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  • Glucagon-like peptide 1 agonists for treatment of patients with type 2 diabetes who fail metformin monotherapy: systematic review and meta-analysis of economic evaluation studies

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Epidemiology/Health Services Research
Glucagon-like peptide 1 agonists for treatment of patients with type 2 diabetes who fail metformin monotherapy: systematic review and meta-analysis of economic evaluation studies
  1. Bhavani Shankara Bagepally1,2,
  2. Usa Chaikledkaew2,3,
  3. Yogesh Krishnarao Gurav2,4,
  4. Thunyarat Anothaisintawee2,5,
  5. Sitaporn Youngkong2,3,
  6. Nathorn Chaiyakunapruk6,
  7. Mark McEvoy7,
  8. John Attia7,8,
  9. Ammarin Thakkinstian2,9
  1. 1Non-Communicable Diseases, ICMR-National Institute of Epidemiology, Chennai, India
  2. 2Mahidol University Health Technology Assessment (MUHTA) Graduate Program, Mahidol University, Bangkok, Thailand
  3. 3Social and Administrative Pharmacy Division, Department of Pharmacy, Faculty of Pharmacy, Mahidol University, Bangkok, Thailand
  4. 4Epidemiology Group, ICMR-National Institute of Virology, Pune, India
  5. 5Department of Family Medicine, Faculty of Medicine Ramathibodi Hospital, Mahidol University, Bangkok, Thailand
  6. 6College of Pharmacy, University of Utah, Salt Lake City, Utah, USA
  7. 7Centre for Clinical Epidemiology and Biostatistics, Hunter Medical Research Institute, School of Medicine and Public Health, University of Newcastle, New Lambton, New South Wales, Australia
  8. 8Division of Medicine, John Hunter Hospital, New Lambton, New South Wales, Australia
  9. 9Department of Clinical Epidemiology and Biostatistics, Faculty of Medicine Ramathibodi Hospital, Mahidol University, Bangkok, Thailand
  1. Correspondence to Dr Usa Chaikledkaew; usa.chi{at}mahidol.ac.th

Abstract

Objectives To conduct a systematic review and meta-analysis and to pool the incremental net benefits (INBs) of glucagon-like peptide 1 (GLP1) compared with other therapies in type 2 diabetes mellitus (T2DM) after metformin monotherapy failure.

Research design and methods The study design is a systematic review and meta-analysis. We searched MEDLINE (via PubMed), Scopus and Tufts Registry for eligible cost–utility studies up to June 2018, adhering to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guideline. We conducted a systematic review and pooled the INBs of GLP1s compared with other therapies in T2DM after metformin monotherapy failure. Various monetary units were converted to purchasing power parity, adjusted to 2017 US$. The INBs were calculated and then pooled across studies, stratified by level of country income; a random-effects model was used if heterogeneity was present, and a fixed-effects model if it was absent. Heterogeneity was assessed using Q test and I2 statistic.

Results A total of 56 studies were eligible, mainly from high-income countries (HICs). The pooled INBs of GLP1s compared with dipeptidyl peptidase-4 inhibitor (DPP4i) (n=10), sulfonylureas (n=6), thiazolidinedione (TZD) (n=3), and insulin (n=23) from HICs were US$4012.21 (95% CI US$−571.43 to US$8595.84, I2=0%), US$3857.34 (95% CI US$−7293.93 to US$15 008.61, I2=45.9%), US$37 577.74 (95% CI US$−649.02 to US$75 804.50, I2=92.4%) and US$14 062.42 (95% CI US$8168.69 to US$19 956.15, I2=86.4%), respectively. GLP1s were statistically significantly cost-effective compared with insulins, but not compared with DPP4i, sulfonylureas, and TZDs. Among GLP1s, liraglutide was more cost-effective compared with lixisenatide, but not compared with exenatide, with corresponding pooled INBs of US$4555.09 (95% CI US$3992.60 to US$5117.59, I2=0) and US$728.46 (95% CI US$−1436.14 to US$2893.07, I2=0), respectively.

Conclusion GLP1 agonists are a cost-effective choice compared with insulins, but not compared with DPP4i, sulfonylureas and TZDs.

PROSPERO registration number CRD42018105193.

  • Glucagon-Like Peptide-1 (GLP-1)
  • economic analysis
  • cost-effectiveness
  • meta-analysis
https://creativecommons.org/licenses/by/4.0/

This is an open access article distributed in accordance with the Creative Commons Attribution 4.0 Unported (CC BY 4.0) license, which permits others to copy, redistribute, remix, transform and build upon this work for any purpose, provided the original work is properly cited, a link to the licence is given, and indication of whether changes were made. See: https://creativecommons.org/licenses/by/4.0/.

https://doi.org/10.1136/bmjdrc-2019-001020

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    Footnotes

    • Contributors BSB performed data extraction, meta-analysis, data interpretation and wrote the manuscript. UC designed and supervised meta-analysis, checked data accuracy, and assisted in writing and revising the manuscript. YKG performed data extraction and meta-analysis and wrote the manuscript. TA and SY assisted in supervising the meta-analysis and writing the manuscript. MMcE, NC, and JA contributed to data interpretation, as well as writing and revising the manuscript. AT designed and supervised meta-analysis, checked data accuracy and assisted in writing and revising the manuscript. All authors reviewed and approved the revised manuscript.

    • Funding This work is a part of training in Health Technology Assessment's master’s degree, in which scholarship is provided by Mahidol University and the International Decision Support Initiative (iDSI). This work was produced as part of the International Decision Support Initiative (www.idsihealth.org), which supports countries to get the best value for money from health spending. iDSI receives funding support from the Bill and Melinda Gates Foundation, the UK Department for International Development, and the Rockefeller Foundation.

    • Disclaimer The findings, interpretations and conclusions expressed in this article do not necessarily reflect the views of the aforementioned funding agencies.

    • 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. All the primary data were collected from published journals and reported in the manuscript.