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Safety and efficacy of GLP-1 and glucagon receptor dual agonist for the treatment of type 2 diabetes and obesity: a systematic review and meta-analysis of randomized controlled trials

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Abstract

Purpose

This study aimed to investigate the effects of randomized, placebo-controlled trials involving the GLP-1 and glucagon receptor dual agonists, mazdutide, and cotadutide, on glycaemic control and body weight changes in individuals with type 2 diabetes mellitus (T2DM), obesity, or both.

Methods

We conducted searches in Medline, PubMed, Scopus, the Cochrane database, and Web of Science up to March 5, 2024. The primary outcomes assessed were changes in HbA1c level and percentage changes in body weight from baseline (CFB).

Results

Eleven studies and four unpublished trials were included. The pooled meta-analysis revealed a significant reduction in HbA1c (MD = −0.63%; 95% CI = [−0.82, −0.44]; P < 0.00001), fasting plasma glucose (MD = −1.71 mmol/L; 95% CI = [−2.31, −1.10]; P < 0.00001), and percentage change in body weight (MD = −4.16%; 95% CI = [−5.41, −2.92]; P < 0.00001). Safety analysis revealed no significant change in serious adverse events (OR = 1.03; 95% CI = [0.61, 1.75]; P = 0.91), but there were significantly higher odds of treatment-emergent adverse events (OR = 2.52; 95% CI = [1.92, 3.30]; P < 0.00001) and vomiting (OR = 6.05; 95% CI = [3.52, 10.40]; P < 0.00001).

Conclusion

These results suggest that mazdutide and cotadutide are effective for glycaemic control and weight reduction in individuals with T2DM, obesity, or both.

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Funding

This work was supported by the National Key R&D Program of China (2021YFC2701700, 2021YFC2701704); National Natural Science Foundation of China (81971433, 82271749, 82201905); the Fundamental Research Funds for the Central University (SCU2023D006); Clinical research Special Fund of Wu Jieping Medical Foundation (320.6750.2023-24-4).

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Author notes

  1. These authors contributed equally: Bixin Deng, Tiechao Ruan

Authors and Affiliations

  1. Department of Pediatrics, West China Second University Hospital, Sichuan University, Chengdu, China

    Bixin Deng, Tiechao Ruan, Junjie Ying, Shiping Li, Ruixi Zhou & Dezhi Mu

  2. Key Laboratory of Birth Defects and Related Diseases of Women and Children (Sichuan University), Ministry of Education, NHC Key Laboratory of Chronobiology, Sichuan University, Chengdu, China

    Bixin Deng, Tiechao Ruan, Junjie Ying, Shiping Li, Ruixi Zhou & Dezhi Mu

  3. Integrated Care Management Center, West China Hospital, Sichuan University, Chengdu, China

    Wenting Lu

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  1. Bixin Deng
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Contributions

B.D. and T.R. conceived the study; B.D. and T.R. made the literature search; T.R. and W.L. extracted and analyzed the data; B.D. wrote the draft; T.R., W.L., J.Y. and R.Z. reviewed the article; S.P. and D.M. supervised the study; R.Z. and D.M. are the project managers. All authors approved the final version of the article.

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Correspondence to Ruixi Zhou or Dezhi Mu.

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Deng, B., Ruan, T., Lu, W. et al. Safety and efficacy of GLP-1 and glucagon receptor dual agonist for the treatment of type 2 diabetes and obesity: a systematic review and meta-analysis of randomized controlled trials. Endocrine (2024). https://doi.org/10.1007/s12020-024-03857-6

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