Therapeutic Repositioning of SGLT2 Inhibitors Using Real-World Data: A Scoping Review of Emerging Indications and Rare Diseases
Abstract
Abstract Background and Aims Sodium-glucose cotransporter-2 inhibitors (SGLT2i), initially approved for type 2 diabetes mellitus, have progressively emerged as cardio-renal protective agents. Beyond glycaemic control, evidence indicates that SGLT2i act as systemic endocrine-metabolic modulators, via pleiotropic mechanisms including NLRP3 inflammasome inhibition, ketone-driven metabolic reprogramming, HIF-2α-mediated erythropoietic effects, and uricosuric transporter activity. This scoping review maps Real-World Data (RWD)-based evidence on SGLT2i repositioning across these pathways and rare diseases. Methods A systematic search was conducted on PubMed and Scopus from inception to 31 May 2026, following PRISMA-ScR guidelines (OSF registration: 10.17605/OSF.IO/794CX). Eligibility followed a PCC framework (Population: any age/comorbidity; Concept: pleiotropic or off-label SGLT2i effects beyond approved cardio-renal indications; Context: real-world studies). Original peer-reviewed studies using RWD, including cohort studies and case series for rare diseases, were included. Methodological quality was assessed using the Newcastle-Ottawa Scale (NOS) and the Murad et al. tool. Due to clinical and methodological heterogeneity, a narrative synthesis was performed. Results Seventy-four studies (2017–2026) were included, 66% published in 2024–2026. Research was concentrated in Asia (27 studies, NHIRD-based) and North America (24 studies, mainly EHR/TriNetX-based), with Europe…
How strong is the evidence?
Evidence Hub reads this as a case series, done in people. Its evidence level is 5 of 5 (Very low · case / narrative / animal / in vitro / in silico). Case reports, narrative reviews, and animal, cell or computer-model studies give the weakest evidence for human health. Reported size: 21 participants or records.
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