Beyond SGLT2: Exploring the Therapeutic Potential of Lesser-Known SGLT Isoform Inhibitors

This paper presents a review of studies on SGLT protein inhibitors, based on literature published between 2000 and 2025, sourced from the Scopus, ScienceDirect, Google Scholar and PubMed databases. The individual isoforms of SGLT proteins are briefly described, with attention to their distribution in the body and biological functions. Representative inhibitors and their potential biological effects are also discussed. Beyond the well-established glucose-lowering properties, characteristic of the extensively studied SGLT2 inhibitors, this review explores additional effects, including anticancer, anti-inflammatory, antioxidant, and neuroprotective activities. The analysis encompasses synthetic SGLT inhibitors, computer-designed molecules, and a wide range of naturally derived compounds, including medicinal plants and food-based substances. Importantly, the review deliberately excludes SGLT2 inhibitors, such as the well-known gliflozin class due to the abundance of existing reviews focused specifically on them. This review focuses on potential inhibitors of the SGLT1, SGLT3, SGLT4, SGLT5, and SGLT6 isoforms, emphasizing their diverse physiological roles beyond diabetes and cardiovascular disease, including applications in cancer therapy and neuroprotection. Particular attention is given to the SGLT1 isoform, for which numerous synthetic inhibitors with promising therapeutic potential have been identified. Additionally, natural compounds, especially those derived from medicinal plants and dietary sources, are extensively documented for their inhibitory effects. For the remaining isoforms (SGLT3–SGLT6), all available data on selective inhibitors were examined, alongside an evaluation of their possible therapeutic applications in light of current scientific knowledge.