FLOW trial) and liraglutide, there's now a compelling case that GLP-1 agonists as a class protect the kidneys in diabetes. This is reshaping treatment guidelines to prioritize GLP-1 drugs in patients with or at risk for diabetic kidney disease.

What This Study Doesn't Tell Us

Post hoc analysis — the kidney function outcomes were not the primary endpoint of the original REWIND trial, so these results are exploratory. The original trial was powered for cardiovascular events, not kidney endpoints. While the results are statistically significant and clinically meaningful, they require confirmation in a dedicated kidney outcomes trial. The subgroup analyses, while consistent, have limited statistical power individually.

Questions This Raises

  • ?Would a dedicated kidney outcomes trial with dulaglutide confirm these post hoc findings with even stronger evidence?
  • ?How does dulaglutide's kidney protection compare to semaglutide's FLOW trial results?
  • ?What's the mechanism — is the kidney benefit from better glucose control, weight loss, direct renal effects, or some combination?

Trust & Context

Key Stat:
HR 0.75 (25% risk reduction) Dulaglutide reduced the composite kidney function outcome — including sustained eGFR decline, end-stage kidney disease, and renal death — by 25% versus placebo in nearly 10,000 diabetic patients.
Evidence Grade:
Strong evidence: derived from the large, well-conducted REWIND randomized controlled trial (n=9,901). However, this is a post hoc analysis rather than a pre-specified primary endpoint, which reduces the strength slightly. The consistency across subgroups and multiple kidney metrics strengthens the findings.
Study Age:
Published in 2023 in Diabetes Care. These findings contribute to the growing evidence base for GLP-1 kidney protection, alongside the 2024 FLOW trial (semaglutide) which was the first dedicated kidney outcomes trial for a GLP-1 drug.
Original Title:
Dulaglutide and Kidney Function-Related Outcomes in Type 2 Diabetes: A REWIND Post Hoc Analysis.
Published In:
Diabetes care, 46(8), 1524-1530 (2023)
Database ID:
RPEP-06755

Evidence Hierarchy

Meta-Analysis / Systematic Review
Randomized Controlled Trial
Cohort / Case-Control
Cross-Sectional / ObservationalSnapshot without intervening
This study
Case Report / Animal Study
What do these levels mean? →

Frequently Asked Questions

Does dulaglutide actually protect the kidneys, or just improve albuminuria?

This study specifically addressed that question by removing the albuminuria component from the analysis. Even without counting improvements in albuminuria, dulaglutide still reduced the risk of hard kidney outcomes — sustained eGFR decline, kidney failure, and kidney-related death — by 25%. This suggests genuine kidney function protection beyond just improving a urine marker.

Do you need to already have kidney problems for dulaglutide to help?

No. The kidney protection was consistent regardless of baseline kidney function — patients with normal kidneys (eGFR ≥60) and those with existing impairment (eGFR <60) both benefited. This suggests dulaglutide may be protective at all stages, from prevention to slowing existing disease.

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Cite This Study

RPEP-06755·https://rethinkpeptides.com/research/RPEP-06755

APA

Botros, Fady T; Gerstein, Hertzel C; Malik, Raleigh; Nicolay, Claudia; Hoover, Anastasia; Turfanda, Ibrahim; Colhoun, Helen M; Shaw, Jonathan E. (2023). Dulaglutide and Kidney Function-Related Outcomes in Type 2 Diabetes: A REWIND Post Hoc Analysis.. Diabetes care, 46(8), 1524-1530. https://doi.org/10.2337/dc23-0231

MLA

Botros, Fady T, et al. "Dulaglutide and Kidney Function-Related Outcomes in Type 2 Diabetes: A REWIND Post Hoc Analysis.." Diabetes care, 2023. https://doi.org/10.2337/dc23-0231

RethinkPeptides

RethinkPeptides Research Database. "Dulaglutide and Kidney Function-Related Outcomes in Type 2 D..." RPEP-06755. Retrieved from https://rethinkpeptides.com/research/botros-2023-dulaglutide-and-kidney-functionrelated

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Study data sourced from PubMed, a service of the U.S. National Library of Medicine, National Institutes of Health.

This study breakdown was produced by the RethinkPeptides research team. We analyze and report published research findings without making health recommendations. All interpretations are based solely on the published abstract and study data.