Evidence mapPaperPMID 41817689Full record

Trial reportDiabetologia2026

Impact of canagliflozin on the cardiorenal effects of dietary sodium intake in type 2 diabetes: a post hoc analysis of the CREDENCE trial.

Martina Chiriacò, Domenico Tricò, Alberto Giannoni, Luca Sacchetta, Lorenzo Nesti, Simona Baldi, Tiziana Scozzaro, Vincenzo Castiglione, Andrea Natali, Ele Ferrannini

Registry-linked trialAbstract readRandomized Controlled Trial
PubMed Publisher
In one paragraph

Trial report in Diabetologia, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It reports registered trial NCT02065791. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing papers in PubMed
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.

NCT02065791 phase3completed

A Randomized, Double-blind, Event-driven, Placebo-controlled, Multicenter Study of the Effects of Canagliflozin on Renal and Cardiovascular Outcomes in Subjects With Type 2 Diabetes Mellitus and Diabetic Nephropathy

Ran2014Enrolled4,401Registered outcomes8Posted comparisons8ConditionsDiabetes Mellitus, Type 2, Diabetic NephropathyArmsCanagliflozin, Placebo
Open the trial in the graph
3 · Its place in the literature

Who cites it

0 citing papers in PubMed.

No citing paper in PubMed yet.

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

10 authors.

Martina ChiriacòDepartment of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy. martina.chiriaco@med.unipi.it.ORCID http://orcid.org/0000-0003-0174-4549
Domenico TricòDepartment of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy.ORCID http://orcid.org/0000-0002-7633-1346
Alberto GiannoniHealth Science Interdisciplinary Center, Scuola Superiore Sant'Anna, Pisa, Italy.ORCID http://orcid.org/0000-0001-9314-2005
Luca SacchettaDepartment of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy.ORCID http://orcid.org/0000-0001-7005-1215
Lorenzo NestiDepartment of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy.ORCID http://orcid.org/0000-0002-0560-6496
Simona BaldiDepartment of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy.ORCID http://orcid.org/0000-0002-8296-4238
Tiziana ScozzaroDepartment of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy.ORCID http://orcid.org/0000-0001-8327-2295
Vincenzo CastiglioneHealth Science Interdisciplinary Center, Scuola Superiore Sant'Anna, Pisa, Italy.ORCID http://orcid.org/0000-0002-9285-2328
Andrea NataliDepartment of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy.ORCID http://orcid.org/0000-0002-8465-7717
Ele FerranniniCNR Institute of Clinical Physiology, Pisa, Italy.ORCID http://orcid.org/0000-0002-1384-1584

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

aims/hypothesisSodium-glucose cotransporter 2 (SGLT2) inhibitors provide cardiovascular and renal protection in type 2 diabetes and chronic kidney disease (CKD). Although both excess and restricted sodium intake are linked to adverse outcomes, the interaction of sodium intake with SGLT2 inhibitors has not been explored. This study aimed to examine how dietary sodium intake affects cardiorenal outcomes and whether canagliflozin modifies these effects.

methodsA post hoc analysis of the CREDENCE trial (median follow-up 2.6 years) was conducted in individuals with type 2 diabetes and CKD randomised to canagliflozin 100 mg or placebo. Using a validated formula, we estimated daily sodium intake from urine in 2573 participants, divided into low-normal sodium (LNS; n=1286) and high sodium (HS; n=1287) groups. Outcomes included the following: cardiovascular death or hospitalisation for heart failure; heart failure alone; a composite renal outcome; and all-cause death. Cox models were adjusted for confounders. Sodium intake was additionally analysed as a continuous variable to assess non-linearity.

resultsIn the placebo group, LNS intake increased the risk of heart failure/cardiovascular death vs HS (adjusted HR [adjHR] 1.56 [95% CI 1.10, 2.23]). Canagliflozin significantly reduced this risk in the LNS group (adjHR 0.48 [95% CI 0.33, 0.70]) but not in the HS group (adjHR 1.05 [95% CI 0.73, 1.53]). Similar patterns were seen for heart failure alone. Sodium intake had no effect on renal outcomes, while canagliflozin reduced renal risk in both the LNS group and the HS group. Neither sodium intake nor canagliflozin influenced all-cause mortality. Continuous modelling revealed a near-linear rise in heart failure/cardiovascular death risk as sodium intake decreased in placebo recipients, while this gradient was flattened with canagliflozin. CONCLUSIONS/

interpretationIn individuals with type 2 diabetes and CKD, LNS intake increases the risk of heart failure and cardiovascular death, while renal outcomes are unaffected by sodium intake. Canagliflozin mitigates the increased cardiovascular risk in individuals with LNS intake, while offering renal protection irrespective of dietary sodium.

trial registrationClinicaltrial.gov NCT02065791.

Indexed as

CanagliflozinDiabetes Mellitus, Type 2Sodium, DietarySodium-Glucose Transporter 2 InhibitorsAgedFemaleHeart FailureHumansMaleMiddle AgedRenal Insufficiency, ChronicCanagliflozinSodium, DietarySodium-Glucose Transporter 2 InhibitorsChronic kidney diseaseDiabetesHeart failureSodium

Identifiers

PMID41817689

What Socratic holds

Texttitle and abstract
Read underepoch 390

Registered trials

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 Socratic graph.