SynthesisEndocrinology, diabetes & metabolism2025

Tirzepatide Versus Semaglutide on Weight Loss in Type 2 Diabetes Patients: A Systematic Review and Meta-Analysis of Direct Comparative Studies.

Jimmy Wen, Burhaan Syed, Denise Nadora, Christiane How-Volkman, Ethan Bernstein, Alina Truong, Muzammil Akhtar, Adam Razick, Jose Puglisi, Eldo Frezza

Abstract readSystematic ReviewMeta-AnalysisComparative Study
In one paragraph

Synthesis in Endocrinology, diabetes & metabolism, 2025. The graph read 1 number from its abstract, feeding 1 cell of the map: it . Cited by 9 papers.

1number the graph read from it
1cell of the map it votes in
9citing 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.

← favours the treatmentfavours the comparator →
-6.210 · no effect
Weight losstirzepatide vs semaglutidefavours the treatment · t2d, obesityfeeds one cell of the map
Δ -4.84-6.21 to -3.47
The meta-analysis supports these findings with a mean difference of -4.84 kg (95% CI: -6.21 to -3.47), favouring tirzepatide.

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

No readable resultOpen 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 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

9 citing papers in PubMed.

  1. Review
  2. Review
  3. Article
  4. Article
  5. Article
  6. Review
  7. Review
  8. Review
  9. GLP-1 agonists and exercise: the future of lifestyle prioritization.Frontiers in clinical diabetes and healthcare · 2025
    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

10 authors.

Jimmy WenCalifornia Northstate University College of Medicine, Elk Grove, California, USA.ORCID 0009-0007-5412-8551
Burhaan SyedCalifornia Northstate University College of Medicine, Elk Grove, California, USA.
Denise NadoraCalifornia Northstate University College of Medicine, Elk Grove, California, USA.
Christiane How-VolkmanCalifornia Northstate University College of Medicine, Elk Grove, California, USA.
Ethan BernsteinCalifornia Northstate University College of Medicine, Elk Grove, California, USA.
Alina TruongCalifornia Northstate University College of Medicine, Elk Grove, California, USA.
Muzammil AkhtarCalifornia Northstate University College of Medicine, Elk Grove, California, USA.
Adam RazickUniversity of California, Los Angeles, Los Angeles, California, USA.
Jose PuglisiCalifornia Northstate University College of Medicine, Elk Grove, California, USA.
Eldo FrezzaCalifornia Northstate University College of Medicine, Elk Grove, California, USA.

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.

introductionGlucagon-like peptide-1 receptor agonists (GLP-1RAs) have emerged as an efficacious treatment for type 2 diabetes mellitus (T2DM) and have demonstrated substantial weight loss effects. This systematic review compares two prevalent GLP-1RAs, tirzepatide and semaglutide, with their weight loss effects and rates of adverse events (AEs).

methodsFollowing the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA), a systematic search was performed in PubMed, Embase and Cochrane Library for direct comparative studies between tirzepatide and semaglutide. A meta-analysis was conducted via a random-effects model to analyse the differences in weight loss outcomes between study cohorts.

resultsFour studies, with 28,827 patients (14,870 tirzepatide/13,928 semaglutide), mean age of 55.7 years (52.0 to 63.7) and mean follow-up of 35.9 weeks (23.6 to 44.6), were included in this study. Mean weight change across four studies for tirzepatide and semaglutide was -11.4% (-15.3% to -8.27%) and -7.3% (-8.3% to -6.08%), respectively. The meta-analysis supports these findings with a mean difference of -4.84 kg (95% CI: -6.21 to -3.47), favouring tirzepatide. The most common AEs were minor and moderate-severity gastrointestinal (GI) AEs.

conclusionCurrent literature supports tirzepatide demonstrating a higher impact on weight loss than semaglutide, with both demonstrating high rates of minimal- to moderate-severity AEs. Further research with comparative head-to-head trials will better elucidate these weight loss effects and safety profiles.

Indexed as

Diabetes Mellitus, Type 2Glucagon-Like PeptidesHypoglycemic AgentsTirzepatideWeight LossGlucagon-Like Peptide 1HumansSemaglutideGlucagon-Like Peptide 1Glucagon-Like PeptidesHypoglycemic AgentsSemaglutideTirzepatidediabetesmeta‐analysissemaglutidetirzepatideweight loss

Identifiers

PMID40184508
PMCPMC11970626

What Socratic holds

Texttitle and abstract
LicenceCC BY
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.