Trial reportDiabetes care2024

Effect of Semaglutide on Regression and Progression of Glycemia in People With Overweight or Obesity but Without Diabetes in the SELECT Trial.

Steven E Kahn, John E Deanfield, Ole Kleist Jeppesen, Scott S Emerson, Trine Welløv Boesgaard, Helen M Colhoun, Robert F Kushner, Ildiko Lingvay, Bartolome Burguera, Grzegorz Gajos and 10 more

Registry-linked trialAbstract readRandomized Controlled TrialMulticenter Study
In one paragraph

Trial report in Diabetes care, 2024. The graph read 1 number from its abstract, feeding 1 cell of the map, but none could be read as for or against, so it casts no vote. It is linked to trial NCT07654062 (Efficacy and Safety of Mazdutide in Adults With Prediabetes), which is not on this map. Cited by 44 papers, 2 of them syntheses that pooled it.

1number the graph read from it
0cells of the map it votes in
44citing 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.

Read, but not usablea number the graph found but could not read as for or against

Glycemic controlcomparator not stated · obesityfeeds one cell of the map
increase -0.32-0.33 to -0.30
Thereafter, HbA1c increased similarly in both arms, with a mean difference of -0.32 percentage points (95% CI -0.33 to -0.30; -3.49 mmol/mol [-3.66 to -3.32]) and with the difference favoring semaglutide throughout the study (P < 0.0001).

clause the extractor read what became the number

2 · Its place on the map

Where it lands on the map

Rows are treatments, columns are outcomes. The coloured squares are the cells this paper feeds, coloured by the vote it casts there. Click one to jump to what this paper adds to it.

supports the treatmentfavours the comparatorno clear differenceread, but no usable result
3 · What it changes

What it adds to each cell

For every cell the paper feeds: the belief in the claim with and without this paper, and this paper's estimate drawn against every other readable study in the cell. The ringed dot is this paper.

GLP-1 receptor agonists×glycemic control

No readable resultOpen on the map →What to test next →

40 readable studies in this cell: 97 favour the treatment, 16 find no difference, 10 favour the comparator.

Belief with this paper
0.91replicated · 68 families support, 7 contradict · against placebo
Without itNot a counted family in this claim, so removing it changes nothing.
← favours the treatmentfavours the comparator →
0 · no effect
NCT017204463,297 enrolled · 2013
Δ -0.66-0.80 to -0.52
NCT036893742,274 enrolled · 2018
Δ -0.29-0.38 to -0.20
NCT039879191,879 enrolled · 2019
Δ -0.51-0.64 to -0.38
NCT026078651,864 enrolled · 2016
Δ -0.50-0.60 to -0.40
NCT013360231,663 enrolled · 2011
Treatment contrast -0.64-0.75 to -0.53
NCT040178321,441 enrolled · 2019
Δ -0.20-0.30 to -0.10
NCT018365231,398 enrolled · 2013
Δ -0.20-0.32 to -0.07
NCT019301881,231 enrolled · 2013
Δ -1.06-1.21 to -0.91
NCT007344741,202 enrolled · 2008
Δ -0.71-0.87 to -0.55
NCT020581471,170 enrolled · 2014
Δ -0.29-0.38 to -0.19
NCT003184611,091 enrolled · 2006
Δ -1.09-1.30 to -0.88
NCT021289321,089 enrolled · 2014
Δ -0.81-0.96 to -0.67

This paper's own estimate is on a different scale from the rest of the cell, so it is not drawn here.

4 · 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.

NCT07654062 phase4not yet recruitingnot on this mapstarted 2026, after this paper: background citation

Efficacy and Safety of Mazdutide in Adults With Prediabetes: A Multicenter, Randomized, Double-Blind, Placebo-Controlled Clinical Trial (DREAM-PRE)

TypeinterventionalSponsorShandong Provincial HospitalRan2026 to 2029Enrolled150ConditionsPrediabetes, Impaired Fasting Glucose, Impaired Glucose Tolerance (Prediabetes)ArmsMazdutide, Placebo, Standardized Lifestyle Intervention
5 · Its place in the literature

Who cites it

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

  1. Guideline
  2. Pooled it
  3. Trial
  4. Trial
  5. Trial
  6. Trial
  7. Trial
  8. Trial
  9. Review
  10. Article
  11. Article
  12. Review
  13. Article
  14. Article
  15. Review
  16. Article
  17. Review
  18. GLP-1 and the cardiovascular system.The Journal of clinical investigation · 2026
    Review
  19. Review
  20. Observational
6 · The record

Corrections and comments

7 · Who and what money

Authors and funding

20 authors.

Steven E KahnDivision of Metabolism, Endocrinology and Nutrition, Department of Medicine, VA Puget Sound Health Care System and University of Washington, Seattle.ORCID 0000-0001-7307-9002
John E DeanfieldInstitute of Cardiovascular Science, University College London, London, U.K.
Ole Kleist JeppesenNovo Nordisk A/S, Søborg, Denmark.
Scott S EmersonDepartment of Biostatistics, University of Washington, Seattle, WA.
Trine Welløv BoesgaardNovo Nordisk A/S, Søborg, Denmark.
Helen M ColhounInstitute of Genetics and Cancer, University of Edinburgh, Edinburgh, U.K.
Robert F KushnerDepartment of Medicine, Northwestern University Feinberg School of Medicine, Northwestern University, Chicago, IL.
Ildiko LingvayDepartment of Internal Medicine/Endocrinology and Peter O'Donnell Jr. School of Public Health, University of Texas Southwestern Medical Center, Dallas, TX.ORCID 0000-0001-7006-7401
Bartolome BurgueraEndocrinology & Metabolism Institute, Cleveland Clinic, Cleveland, OH.
Grzegorz GajosDepartment of Coronary Artery Disease and Heart Failure, Jagiellonian University Medical College, Kraków, Poland.
Deborah Bade HornDepartment of Surgery, John P. and Katherine G. McGovern Medical School, University of Texas, Houston, TX.
Irene M HramiakWestern University, London, Ontario, Canada.
Ania M JastreboffEndocrinology and Metabolism, Department of Medicine, and Pediatric Endocrinology, Department of Pediatrics, Yale School of Medicine, New Haven, CT.
Alexander KokkinosFirst Department of Propaedeutic Internal Medicine, Medical School, National and Kapodistrian University of Athens, Athens, Greece.
Michael MaengDepartment of Cardiology, Aarhus University Hospital, and Department of Clinical Medicine, Aarhus University, Aarhus, Denmark.
Ana Laura S A MatosNovo Nordisk A/S, Søborg, Denmark.
Francisco J TinahonesInstituto de Investigación Biomédica de Málaga y Plataforma en Nanomedicina (IBIMA Plataforma BIONAND), CIBERobn, and Department of Endocrinology and Nutrition, Virgen de la Victoria University Hospital, Malaga University, Málaga, Spain.
A Michael LincoffDepartment of Cardiovascular Medicine, Cleveland Clinic, and Cleveland Clinic Lerner College of Medicine, Case Western Reserve University, Cleveland, OH.
Donna H RyanDivision of Metabolism, Endocrinology and Nutrition, Department of Medicine, VA Puget Sound Health Care System and University of Washington, Seattle.
SELECT Trial Investigators

Funding

Yale Clinical and Translational Science AwardUL1TR001863 · YALE UNIVERSITY · 2025 to 2025
$9.9M
BayerEli Lilly & CompanyJanssenNCATS NIH HHS UL1 TR001863Novo Nordisk NNF22OC0074083Novo Nordisk A/S GPP 2022PhilipsSquibbThe SELECT Trial InvestigatorsVerve Therapeutics
8 · The paper itself

Abstract

The marked sentences are the ones the graph read a number from.

objectiveTo determine whether semaglutide slows progression of glycemia in people with cardiovascular disease and overweight or obesity but without diabetes. RESEARCH DESIGN AND

methodsIn a multicenter, double-blind trial, participants aged ≥45 years, with BMI ≥27 kg/m2, and with preexisting cardiovascular disease but without diabetes (HbA1c <6.5%) were randomized to receive subcutaneous semaglutide (2.4 mg weekly) or placebo. Major glycemic outcomes were HbA1c and proportions achieving biochemical normoglycemia (HbA1c <5.7%) and progressing to biochemical diabetes (HbA1c ≥6.5%).

resultsOf 17,604 participants, 8,803 were assigned to semaglutide and 8,801 to placebo. Mean ± SD intervention exposure was 152 ± 56 weeks and follow-up 176 ± 40 weeks. In both treatment arms mean nadir HbA1c for participants was at 20 weeks. Thereafter, HbA1c increased similarly in both arms, with a mean difference of -0.32 percentage points (95% CI -0.33 to -0.30; -3.49 mmol/mol [-3.66 to -3.32]) and with the difference favoring semaglutide throughout the study (P < 0.0001). Body weight plateaued at 65 weeks and was 8.9% lower with semaglutide. At week 156, a greater proportion treated with semaglutide were normoglycemic (69.5% vs. 35.8%; P < 0.0001) and a smaller proportion had biochemical diabetes by week 156 (1.5% vs. 6.9%; P < 0.0001). The number needed to treat was 18.5 to prevent a case of diabetes. Both regression and progression were dependent on glycemia at baseline, with the magnitude of weight reduction important in mediating 24.5% of progression and 27.1% of regression.

conclusionsIn people with preexisting cardiovascular disease and overweight or obesity but without diabetes, long-term semaglutide increases regression to biochemical normoglycemia and reduces progression to biochemical diabetes but does not slow glycemic progression over time.

Indexed as

Blood GlucoseGlucagon-Like PeptidesGlycated HemoglobinObesityOverweightAgedDouble-Blind MethodFemaleHumansHypoglycemic AgentsMaleMiddle AgedSemaglutideBlood GlucoseGlucagon-Like PeptidesGlycated HemoglobinHypoglycemic AgentsSemaglutide

Identifiers

PMID38907683
PMCPMC11282386

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.