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Metabolism
Effect of incretin-based therapies on cancers of digestive system among 101 595 patients with type 2 diabetes mellitus: a systematic review and network meta-analysis combining 84 trials with a median duration of 30 weeks
  1. Sanbao Chai1,
  2. Shuqing Yu2,
  3. Zhirong Yang3,
  4. Shanshan Wu4,
  5. Le Gao2,
  6. Haining Wang5,
  7. Yuan Zhang6,
  8. Siyan Zhan2,
  9. Linong Ji7,
  10. Feng Sun2
  1. 1Department of Endocrinology and Metabolism, Peking University International Hospital, Beijing, China
  2. 2Department of Epidemiology and Biostatistics, School of Public Health, Peking University Health Science Centre, Beijing, China
  3. 3Primary Care Unit, School of Clinical Medicine, University of Cambridge, Cambridge, UK
  4. 4National Clinical Research Center of Digestive Disease, Beijing Friendship Hospital Affiliated to Capital Medical University, Beijing, China
  5. 5Department of Endocrinology and Metabolism, Peking University Third Hospital, Beijing, China
  6. 6Department of Clinical Epidemiology and Biostatistics, McMaster University, Hamilton, Ontario, Canada
  7. 7Department of Endocrinology and Metabolism, Peking University People’s Hospital, Beijing, China
  1. Correspondence to Professor Feng Sun; sunfeng{at}bjmu.edu.cn; Professor Linong Ji; jiln{at}bjmu.edu.cn

Abstract

Objectives To evaluate the risk of cancers of digestive system with incretin-based therapies among patients with type 2 diabetes mellitus.

Research design and methods Medline, Embase, Cochrane Library and ClinicalTrials.gov databases were searched for randomized controlled clinical trials that compared incretin-based drugs with placebo or other antidiabetic drugs. Paired reviewers independently screened citations, extracted data and assessed risk of bias of included studies. Network meta-analysis was performed, followed by subgroup analysis. The Grading of Recommendations Assessment, Development and Evaluation system was used to assess the quality of evidence.

Results A total of 84 studies (n=101 595) involving cancers of digestive system were identified (a median follow-up of 30 weeks). The risk of cancers of digestive system with incretin-based therapies was comparable with insulin (OR: 0.86, 95% CI 0.27 to 2.69), metformin (OR: 0.32, 95% CI 0.07 to 1.38), sodium-glucose co-transporter 2 (OR: 5.26, 95% CI 0.58 to 47.41), sulfonylureas (OR: 1.27, 95% CI 0.68 to 2.39), thiazolidinediones (OR: 0.42, 95% CI 0.13 to 1.42), alpha-glucosidase inhibitors (OR: 2.98, 95% CI 0.12 to 73.80), and placebo (OR: 0.87, 95% CI 0.71 to 1.05). The results of subgroup analysis based on the type of digestive system cancers indicated that incretin-based therapies did not increase the risk of gastrointestinal cancers, respectively. The results of subgroup analysis based on age, duration, mean HbA1c, trial duration, and sample size did not indicate the risk of digestive system cancers.

Conclusions Moderate to high Grading of Recommendations Assessment, Development and Evaluation evidence suggests that incretin-based therapies were not associated with an increased risk of cancer of digestive system in patients with type 2 diabetes mellitus.

  • incretin
  • digestive system
  • cancer
  • meta-analysis
  • type 2 diabetes

This is an open access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited, appropriate credit is given, any changes made indicated, and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/.

https://doi.org/10.1136/bmjdrc-2019-000728

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    Footnotes

    • Contributors FS and LJ designed the study. SZ and HW gave guidance to this work. SBC and SY retrieved the document. SBC, SY, ZY, SW, LG, and YZ built databases and extracted data. SY input data and conducted statistical analysis. SBC wrote the manuscript.

    • Funding This work was supported by the National Natural Science Foundation of China (81302508, 71673003).

    • Competing interests None declared.

    • Patient consent for publication Not required.

    • Provenance and peer review Not commissioned; externally peer reviewed.

    • Data availability statement All data relevant to the study are included in the article or uploaded as supplementary information.