Evidence mapPaperPMID 31640705Full record

ArticleCardiovascular diabetology2019

Effects of exenatide and open-label SGLT2 inhibitor treatment, given in parallel or sequentially, on mortality and cardiovascular and renal outcomes in type 2 diabetes: insights from the EXSCEL trial.

Lindsay E Clegg, Robert C Penland, Srinivas Bachina, David W Boulton, Marcus Thuresson, Hiddo J L Heerspink, Stephanie Gustavson, C David Sjöström, James A Ruggles, Adrian F Hernandez and 3 more

Registry-linked trialOpen access · goldAbstract read
In one paragraph

Article in Cardiovascular diabetology, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT01144338 (Exenatide Study of Cardiovascular Event Lowering Trial), which is not on this map. Cited by 47 papers, 7 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
47citing papers in PubMed, 7 pooled it
7.5field-weighted citation impact, top 2% of its field
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.

NCT01144338 phase3completednot on this map

Exenatide Study of Cardiovascular Event Lowering Trial (EXSCEL). A Randomized, Placebo Controlled Clinical Trial to Evaluate Cardiovascular Outcomes After Treatment With Exenatide Once Weekly in Patients With Type 2 Diabetes Mellitus.

TypeinterventionalSponsorAstraZenecaRan2010 to 2017Enrolled14,752ConditionsType 2 Diabetes MellitusArmsExenatide Once Weekly, Placebo
3 · Its place in the literature

Who cites it

47 citing papers in PubMed, 7 syntheses or guidelines pooled it, 89 citations in OpenAlex.

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  18. Upcoming drug targets for kidney protective effects in chronic kidney disease.Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association · 2025
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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

13 authors at 8 institutions in 6 countries.

Lindsay E CleggClinical Pharmacology and Safety Sciences, R&D, AstraZeneca, 1 MedImmune Way, Gaithersburg, MD, 20878, USA. lindsay.clegg1@astrazeneca.com.ORCID 0000-0001-8558-9341
Robert C PenlandClinical Pharmacology and Safety Sciences, R&D, AstraZeneca, Boston, USA.
Srinivas BachinaClinical Pharmacology and Safety Sciences, R&D, AstraZeneca, Boston, USA.
David W BoultonClinical Pharmacology and Safety Sciences, R&D, AstraZeneca, 1 MedImmune Way, Gaithersburg, MD, 20878, USA.
Marcus ThuressonStatisticon AB, Uppsala, Sweden.
Hiddo J L HeerspinkDepartment of Clinical Pharmacy and Pharmacology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
Stephanie GustavsonBioPharmaceuticals R&D, AstraZeneca, Gaithersburg, MD, USA.
C David SjöströmBioPharmaceuticals R&D, AstraZeneca, Gothenburg, Sweden.
James A RugglesBioPharmaceuticals, AstraZeneca, Wilmington, DE, USA.
Adrian F HernandezDuke University and Duke Clinical Research Institute, Duke University School of Medicine, Durham, NC, USA.
John B BuseUniversity of North Carolina School of Medicine, Chapel Hill, NC, USA.
Robert J MentzDuke University and Duke Clinical Research Institute, Duke University School of Medicine, Durham, NC, USA.
Rury R HolmanDiabetes Trials Unit, University of Oxford, Oxford, UK.
AstraZeneca (United States) · USDuke University · USAstraZeneca (France) · FRAstraZeneca (Sweden) · SEStatisticon (Sweden) · SEUniversity Medical Center Groningen · NLUniversity of North Carolina at Chapel Hill · USUniversity of Oxford · GB

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundSodium-glucose cotransporter-2 inhibitors (SGLT2i) and glucagon-like peptide-1 receptor agonists (GLP-1 RA) improve cardiovascular and renal outcomes in patients with type 2 diabetes through distinct mechanisms. However, evidence on clinical outcomes in patients treated with both GLP-1 RA and SGLT2i is lacking. We aim to provide insight into the effects of open-label SGLT2i use in parallel with or shortly after once-weekly GLP-1 RA exenatide (EQW) on cardiorenal outcomes.

methodsIn the EXSCEL cardiovascular outcomes trial EQW arm, SGLT2i drop-in occurred in 8.7% of participants. These EQW+SGLT2i users were propensity-matched to: (1) placebo-arm participants not taking SGLT2i (n = 572 per group); and to (2) EQW-arm participants not taking SGLT2i (n = 575), based on their last measured characteristics before SGLT2i initiation, and equivalent study visit in comparator groups. Time-to-first major adverse cardiovascular event (MACE) and all-cause mortality (ACM) were compared using Cox regression analyses. eGFR slopes were quantified using mixed model repeated measurement analyses.

resultsIn adjusted analyses, the risk for MACE with combination EQW+SGLT2i use was numerically lower compared with both placebo (adjusted hazard ratio 0.68, 95% CI 0.39-1.17) and EQW alone (0.85, 0.48-1.49). Risk of ACM was nominally significantly reduced compared with placebo (0.38, 0.16-0.90) and compared with EQW (0.41, 0.17-0.95). Combination EQW+SGLT2i use also nominally significantly improved estimated eGFR slope compared with placebo (+ 1.94, 95% CI 0.94-2.94 mL/min/1.73 m

conclusionsThis post hoc analysis supports the hypothesis that combinatorial EQW and SGLT2i therapy may provide benefit on cardiovascular outcomes and mortality. Trial registration Clinicaltrials.gov, Identifying number: NCT01144338, Date of registration: June 15, 2010.

Indexed as

AgedCardiovascular DiseasesCause of DeathDiabetes Mellitus, Type 2Drug Administration ScheduleDrug Therapy, CombinationExenatideFemaleGlomerular Filtration RateHumansIncretinsKidneyMaleMiddle AgedMulticenter Studies as TopicRandomized Controlled Trials as TopicExenatideIncretinsSodium-Glucose Transporter 2 InhibitorsCardiovascular outcomesCombination therapyeGFR slopeExenatideGLP-1 receptor agonistPropensity score matchingSGLT2 inhibitorType 2 diabetes mellitus

Identifiers

PMID31640705
PMCPMC6805385
OpenAlexW2981486868

What Socratic holds

Textmetadata
LicenceCC BY
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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.