Trial reportDiabetes, obesity & metabolism2025

Tirzepatide 10 and 15 mg versus semaglutide 2.4 mg in people with obesity or overweight with type 2 diabetes: An indirect treatment comparison.

Emily R Hankosky, Xuanyao He, Raleigh Malik, Julia Fraseur Brumm, Fangyu Wang, Anthony Niemeyer, Xiaotian M Zhang, W Timothy Garvey

Abstract readComparative StudyRandomized Controlled TrialMulticenter Study
In one paragraph

Trial report in Diabetes, obesity & metabolism, 2025. The graph read 6 numbers from its abstract, feeding 2 cells of the map, but none could be read as for or against, so it casts no vote. It also reports an association that does not count as treatment evidence, such as OR 1.76 (1.04 to 2.97) for weight reduction ≥5%. Cited by 4 papers.

6numbers the graph read from it
0cells of the map it votes in
4citing papers in PubMed
–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 (%) levelstirzepatide 10 mg vs semaglutide 2.4 mgan association or prognostic statement, not a treatment comparison · t2d, obesityfeeds one cell of the map
Δ 0.47<0.001
Tirzepatide 15 mg had significantly higher odds of achieving ≥5% weight reduction (odds ratio 15 mg: 1.76, 95% CI 1.04-2.97, p = 0.035; odds ratio 10 mg: 1.24, 95% CI 0.75-2.04, p = 0.407), and both tirzepatide doses were associated with significantly greater reductions in HbA1c (%) levels (mean difference, 10 mg: 0.47%; 15 mg: 0.56%, p < 0.001) than semaglutide.
Weight reduction ≥5%tirzepatide 10 mg vs semaglutide 2.4 mgan association or prognostic statement, not a treatment comparison · t2d, obesityfeeds one cell of the map
OR 1.240.75 to 2.040.407
Tirzepatide 15 mg had significantly higher odds of achieving ≥5% weight reduction (odds ratio 15 mg: 1.76, 95% CI 1.04-2.97, p = 0.035; odds ratio 10 mg: 1.24, 95% CI 0.75-2.04, p = 0.407), and both tirzepatide doses were associated with significantly greater reductions in HbA1c (%) levels (mean difference, 10 mg: 0.47%; 15 mg: 0.56%, p < 0.001) than semaglutide.
Weight reduction ≥5%tirzepatide 15 mg vs semaglutide 2.4 mgan association or prognostic statement, not a treatment comparison · t2d, obesityfeeds one cell of the map
OR 1.761.04 to 2.970.035
Tirzepatide 15 mg had significantly higher odds of achieving ≥5% weight reduction (odds ratio 15 mg: 1.76, 95% CI 1.04-2.97, p = 0.035; odds ratio 10 mg: 1.24, 95% CI 0.75-2.04, p = 0.407), and both tirzepatide doses were associated with significantly greater reductions in HbA1c (%) levels (mean difference, 10 mg: 0.47%; 15 mg: 0.56%, p < 0.001) than semaglutide.
Mean percent weight reductionstirzepatide 15 mg vs semaglutide 2.4 mgan association or prognostic statement, not a treatment comparison · t2d, obesityfeeds one cell of the map
Δ 4.79<0.01
RESULTS: Tirzepatide 10 and 15 mg were associated with significantly greater mean percent weight reductions versus semaglutide (mean difference, 10 mg: 2.57%; 15 mg: 4.79%, p < 0.01).
Mean percent weight reductionstirzepatide 10 mg vs semaglutide 2.4 mgan association or prognostic statement, not a treatment comparison · t2d, obesityfeeds one cell of the map
Δ 2.57<0.01
RESULTS: Tirzepatide 10 and 15 mg were associated with significantly greater mean percent weight reductions versus semaglutide (mean difference, 10 mg: 2.57%; 15 mg: 4.79%, p < 0.01).
HbA1c (%) levelstirzepatide 15 mg vs semaglutide 2.4 mgan association or prognostic statement, not a treatment comparison · t2d, obesityfeeds one cell of the map
Δ 0.56<0.001
Tirzepatide 15 mg had significantly higher odds of achieving ≥5% weight reduction (odds ratio 15 mg: 1.76, 95% CI 1.04-2.97, p = 0.035; odds ratio 10 mg: 1.24, 95% CI 0.75-2.04, p = 0.407), and both tirzepatide doses were associated with significantly greater reductions in HbA1c (%) levels (mean difference, 10 mg: 0.47%; 15 mg: 0.56%, p < 0.001) than semaglutide.

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×glycemic control

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

24 readable studies in this cell: 21 favour the treatment, 3 find no difference, 0 favour the comparator.

Belief with this paper
0.88established · 15 families support, 2 contradict · against placebo
Without itNot a counted family in this claim, so removing it changes nothing.
← favours the treatmentfavours the comparator →
0 · no effect
NCT041846222,539 enrolled · 2019
Δ -0.33-0.36 to -0.30
NCT037306622,002 enrolled · 2018
Δ -0.99-1.13 to -0.86
NCT039879191,879 enrolled · 2019
Δ -0.51-0.64 to -0.38
NCT038829701,444 enrolled · 2019
Δ -0.86-1.00 to -0.72
NCT045379231,428 enrolled · 2020
Δ -1.10-1.24 to -0.97
NCT04093752917 enrolled · 2019
Δ -1.49-1.69 to -1.29
NCT04660643783 enrolled · 2021
Δ -8.92-10.4 to -7.43
NCT03861052636 enrolled · 2019
Δ -1.09-1.27 to -0.90
NCT04657016579 enrolled · 2021
Δ -11.2-13.5 to -8.80
NCT03954834478 enrolled · 2019
Δ -1.91-2.18 to -1.63
NCT04039503475 enrolled · 2019
Δ -1.66-1.88 to -1.43
NCT03131687318 enrolled · 2017
Δ -0.80-1.20 to -0.40

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

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

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

28 readable studies in this cell: 27 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 itNot a counted family in this claim, so removing it changes nothing.
← favours the treatmentfavours the comparator →
0 · no effect
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
Δ -10.4-11.2 to -9.50
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

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

4 citing papers in PubMed.

  1. Trial
  2. Trial
  3. Article
  4. Review
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

8 authors.

Emily R HankoskyEli Lilly and Company, Indianapolis, Indiana, USA.ORCID https://orcid.org/0000-0001-9934-584X
Xuanyao HeEli Lilly and Company, Indianapolis, Indiana, USA.
Raleigh MalikEli Lilly and Company, Indianapolis, Indiana, USA.
Julia Fraseur BrummEli Lilly and Company, Indianapolis, Indiana, USA.
Fangyu WangEli Lilly and Company, Indianapolis, Indiana, USA.
Anthony NiemeyerEli Lilly and Company, Indianapolis, Indiana, USA.
Xiaotian M ZhangEli Lilly and Company, Indianapolis, Indiana, USA.
W Timothy GarveyUniversity of Alabama at Birmingham, Birmingham, Alabama, USA.ORCID https://orcid.org/0000-0003-0822-0860

Funding

Why is the prevalence of obesity so high in U.S. Southern States? Regional predictors of BMI and obesity treatment response.P30DK056336 · NIDDK · UNIVERSITY OF ALABAMA AT BIRMINGHAM · PI James O Hill · 2000 to 2026
$31.9M
Eli Lilly and CompanyNIDDK NIH HHS P30 DK056336
8 · The paper itself

Abstract

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

aimsTirzepatide and semaglutide demonstrated clinically meaningful weight reduction in people with obesity or overweight and type 2 diabetes (T2D) in SURMOUNT-2 and STEP 2 clinical trials, respectively. In the absence of head-to-head trials, this study compared the efficacy of tirzepatide 10 and 15 mg with semaglutide 2.4 mg using an indirect treatment comparison. MATERIALS AND

methodsMean percent change in weight from baseline, weight reduction ≥5% and mean change in glycated haemoglobin (HbA1c [%]) were compared between tirzepatide 10/15 mg (week 72, SURMOUNT-2) and semaglutide 2.4 mg (week 68, STEP 2) applying the Bucher method to the efficacy estimand. Sensitivity analyses included the use of matching-adjusted indirect comparison, treatment regimen estimand and comparing study outcomes at 68 weeks.

resultsTirzepatide 10 and 15 mg were associated with significantly greater mean percent weight reductions versus semaglutide (mean difference, 10 mg: 2.57%; 15 mg: 4.79%, p < 0.01). Tirzepatide 15 mg had significantly higher odds of achieving ≥5% weight reduction (odds ratio 15 mg: 1.76, 95% CI 1.04-2.97, p = 0.035; odds ratio 10 mg: 1.24, 95% CI 0.75-2.04, p = 0.407), and both tirzepatide doses were associated with significantly greater reductions in HbA1c (%) levels (mean difference, 10 mg: 0.47%; 15 mg: 0.56%, p < 0.001) than semaglutide. Sensitivity analyses were generally consistent with the primary analysis, exceptions including when power was reduced in the matching-adjusted indirect comparison analyses and in the categorical weight reduction outcome.

conclusionsThis analysis suggested greater reductions in bodyweight and HbA1c (%) levels associated with tirzepatide 10 and 15 mg than with semaglutide 2.4 mg in people with obesity or overweight and T2D.

Indexed as

Diabetes Mellitus, Type 2Glucagon-Like PeptidesHypoglycemic AgentsObesityOverweightTirzepatideAdultAgedFemaleGlucagon-Like Peptide 1Glycated HemoglobinHumansMaleMiddle AgedSemaglutideTreatment OutcomeGlucagon-Like Peptide 1Glucagon-Like PeptidesGlycated HemoglobinHypoglycemic AgentsSemaglutideTirzepatideindirect treatment comparisonobesitysemaglutidetirzepatidetype 2 diabetesweight reduction

Identifiers

PMID40321113
PMCPMC12146454

What Socratic holds

Texttitle and abstract
LicenceCC BY-NC-ND
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.