Trial reportDiabetes care2025

High-Dose Semaglutide (Up to 16 mg) in People With Type 2 Diabetes and Overweight or Obesity: A Randomized, Placebo-Controlled, Phase 2 Trial.

Vanita R Aroda, Nils B Jørgensen, Bharath Kumar, Ildiko Lingvay, Anne Sofie Laulund, John B Buse, trial investigators

Abstract readRandomized Controlled TrialClinical Trial, Phase II
In one paragraph

Trial report in Diabetes care, 2025. The graph read 4 numbers from its abstract, feeding 2 cells of the map, but none could be read as for or against, so it casts no vote. Cited by 10 papers, 1 of them a synthesis that pooled it.

4numbers the graph read from it
0cells of the map it votes in
10citing papers in PubMed, 1 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

HbA1c changesemaglutide 16 mg vs semaglutide 2 mg, in treatment policy estimandcomparator not stated · t2d, obesityfeeds one cell of the map
Δ -0.30-0.70 to 0.20
RESULTS: Estimated treatment difference between 16 and 2 mg was -0.3 percentage points (%-points) (95% CI -0.7 to 0.2; P = 0.245) for HbA1c change and -3.4 kg (-6.0 to -0.8; P = 0.011) for weight change for the treatment policy estimand and -0.5%-points (-1.0 to -0.1; P = 0.015) and -4.5 kg (-7.6 to -1.4; P = 0.004), respectively, for the hypothetical estimand.
Weight changesemaglutide 16 mg vs semaglutide 2 mg, in hypothetical estimandcomparator not stated · t2d, obesityfeeds one cell of the map
Δ -4.50-7.60 to -1.40
RESULTS: Estimated treatment difference between 16 and 2 mg was -0.3 percentage points (%-points) (95% CI -0.7 to 0.2; P = 0.245) for HbA1c change and -3.4 kg (-6.0 to -0.8; P = 0.011) for weight change for the treatment policy estimand and -0.5%-points (-1.0 to -0.1; P = 0.015) and -4.5 kg (-7.6 to -1.4; P = 0.004), respectively, for the hypothetical estimand.
Weight changesemaglutide 16 mg vs semaglutide 2 mg, in treatment policy estimandcomparator not stated · t2d, obesityfeeds one cell of the map
Δ -3.40-6.00 to -0.80
RESULTS: Estimated treatment difference between 16 and 2 mg was -0.3 percentage points (%-points) (95% CI -0.7 to 0.2; P = 0.245) for HbA1c change and -3.4 kg (-6.0 to -0.8; P = 0.011) for weight change for the treatment policy estimand and -0.5%-points (-1.0 to -0.1; P = 0.015) and -4.5 kg (-7.6 to -1.4; P = 0.004), respectively, for the hypothetical estimand.
HbA1c changesemaglutide 16 mg vs semaglutide 2 mg, in hypothetical estimandcomparator not stated · t2d, obesityfeeds one cell of the map
Δ -0.50-1.00 to -0.10
RESULTS: Estimated treatment difference between 16 and 2 mg was -0.3 percentage points (%-points) (95% CI -0.7 to 0.2; P = 0.245) for HbA1c change and -3.4 kg (-6.0 to -0.8; P = 0.011) for weight change for the treatment policy estimand and -0.5%-points (-1.0 to -0.1; P = 0.015) and -4.5 kg (-7.6 to -1.4; P = 0.004), respectively, for the hypothetical estimand.

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: 96 favour the treatment, 17 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.

GLP-1 receptor agonists×body weight & composition

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

40 readable studies in this cell: 83 favour the treatment, 15 find no difference, 11 favour the comparator.

Belief with this paper
0.90replicated · 64 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
NCT012722193,731 enrolled · 2011
Δ -5.39-5.82 to -4.95
Δ -17.3-18.1 to -16.6
NCT017204463,297 enrolled · 2013
Δ -2.95-3.47 to -2.44
NCT035489351,961 enrolled · 2018
Δ -12.4-13.4 to -11.5
NCT039879191,879 enrolled · 2019
Δ -1.70-2.60 to -0.70
NCT026078651,864 enrolled · 2016
Δ -2.50-3.00 to -2.00
NCT056467061,407 enrolled · 2023
Δ -14.8-16.2 to -13.4
NCT018365231,398 enrolled · 2013
Δ -4.90-5.65 to -4.16
NCT035527571,210 enrolled · 2018
Δ -6.21-7.28 to -5.15
NCT007344741,202 enrolled · 2008
Δ -1.50-2.08 to -0.92
Δ -10.4-11.2 to -9.50
NCT020581471,170 enrolled · 2014
Δ 14.38.37 to 20.3

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.

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

5 · Its place in the literature

Who cites it

10 citing papers in PubMed, 1 synthesis or guideline pooled it.

  1. Pooled it
  2. The evolving landscape of obesity pharmacotherapy.Nature reviews. Drug discovery · 2026
    Review
  3. Article
  4. Review
  5. Review
  6. Article
  7. Article
  8. Article
  9. Article
  10. Position Statement on Cardiometabolic Health Across the Woman's Life Course - 2025.Revista brasileira de ginecologia e obstetricia : revista da Federacao Brasileira das Sociedades de Ginecologia e Obstetricia · 2025
    Article
6 · The record

Corrections and comments

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

7 · Who and what money

Authors and funding

7 authors.

Vanita R ArodaEndocrinology, Diabetes, and Hypertension, Brigham and Women's Hospital, Harvard Medical School, Boston, MA.ORCID 0000-0002-7706-4585
Nils B JørgensenNovo Nordisk A/S, Søborg, Denmark.
Bharath KumarBiostatistics, Novo Nordisk Service Centre India Private Ltd., Bangalore, India.
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
Anne Sofie LaulundNovo Nordisk A/S, Søborg, Denmark.
John B BuseDivision of Endocrinology, Department of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC.ORCID 0000-0002-9723-3876
trial investigators

Funding

North Carolina Translational and Clinical Sciences Institute (NC TraCS)UM1TR004406 · UNIV OF NORTH CAROLINA CHAPEL HILL · 2025 to 2025
$8.6M
Pilot & Feasibility ProgramP30DK124723 · WAKE FOREST UNIVERSITY HEALTH SCIENCES · 2025 to 2025
$1.6M
NCATS NIH HHS UM1 TR004406NIDDK NIH HHS P30 DK124723Novo Nordisk
8 · The paper itself

Abstract

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

objectiveStudies have demonstrated dose-dependent efficacy of glucagon-like peptide 1 receptor agonists for glycemic control and body weight. The aim of this trial was to characterize the dose-dependent effects of semaglutide (up to 16 mg/week) in people with type 2 diabetes and overweight or obesity. RESEARCH DESIGN AND

methodsIn this parallel-group, participant- and investigator-blinded, phase 2 trial, 245 individuals with type 2 diabetes and BMI ≥27 kg/m2 on metformin were randomized to weekly semaglutide (2, 8, or 16 mg s.c.) or placebo for 40 weeks. Doses were escalated every 4 weeks, followed by a maintenance period. Dose modifications were not allowed. Primary and secondary efficacy end points included change from baseline to week 40 in HbA1c and body weight, respectively.

resultsEstimated treatment difference between 16 and 2 mg was -0.3 percentage points (%-points) (95% CI -0.7 to 0.2; P = 0.245) for HbA1c change and -3.4 kg (-6.0 to -0.8; P = 0.011) for weight change for the treatment policy estimand and -0.5%-points (-1.0 to -0.1; P = 0.015) and -4.5 kg (-7.6 to -1.4; P = 0.004), respectively, for the hypothetical estimand. Dose-response modeling confirmed these findings. Treatment-emergent adverse events (AEs) and treatment discontinuations due to AEs, primarily gastrointestinal, were more frequent in the semaglutide 8 and 16 mg groups than in the 2 mg group. No severe hypoglycemic episodes were reported.

conclusionsHigher semaglutide doses for type 2 diabetes and overweight or obesity provide modest additional glucose-lowering effect, with additional weight loss, at the expense of more AEs and treatment discontinuations. A study for evaluating high-dose semaglutide in obesity is currently underway.

Indexed as

Diabetes Mellitus, Type 2Glucagon-Like PeptidesHypoglycemic AgentsObesityOverweightAdultAgedBlood GlucoseFemaleGlucagon-Like Peptide 1Glycated HemoglobinHumansMaleMetforminMiddle AgedSemaglutideBlood GlucoseGlucagon-Like Peptide 1Glucagon-Like PeptidesGlycated HemoglobinHypoglycemic AgentsMetforminSemaglutide

Identifiers

PMID40279144
PMCPMC12094194

What Socratic holds

Texttitle and abstract
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 Socratic graph.