Calibrating a network meta-analysis of diabetes trials of sodium glucose cotransporter 2 inhibitors, glucagon-like peptide-1 receptor analogues and dipeptidyl peptidase-4 inhibitors to a representative routine population: a systematic review protocol.

Participants in randomised controlled trials (trials) are generally younger and healthier than many individuals encountered in clinical practice. Consequently, the applicability of trial findings is often uncertain. To address this, results from trials can be calibrated to more representative data sources. In a network meta-analysis, using a novel approach which allows the inclusion of trials whether or not individual-level participant data (IPD) is available, we will calibrate trials for three drug classes (sodium glucose cotransporter 2 (SGLT2) inhibitors, glucagon-like peptide-1 (GLP1) receptor analogues and dipeptidyl peptidase-4 (DPP4) inhibitors) to the Scottish diabetes register. Medline and EMBASE databases, the US clinical trials registry (clinicaltrials.gov) and the Chinese Clinical Trial Registry (chictr.org.cn) will be searched from 1 January 2002. Two independent reviewers will apply eligibility criteria to identify trials for inclusion. Included trials will be phase 3 or 4 trials of SGLT2 inhibitors, GLP1 receptor analogues or DPP4 inhibitors, with placebo or active comparators, in participants with type 2 diabetes, with at least one of glycaemic control, change in body weight or major adverse cardiovascular event as outcomes. Unregistered trials will be excluded.We have identified a target population from the population-based Scottish diabetes register. The chosen cohort comprises people in Scotland with type 2 diabetes who either (1) require further treatment due to poor glycaemic control where any of the three drug classes may be suitable, or (2) who have adequate glycaemic control but are already on one of the three drug classes of interest or insulin. Ethical approval for IPD use was obtained from the University of Glasgow MVLS College Ethics Committee (Project: 200160070). The Scottish diabetes register has approval from the Scottish A Research Ethics Committee (11/AL/0225) and operates with Public Benefit and Privacy Panel for Health and Social Care approval (1617-0147). CRD42020184174.

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Competing interests: DMcA, EB, DP, SD, NW report funding for the present manuscript from the Medical Research Council (MRC) (MR/T017112/1). DMcA reports funding from the Wellcome Trust. PH reports funding from the MRC. AA reports departmental support for a randomized controlled trial from NovoNordisk to look at a GLP-agonist in a disease area other than diabetes. LB reports investment funds with shares held in various companies including Novo Nordisk and Astrazeneca, however these are chosen at the discretion of the fund manager and will fluctuate over time. No stocks/funds were chosen to benefit specifically from any company with a relationship to this manuscript. JP reports institutional grants via Merck KGaA and Novo Nordisk (co-fund with JDRF), institutional supply of investigational medicinal product for clinical trials from AstraZeneca, and personal fees from Boehringer Ingelheim (via IQVIA and via ACI Clinical), Biocon, Novo Nordisk and Merck. JP is also a member of an advisory board for Novo Nordisk and has an unpaid leadership role for Novo Nordisk UK Research Foundation (former Chair of Board of Trustees). NS reports institutional grants from AstraZeneca, Boehringer Ingelheim, Novartis and Roche Diagnostics and personal fees from Abbott Laboratories, Afimmune, Amgen, AstraZeneca, Boehringer Ingelheim, Eli Lilly, Hanmi Pharmaceuticals, Janssen, Merck Sharp & Dohme, Novartis, Novo Nordisk, Pfizer, and Sanofi. LT reports MRC, Wellcome and NIHR funding, funding from GSK for an epidemiological study of kidney disease (no personal payment received) and reports consulting for Bayer in relation to an observational study of chronic kidney disease (no personal payment received). LT is also a member of the MHRA Expert advisory group (Women’s Health) and a member of 3 non-industry funded (NIHR/MRC) trial advisory committees (unpaid). NW reports honoraria for training and masterclasses on statistical methodology from Association of British Pharmaceutical Industries, Campbell Ireland, Centre for Global Development, NICE International and NICE Scientific Advice. All other authors report no competing interests.