Evidence map›Paper›PMID 29178519›Full record

Trial reportDiabetes, obesity & metabolism2018

Semaglutide, reduction in glycated haemoglobin and the risk of diabetic retinopathy.

Tina Vilsbøll, Stephen C Bain, Lawrence A Leiter, Ildiko Lingvay, David Matthews, Rafael Simó, Ida Carøe Helmark, Nelun Wijayasinghe, Michael Larsen

Registry-linked trialOpen access · hybridAbstract readMulticenter StudyRandomized Controlled Trial
PubMed Full text at PMC Publisher
In one paragraph

Trial report in Diabetes, obesity & metabolism, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It reports registered trial NCT01720446. Cited by 127 papers, 4 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
127citing papers in PubMed, 4 pooled it
18.6field-weighted citation impact, top 1% 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.

NCT01720446 phase3completed

A Long-term, Randomised, Double-blind, Placebo-controlled, Multinational, Multi-centre Trial to Evaluate Cardiovascular and Other Long-term Outcomes With Semaglutide in Subjects With Type 2 Diabetes (SUSTAIN™ 6 - Long-term Outcomes)

Ran2013Enrolled3,297Registered outcomes16Posted comparisons54ConditionsDiabetes, Diabetes Mellitus, Type 2ArmsPlacebo, semaglutide
PMID 31167654PMID 30615985PMID 30851070PMID 27633186PMID 29907893other papers from this trial
Open the trial in the graph
3 · Its place in the literature

Who cites it

127 citing papers in PubMed, 4 syntheses or guidelines pooled it, 281 citations in OpenAlex.

  1. Pooled it
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  8. Semaglutide Added to Basal Insulin in Type 2 Diabetes (SUSTAIN 5): A Randomized, Controlled Trial.The Journal of clinical endocrinology and metabolism · 2018 · on this map
    Trial
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  10. Glucagon-like peptide-1 receptor agonists and diabetic retinopathy: a systematic review of diabetic retinopathy outcomes.Graefe's archive for clinical and experimental ophthalmology = Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie · 2026
    Review
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  13. Exposure to GLP-1RA and Risk of Structural Progression in Differentiated Thyroid Cancer.The Journal of clinical endocrinology and metabolism · 2026
    Observational
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67 more citing papers are in PubMed but not listed here.

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

9 authors at 7 institutions in 5 countries.

Tina VilsbøllSteno Diabetes Center Copenhagen, University of Copenhagen, Gentofte, Denmark.ORCID 0000-0002-0456-6787
Stephen C BainSchool of Medicine, Swansea University, Swansea, UK.
Lawrence A LeiterLi Ka Shing Knowledge Institute, St. Michael's Hospital, University of Toronto, Ontario, Canada.ORCID 0000-0002-1040-6229
Ildiko LingvayUniversity of Texas Southwestern Medical Center, Dallas, Texas.ORCID 0000-0001-7006-7401
David MatthewsOxford Centre for Diabetes, Endocrinology and Metabolism, and Harris Manchester College, University of Oxford, Oxford, UK.
Rafael SimóDiabetes and Metabolism Research Unit, Vall d'Hebron Research Institute, Barcelona and CIBERDEM (ISCIII), Madrid, Spain.
Ida Carøe HelmarkNovo Nordisk, Søborg, Denmark.
Nelun WijayasingheNovo Nordisk, Søborg, Denmark.
Michael LarsenDepartment of Ophthalmology, Rigshospitalet and Department of Clinical Medicine, University of Copenhagen, Copenhagen, Denmark.
Novo Nordisk (Denmark) · DKUniversity of Copenhagen · DKInstituto de Salud Carlos III · ESSt. Michael's Hospital · CASwansea University · GBThe University of Texas Southwestern Medical Center · USUniversity of Oxford · GB

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

aimsTo evaluate diabetic retinopathy (DR) data from across the SUSTAIN clinical trial programme. MATERIALS AND

methodsThe SUSTAIN clinical trial programme evaluated the efficacy and safety of semaglutide, a glucagon-like peptide-1 analogue, for the treatment of type 2 diabetes (T2D). In SUSTAIN 6, a 2-year, pre-approval cardiovascular outcomes trial, semaglutide was associated with a significant increase in the risk of DR complications (DRC) vs placebo. DR data from across the SUSTAIN trials were evaluated, and post hoc analyses of the SUSTAIN 6 data were conducted. These included subgroup analyses to identify at-risk patients and a mediation analysis with initial change in glycated haemoglobin (HbA1c; percentage-points at week 16) as a covariate, to examine the role of the magnitude of reduction in HbA1c as an intermediate factor affecting risk of DRC.

resultsThere was no imbalance in DR adverse events across the SUSTAIN 1 to 5 and Japanese trials. The majority of the effect with semaglutide vs placebo in SUSTAIN 6 may be attributed to the magnitude and rapidity of HbA1c reduction during the first 16 weeks of treatment in patients who had pre-existing DR and poor glycaemic control at baseline, and who were treated with insulin.

conclusionsEarly worsening of DR is a known phenomenon associated with the rapidity and magnitude of improvement in glycaemic control with insulin; the DRC findings in SUSTAIN 6 are consistent with this. Guidance regarding the early worsening of DR is recommended with insulin. Similar recommendations may be appropriate for semaglutide.

Indexed as

AdultAgedBlood GlucoseDiabetes Mellitus, Type 2Diabetic RetinopathyFemaleGlucagon-Like PeptidesGlycated HemoglobinHumansJapanMaleMiddle AgedRisk FactorsSemaglutideBlood GlucoseGlucagon-Like PeptidesGlycated HemoglobinSemaglutideantidiabetic drugdiabetic retinopathyGLP-1 analogue

Identifiers

PMID29178519
PMCPMC5888154
OpenAlexW2785139619

What Socratic holds

Texttitle and abstract
LicenceCC BY-NC
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.