Evidence map›Paper›PMID 40207988›Full record

Trial reportPhysiological reports2025

Mechanistic evaluation of ertugliflozin in patients with type 2 diabetes and heart failure.

Yuliya Lytvyn, Rosalie A Scholtes, Eva M Boorsma, Vikas S Sridhar, Luxcia Kugathasan, Hongyan Liu, Leif E Lovblom, Louis Handoko, Charlotte M Mosterd, John S Floras and 6 more

Abstract readRandomized Controlled TrialMulticenter Study
PubMed Full text at PMC Publisher
In one paragraph

Trial report in Physiological reports, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
6citing papers in PubMed, 2 pooled it
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

6 citing papers in PubMed, 2 syntheses or guidelines pooled it.

  1. Pooled it
  2. Pooled it
  3. Trial
  4. Review
  5. Review
  6. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

16 authors.

Yuliya LytvynDivision of Nephrology, Department of Medicine, University Health Network, Toronto, Ontario, Canada.
Rosalie A ScholtesDepartment of Internal Medicine, Diabetes Center, Amsterdam UMC, Amsterdam, The Netherlands.
Eva M BoorsmaDepartment of Clinical Pharmacy and Pharmacology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
Vikas S SridharDivision of Nephrology, Department of Medicine, University Health Network, Toronto, Ontario, Canada.
Luxcia KugathasanDivision of Nephrology, Department of Medicine, University Health Network, Toronto, Ontario, Canada.ORCID 0000-0002-1802-9253
Hongyan LiuDivision of Nephrology, Department of Medicine, University Health Network, Toronto, Ontario, Canada.
Leif E LovblomBiostatistics Department, University Health Network, Toronto, Ontario, Canada.
Louis HandokoDepartment of Internal Medicine, Diabetes Center, Amsterdam UMC, Amsterdam, The Netherlands.
Charlotte M MosterdDepartment of Internal Medicine, Diabetes Center, Amsterdam UMC, Amsterdam, The Netherlands.
John S FlorasTemerty Faculty of Medicine, University of Toronto, Toronto, Ontario, Canada.
Kevin BurnsKidney Research Centre, The Ottawa Hospital, University of Ottawa, Ottawa, Ontario, Canada.
Tosin OsuntokunDivision of Cardiology, University Health Network, Toronto, Ontario, Canada.
Adriaan VoorsDepartment of Clinical Pharmacy and Pharmacology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
Daniel H van RaalteDepartment of Internal Medicine, Diabetes Center, Amsterdam UMC, Amsterdam, The Netherlands.
Hiddo J L HeerspinkDepartment of Clinical Pharmacy and Pharmacology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
David Z I CherneyDivision of Nephrology, Department of Medicine, University Health Network, Toronto, Ontario, Canada.

Funding

Merck Canada (Merck Canada Inc.)
6 · The paper itself

Abstract

The effect of sodium-glucose cotransporter-2 (SGLT2) inhibitor ertugliflozin on fluid volume and kidney function was assessed in patients with type 2 diabetes and heart failure. Thirty-four participants were randomized in this double-blind, placebo-controlled, parallel-group, multicenter study. Physiologic measurements were obtained under clamped euglycemia at baseline, 1 week, and 12 weeks of treatment. The primary outcome was the proximal tubular natriuretic effect of ertugliflozin versus placebo, measured by fractional excretion of lithium (FELi). Ertugliflozin did not increase FELi or total FENa at 1 week or 12 weeks. Ertugliflozin increased both mean 24-h urinary sodium excretion (47.5 ± 22.1 mmol/day vs. placebo, p = 0.032) and urinary volume (p = 0.009) at 1 week, which was attenuated at Week 12. Reductions in extracellular fluid (-1.9 ± 0.8 L, p = 0.01), estimated plasma volume (-11.9 ± 13.9%, p = 0.02), and supine mean arterial pressure (-6.6 ± 2.7 mmHg, p = 0.02) were significant at Week 12. Compared to placebo, ertugliflozin acutely increased circulating angiotensinogen and angiotensin-converting enzyme (ACE) levels, as well as urine adenosine and ACE2 activity (p < 0.05). Changes in other neurohormones, sympathetic activity, kidney, and systemic hemodynamics did not differ compared to placebo. Our findings suggest that SGLT2 inhibition shifts systemic volume toward a state of euvolemia, potentially lowering the risk of worsening heart failure.

Indexed as

Bridged Bicyclo Compounds, HeterocyclicDiabetes Mellitus, Type 2Heart FailureSodium-Glucose Transporter 2 InhibitorsAgedDouble-Blind MethodFemaleHumansMaleMiddle AgedBridged Bicyclo Compounds, HeterocyclicertugliflozinSodium-Glucose Transporter 2 Inhibitorsertugliflozinheart failureSGLT2 inhibitiontype 2 diabetes

Identifiers

PMID40207988
PMCPMC11983784

What OpenQuestion holds

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LicenceCC BY
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.