Article Text

Download PDFPDF

Efficacy and safety of sodium-glucose cotransporter 2 inhibitors (SGLT-2is) and glucagon-like peptide-1 receptor agonists (GLP-1RAs) in patients with type 2 diabetes: a systematic review and network meta-analysis study protocol
  1. Humaira Hussein1,2,
  2. Francesco Zaccardi2,
  3. Nafeesa N Dhalwani2,
  4. Melanie J Davies2,3,
  5. Kamlesh Khunti2,3,
  6. Laura J Gray1,2
  1. 1 Department of Health Sciences, University of Leicester, Leicester, UK
  2. 2 Diabetes Research Centre, Leicester General Hospital, Leicester, UK
  3. 3 NIHR Leicester Biomedical Research Centre, Leicester, UK
  1. Correspondence to Professor Laura J Gray; lg48{at}


Introduction Sodium-glucose cotransporter 2 inhibitors (SGLT-2is) and glucagon-like peptide-1 receptor agonists (GLP-1RAs) are two classes of glucose-lowering drugs gaining popularity in the treatment of type 2 diabetes mellitus (T2DM). Current guidelines suggest patient-centred approaches when deciding between available hyperglycaemia drugs with no indication to which specific drug should be administered. Despite systematic reviews and meta-analyses being conducted within SGLT-2is and GLP-1RAs, differences across these classes of drugs have not been investigated. Therefore, this systematic review and network meta-analysis (NMA) will aim to compare the efficacy and safety profiles across and within SGLT-2is and GLP-1RAs.

Methods PubMed, the Cochrane Central Register of Controlled Trials and ISI Web of Science will be searched from inception for published randomised controlled trials conducted in patients with T2DM, with at least two arms consisting of SGLT-2is, GLP-1RAs or control/placebo. Title and abstracts will be screened by two independent reviewers with conflicts resolved by a third. Data will be extracted by the primary researcher, a random sample will be checked by an independent reviewer. Risk of bias will be assessed using the Cochrane Risk of Bias Tool and overall quality of evidence will be assessed using the Grading of Recommendations Assessment, Development and Evaluation approach.

Study characteristics, participants baseline characteristics, mean change in cardiometabolic outcomes and number of adverse events will be extracted for each study. Primary outcome will be the mean change in glycated haemoglobin (HbA1c) (%, mmol/mol). Initial random-effects pairwise meta-analysis will be conducted for each unique treatment comparison where heterogeneity will be assessed. A Bayesian NMA approach will be adopted where random-effects generalised linear models will be fitted in WinBUGS. Sensitivity analysis will be conducted to assess choices of prior distributions and length of burn-in and sample.

Ethics and dissemination Ethics approval is not required for this study. Results from this study will be published in a peer-review journal.

PROSPERO registration number CRD42018091306.

  • glp-1ra
  • sglt-2i
  • type 2 diabetes mellitus
  • network meta-analysis

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:

Statistics from


  • Contributors Contributors to the conception, design and/or interpretation of this systematic review and network meta-analysis protocol: HH, LJG, KK, FZ, NND and MJD. Drafting and/or revising protocol for important content: HH, LJG, KK, FZ, NND and MJD. Approving the final version of the protocol: HH, LJG, KK, FZ, NND and MJD. Accountability of all aspects of the work: HH, LJG, KK, FZ, NND and MJD.

  • Funding This report is the independent research of HH supported by the National Institute of Health Research Collaborations for Leadership in Applied Health Research and Care–East Midlands (NIHR CLAHRC–EM) as part of a PhD project. FZ is a Clinical Research Fellow supported by the NIHR CLAHRC–EM.

  • Competing interests None declared.

  • Patient consent Not required.

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

Request Permissions

If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.