Trial reportThe New England journal of medicine2025

Cagrilintide-Semaglutide in Adults with Overweight or Obesity and Type 2 Diabetes.

Melanie J Davies, Harpreet S Bajaj, Christa Broholm, Astrid Eliasen, W Timothy Garvey, Carel W le Roux, Ildiko Lingvay, Christian Bøge Lyndgaard, Julio Rosenstock, Sue D Pedersen and 1 more

Registry-linked trialAbstract readRandomized Controlled TrialClinical Trial, Phase IIIMulticenter Study
PubMed Publisher
In one paragraph

Trial report in The New England journal of medicine, 2025. The graph read 1 number from its abstract, feeding 2 cells of the map: it supports the treatment in 2. It reports registered trial NCT05394519. Cited by 55 papers, 2 of them syntheses that pooled it.

1number the graph read from it
2cells of the map it votes in
55citing 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.

← favours the treatmentfavours the comparator →
-11.20 · no effect
Mean change in body weight from baseline to week 68cagrilintide-semaglutide (2.4 mg each) vs placebofavours the treatment · t2d, obesityfeeds 2 cells of the map
Δ -10.4-11.2 to -9.50P<0.001
The estimated mean change in body weight from baseline to week 68 was -13.7% in the cagrilintide-semaglutide group and -3.4% in the placebo group (estimated difference, -10.4 percentage points; 95% confidence interval, -11.2 to -9.5; P<0.001).

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.

GIP/GLP-1 & amylin agonists×body weight & composition

SupportsOpen on the map →What to test next →

29 readable studies in this cell: 28 favour the treatment, 1 find no difference, 0 favour the comparator.

Belief with this paper
1.00replicated · 19 families support, 0 contradict · against placebo
Without it
1.00This paper does not move the number.
← favours the treatmentfavours the comparator →
0 · no effect
This paper1,200 enrolled · 2023
Δ -10.4-11.2 to -9.50
Δ -17.3-18.1 to -16.6
NCT041846222,539 enrolled · 2019
Δ -13.5-14.6 to -12.5
NCT037306622,002 enrolled · 2018
Δ -9.00-9.80 to -8.30
NCT039879191,879 enrolled · 2019
Δ -1.70-2.60 to -0.70
NCT038829701,444 enrolled · 2019
Δ -9.80-10.8 to -8.80
NCT045379231,428 enrolled · 2020
Δ -10.7-11.5 to -9.90
NCT04657003938 enrolled · 2021
Δ -10.1-11.5 to -8.80
NCT04093752917 enrolled · 2019
Δ -6.50-7.40 to -5.60
NCT04660643783 enrolled · 2021
Δ -21.4-22.9 to -20.0
NCT05822830751 enrolled · 2023
Δ -6.50-8.10 to -4.90
NCT04847557731 enrolled · 2021
Δ -11.6-12.8 to -10.4
NCT03861052636 enrolled · 2019
Δ -5.20-6.40 to -4.10

GLP-1 receptor agonists×body weight & composition

SupportsOpen 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 it
0.90This paper does not move the number.
← favours the treatmentfavours the comparator →
0 · no effect
This paper1,200 enrolled · 2023
Δ -10.4-11.2 to -9.50
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
NCT020581471,170 enrolled · 2014
Δ 14.38.37 to 20.3
NCT003184611,091 enrolled · 2006
Δ -1.29-2.16 to -0.41
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.

NCT05394519 phase3completed

Efficacy and Safety of Cagrilintide s.c. 2.4 mg in Combination With Semaglutide s.c. 2.4 mg (CagriSema s.c. 2.4 mg/2.4 mg) Once-weekly in Participants With Overweight or Obesity and Type 2 Diabetes

Ran2023Enrolled1,200Registered outcomes36Posted comparisons0ConditionsObesity, Overweight, Type 2 Diabetes MellitusArmsCagrilintide, Placebo cagrilintide, Placebo semaglutide, semaglutide
Open the trial in the graph
5 · Its place in the literature

Who cites it

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

  1. Pooled it
  2. Pooled it
  3. Trial
  4. Article
  5. Review
  6. The evolving landscape of obesity pharmacotherapy.Nature reviews. Drug discovery · 2026
    Review
  7. Article
  8. Review
  9. Article
  10. Article
  11. Review
  12. Review
  13. Review
  14. Article
  15. Article
  16. Review
  17. Review
  18. Review
  19. Article
  20. 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

11 authors.

Melanie J DaviesDiabetes Research Centre, University of Leicester, Leicester, United Kingdom.
Harpreet S BajajEndocrine and Metabolic Research, LMC Healthcare, Brampton, ON, Canada.
Christa BroholmNovo Nordisk, Søborg, Denmark.
Astrid EliasenNovo Nordisk, Søborg, Denmark.
W Timothy GarveyDepartment of Nutrition Sciences, University of Alabama at Birmingham, Birmingham.
Carel W le RouxDiabetes Complications Research Centre, University College Dublin School of Medicine, Dublin.
Ildiko LingvayDepartment of Internal Medicine, Endocrinology Division, University of Texas Southwestern Medical Center, Dallas.ORCID 0000-0001-7006-7401
Christian Bøge LyndgaardNovo Nordisk, Søborg, Denmark.
Julio RosenstockVelocity Clinical Research at Medical City, Dallas.ORCID 0000-0001-8324-3275
Sue D PedersenC-ENDO Diabetes and Endocrinology Clinic Calgary, Calgary, AB, Canada.
REDEFINE 2 Study Group

Funding

No grant is acknowledged in the PubMed record.

8 · The paper itself

Abstract

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

backgroundCagrilintide and semaglutide have each been shown to induce weight loss as monotherapies. Data are needed on the coadministration of cagrilintide and semaglutide (called CagriSema) for weight management in adults with type 2 diabetes, including those in a subgroup who are undergoing continuous glucose monitoring.

methodsIn this phase 3a, double-blind, randomized, placebo-controlled trial conducted in 12 countries, we assigned adults with a body-mass index of 27 or more, a glycated hemoglobin level of 7 to 10%, and type 2 diabetes in a 3:1 ratio to receive once-weekly cagrilintide-semaglutide (2.4 mg each) or placebo, along with lifestyle intervention, for 68 weeks. The two primary end points were the percent change in body weight and the percentage of patients with a weight reduction of at least 5%. Additional end points were changes in glycemic measures and safety assessments. Effect estimates were calculated with the use of the treatment-policy estimand (consistent with the intention-to-treat principle).

resultsA total of 1206 patients underwent randomization to either the cagrilintide-semaglutide group (904 patients) or the placebo group (302 patients). The estimated mean change in body weight from baseline to week 68 was -13.7% in the cagrilintide-semaglutide group and -3.4% in the placebo group (estimated difference, -10.4 percentage points; 95% confidence interval, -11.2 to -9.5; P<0.001). More patients in the cagrilintide-semaglutide group than in the placebo group had a weight reduction of 5% or more (P<0.001); the same was true of reductions of at least 10%, 15%, and 20% (P<0.001 for the last comparison). The percentage of patients who had a glycated hemoglobin level of 6.5% or less was 73.5% in the cagrilintide-semaglutide group and 15.9% in the placebo group. Gastrointestinal adverse events were reported by 72.5% of the patients in the cagrilintide-semaglutide group and 34.4% in the placebo group, most of which were transient and mild or moderate in severity.

conclusionsOnce-weekly cagrilintide-semaglutide (at a dose of 2.4 mg each) resulted in a significantly lower body weight than placebo in adults with obesity and type 2 diabetes. (Funded by Novo Nordisk; REDEFINE 2 ClinicalTrials.gov number, NCT05394519.).

Indexed as

Diabetes Mellitus, Type 2Glucagon-Like Peptide-1 Receptor AgonistsIslet Amyloid PolypeptideObesityOverweightWeight LossAdultAgedBlood GlucoseBody Mass IndexContinuous Glucose MonitoringDouble-Blind MethodDrug CombinationsFemaleGlucagon-Like Peptide 1Glycated HemoglobinBlood GlucosecagrilintideDrug CombinationsGlucagon-Like Peptide 1Glucagon-Like Peptide-1 Receptor AgonistsGlycated HemoglobinIslet Amyloid PolypeptideSemaglutide

Identifiers

PMID40544432

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.