SynthesisInternational journal of obesity (2005)2023

Efficacy and safety of the dual GIP and GLP-1 receptor agonist tirzepatide for weight loss: a meta-analysis of randomized controlled trials.

Yasmin Luz Lima de Mesquita, Izabela Pera Calvi, Isabela Reis Marques, Sara Almeida Cruz, Eduardo Messias Hirano Padrao, Pedro Emanuel de Paula Carvalho, Caroliny Hellen Azevedo da Silva, Rhanderson Cardoso, Filipe Azevedo Moura, Vladimir Vitalievich Rafalskiy

Abstract readMeta-AnalysisReview
PubMed Publisher
In one paragraph

Synthesis in International journal of obesity (2005), 2023. The graph read 4 numbers from its abstract, feeding 2 cells of the map: it supports the treatment in 2. Cited by 27 papers, 5 of them syntheses that pooled it.

4numbers the graph read from it
2cells of the map it votes in
27citing papers in PubMed, 5 pooled it
10.1field-weighted citation impact, top 1% of its field
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.

Ratios

← favours the treatmentfavours the comparator →
24101 · no effect
Adverse events & safetyfavours the comparator · against placebo · t2d, obesityfeeds one cell of the map
OR 7.004.30 to 11.4p < 0.001
Adverse events were more common with tirzepatide with respect to nausea (OR 4.2; 95% CI 2.4, 7.5; p < 0.001), vomiting (OR 7.0; 95% CI 4.3, 11.4; p < 0.001), and diarrhea (OR 2.8; 95% CI 1.6, 4.9; p < 0.001) (15 mg dose), when compared with placebo.
Adverse events & safetyfavours the comparator · against placebo · t2d, obesityfeeds one cell of the map
OR 4.202.40 to 7.50p < 0.001
Adverse events were more common with tirzepatide with respect to nausea (OR 4.2; 95% CI 2.4, 7.5; p < 0.001), vomiting (OR 7.0; 95% CI 4.3, 11.4; p < 0.001), and diarrhea (OR 2.8; 95% CI 1.6, 4.9; p < 0.001) (15 mg dose), when compared with placebo.
Adverse events & safetyfavours the comparator · against placebo · t2d, obesityfeeds one cell of the map
OR 2.801.60 to 4.90p < 0.001
Adverse events were more common with tirzepatide with respect to nausea (OR 4.2; 95% CI 2.4, 7.5; p < 0.001), vomiting (OR 7.0; 95% CI 4.3, 11.4; p < 0.001), and diarrhea (OR 2.8; 95% CI 1.6, 4.9; p < 0.001) (15 mg dose), when compared with placebo.

Differences

← favours the treatmentfavours the comparator →
-11.00 · no effect
Body weight & compositionfavours the treatment · against placebo · t2d, obesityfeeds one cell of the map
change -8.10-11.0 to -5.20p < 0.001
Pooled analysis showed that tirzepatide 5 mg, 10 mg, and 15 mg were more effective than placebo, with MD in body weight of -7.7 kg (95% CI -11.0, -4.4; p < 0.001), -11.6 kg (95% CI -18.8, -4.3; p = 0.002), and -11.8 kg (95% CI -17.4, -6.2; p < 0.001), respectively, and MD in percent change in weight of -8.1% (95% CI -11.0, -5.2; p < 0.001), -11.9% (95% CI -18.1, -5.6; p < 0.001), and -12.4% (95% CI -17.2, -7.5; p < 0.001), respectively.

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×adverse events & safety

SupportsOpen on the map →What to test next →

4 readable studies in this cell: 2 favour the treatment, 2 find no difference, 0 favour the comparator.

Belief with this paper
0.00contested · 0 families support, 3 contradict · against placebo
Without itNot a counted family in this claim, so removing it changes nothing.
← favours the treatmentfavours the comparator →
0 · no effect
NCT0498257592 enrolled · 2021
Δ -0.30-0.79 to 0.19
NCT0408133755 enrolled · 2020
Δ -0.03-0.05 to -0.02
NCT0405055342 enrolled · 2020
Δ -0.89-4.10 to 2.33

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

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 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

27 citing papers in PubMed, 5 syntheses or guidelines pooled it, 50 citations in OpenAlex.

  1. Guideline
  2. Efficacy and Safety of Tirzepatide on Weight Loss in Patients Without Diabetes Mellitus: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.Obesity reviews : an official journal of the International Association for the Study of Obesity · 2025 · on this map
    Pooled it
  3. Pooled it
  4. Pooled it
  5. Pooled it
  6. Review
  7. Review
  8. Article
  9. Article
  10. Article
  11. Article
  12. Review
  13. Article
  14. Review
  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

10 authors at 7 institutions in 4 countries.

Yasmin Luz Lima de MesquitaDivision of Medicine, Federal University of Rio de Janeiro, Macaé, Rio de Janeiro, Brazil. mesquita.ll.yasmin@ufrj.br.ORCID 0000-0001-8607-6302
Izabela Pera CalviDivision of Medicine, Immanuel Kant Baltic Federal University, Kaliningrad, Kaliningrad Oblast, Russia.ORCID 0000-0002-5448-8190
Isabela Reis MarquesDivision of Medicine, Universitat Internacional de Catalunya, Barcelona, Catalunya, Spain.ORCID 0000-0002-5160-0650
Sara Almeida CruzDivision of Medicine, Immanuel Kant Baltic Federal University, Kaliningrad, Kaliningrad Oblast, Russia.ORCID 0000-0003-2814-9627
Eduardo Messias Hirano PadraoDivision of Pulmonary and Critical Care, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.ORCID 0000-0001-5323-7579
Pedro Emanuel de Paula CarvalhoDivision of Medicine, Federal University of Minas Gerais, Belo Horizonte, Minas Gerais, Brazil.ORCID 0000-0002-0918-6759
Caroliny Hellen Azevedo da SilvaDivision of Medicine, Federal University of Rio Grande do Norte, Natal, Rio Grande do Norte, Brazil.
Rhanderson CardosoDivision of Cardiovascular Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.ORCID 0000-0003-3622-7605
Filipe Azevedo Moura *Division of Cardiovascular Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.ORCID 0000-0001-8017-1675
Vladimir Vitalievich Rafalskiy *Division of Medicine, Immanuel Kant Baltic Federal University, Kaliningrad, Kaliningrad Oblast, Russia.
Immanuel Kant Baltic Federal University · RUBrigham and Women's Hospital · USHarvard University · USUniversidade Federal de Minas Gerais · BRUniversidade Federal do Rio de Janeiro · BRUniversidade Federal do Rio Grande do Norte · BRUniversitat Internacional de Catalunya · ES

Funding

TRAINING PROGRAM IN CARDIOVASCULAR RESEARCHT32HL007604 · BRIGHAM AND WOMEN'S HOSPITAL · 1985 to 2025
$4.2M
NHLBI NIH HHS T32 HL007604
8 · The paper itself

Abstract

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

objectivesTirzepatide is a dual glucose-dependent insulinotropic polypeptide and glucagon-like peptide-1 receptor agonist approved for type 2 diabetes. We performed a meta-analysis to assess tirzepatide's weight reduction efficacy and safety.

methodsWe searched PubMed, Embase, and Cochrane for randomized controlled trials published from inception to July 2022, comparing tirzepatide with placebo for the co-primary endpoints of absolute and percent change in weight. Mean difference (MD) and odds ratio (OR) were calculated for continuous and binary outcomes, respectively. Review Manager 5.4.1 and RStudio were used for the statistical analysis, and RoB-2 (Cochrane) to assess the risk of bias.

resultsOf 397 search results, 6 studies (4036 participants) ranging from 12 to 72 weeks were included. Pooled analysis showed that tirzepatide 5 mg, 10 mg, and 15 mg were more effective than placebo, with MD in body weight of -7.7 kg (95% CI -11.0, -4.4; p < 0.001), -11.6 kg (95% CI -18.8, -4.3; p = 0.002), and -11.8 kg (95% CI -17.4, -6.2; p < 0.001), respectively, and MD in percent change in weight of -8.1% (95% CI -11.0, -5.2; p < 0.001), -11.9% (95% CI -18.1, -5.6; p < 0.001), and -12.4% (95% CI -17.2, -7.5; p < 0.001), respectively. Tirzepatide also reduced BMI and waist circumference. Adverse events were more common with tirzepatide with respect to nausea (OR 4.2; 95% CI 2.4, 7.5; p < 0.001), vomiting (OR 7.0; 95% CI 4.3, 11.4; p < 0.001), and diarrhea (OR 2.8; 95% CI 1.6, 4.9; p < 0.001) (15 mg dose), when compared with placebo.

conclusionsThe results support that tirzepatide leads to substantial weight reduction and constitutes a valuable therapeutic option for weight management, despite an increase in gastrointestinal symptoms. PROTOCOL REGISTRATION: CRD42022348576.

Indexed as

Diabetes Mellitus, Type 2Gastric Inhibitory PolypeptideGlucagon-Like Peptide-1 Receptor AgonistsHumansHypoglycemic AgentsRandomized Controlled Trials as TopicTirzepatideWeight LossGastric Inhibitory PolypeptideGlucagon-Like Peptide-1 Receptor AgonistsHypoglycemic AgentsTirzepatide

Identifiers

PMID37460681
OpenAlexW4384521950

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.