A registry-based randomised trial comparing an SGLT2 inhibitor and metformin as standard treatment of early stage type 2 diabetes (SMARTEST): Rationale, design and protocol
Johan Sundström, Robin Kristófi, Ollie Östlund, Louise Bennet, Björn Eliasson, Stefan Jansson, Janeth Leksell, Kristina Almby, Martin Lundqvist, Jan W Eriksson, SMARTEST study group (see list in Appendix), Johan Sundström, Robin Kristófi, Ollie Östlund, Louise Bennet, Björn Eliasson, Stefan Jansson, Janeth Leksell, Kristina Almby, Martin Lundqvist, Jan W Eriksson, SMARTEST study group (see list in Appendix)
Abstract
Aim: SGLT2 inhibitors have been shown to reduce cardiovascular and renal complications in type 2 diabetes (T2D) patients at high cardiovascular risk. Metformin is currently widely used as initial monotherapy in T2D but lacks convincing data to show that it reduces risk of complications. We aim to compare the SGLT2 inhibitor dapagliflozin and metformin as first-line T2D medication with regard to development of complications in a registry-based randomised controlled trial.
Methods: The SGLT2 inhibitor or metformin as standard treatment of early stage type 2 diabetes (SMARTEST) trial will enrol 4300 subjects at 30-40 study sites in Sweden who will be randomised 1:1 to either metformin or dapagliflozin. Participants must have T2D duration <4 years, no prior cardiovascular disease, and be either drug-naïve or on monotherapy for T2D.
Results: The primary endpoint is a composite of all-cause death, major adverse cardiovascular events and occurrence or progression of microvascular complications (retinopathy, nephropathy, diabetic foot lesions). Secondary endpoints include individual components of the primary endpoint, start of insulin therapy, risk factor biomarkers, patient-reported outcome measures, and cost-effectiveness analysis. Outcomes will primarily be assessed using nationwide healthcare registries.
Conclusions: The SMARTEST trial will investigate whether dapagliflozin is superior to metformin in preventing complications in early stage T2D. (Clinicaltrials.gov identifier NCT03982381, EudraCT 2019-001046-17).
Keywords: Diabetes complications; Metformin; Registry-based randomised controlled trials; SGLT2 inhibitors; Type 2 diabetes.
Copyright © 2021 The Author(s). Published by Elsevier Inc. All rights reserved.
Source: PubMed