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Clinical Research

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

International Journal of Obesity volume 47, pages 883–892 (2023)Cite this article

Subjects

Abstract

Objectives

Tirzepatide 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.

Methods

We 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.

Results

Of 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.

Conclusions

The 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.

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Fig. 1: PRISMA flow diagram of study screening and selection.
Fig. 2: Comparison of tirzepatide versus placebo for absolute and percent weight change.
Fig. 3: Comparison of tirzepatide versus placebo for BMI and waist circumference change.
Fig. 4

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Data availability

This meta-analysis is based on data extracted from previously published research that belongs to the public domain. The authors do not have access to individual study’s patient-level data, and encourage readers interested in these types of data to contact the corresponding author from each of the studies here included.

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Funding

Funding

No funding source was involved in the data collection, statistical analyses, and writing of the paper. FM is supported by a T32-postdoctoral Training Grant in Cardiovascular Research from the National Heart, Lung, and Blood Institute (T32 HL007604).

Author information

Author notes

  1. These authors contributed equally: Filipe Azevedo Moura, Vladimir Vitalievich Rafalskiy.

Authors and Affiliations

  1. Division of Medicine, Federal University of Rio de Janeiro, Macaé, Rio de Janeiro, Brazil

    Yasmin Luz Lima de Mesquita

  2. Division of Medicine, Immanuel Kant Baltic Federal University, Kaliningrad, Kaliningrad Oblast, Russia

    Izabela Pera Calvi, Sara Almeida Cruz & Vladimir Vitalievich Rafalskiy

  3. Division of Medicine, Universitat Internacional de Catalunya, Barcelona, Catalunya, Spain

    Isabela Reis Marques

  4. Division of Pulmonary and Critical Care, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA

    Eduardo Messias Hirano Padrao

  5. Division of Medicine, Federal University of Minas Gerais, Belo Horizonte, Minas Gerais, Brazil

    Pedro Emanuel de Paula Carvalho

  6. Division of Medicine, Federal University of Rio Grande do Norte, Natal, Rio Grande do Norte, Brazil

    Caroliny Hellen Azevedo da Silva

  7. Division of Cardiovascular Medicine, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA, USA

    Rhanderson Cardoso & Filipe Azevedo Moura

  8. TIMI study group, Division of Cardiovascular Medicine, Brigham and Women’s Hospital, Harvard Medical School, Boston MA, USA

    Filipe Azevedo Moura

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Contributions

YM conceived and designed the study. YM and CS designed the review protocol and participated in the database searches and screening process. YM extracted data and performed all statistical analyses. YM, IC, IM, and SC, interpreted the results of the analysis. EP created the TSA. PC did the leave-one-out sensitivity analysis, Baujat plot and the meta-regressions. YM wrote the initial draft of the manuscript, which was then edited by IC, IM, SC, EP, PC, CS, and FM. Feedback was given by FM, RC, and VR on the final draft. All authors read and approved the final manuscript. All authors agree to be accountable for all aspects of the work. YM is the guarantor of this work and, as such, had full access to all the data in the study and takes responsibility for its accuracy and integrity.

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Correspondence to Yasmin Luz Lima de Mesquita.

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de Mesquita, Y.L.L., Pera Calvi, I., Reis Marques, I. et al. Efficacy and safety of the dual GIP and GLP-1 receptor agonist tirzepatide for weight loss: a meta-analysis of randomized controlled trials. Int J Obes 47, 883–892 (2023). https://doi.org/10.1038/s41366-023-01337-x

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