What is it about?
Diabetes is a long-term condition in which sugar builds up in the blood because the body doesn’t make enough insulin or can’t use it well. Over time, high blood sugar can damage the heart, kidneys, eyes, and nerves. Normally, the kidneys filter sugar out of the blood and then take almost all of it back. Gliflozins (SGLT-2 inhibitors) are medicines that block this “take-back” step, so extra sugar leaves the body in urine. This lowers blood sugar without relying on insulin and often helps with weight loss and blood pressure. This article reviews how these medicines are built and how they work, focusing on bexagliflozin, approved by the US FDA in 2023. An early sugar-blocking compound from apple tree bark, phlorizin, broke down too easily in the body. Modern gliflozins use a sturdier chemical bond, which helps them last long enough to work. Computer-based predictions suggest bexagliflozin is well absorbed as a tablet and suits once-daily use. The article also summarizes clinical trials. In adults with type 2 diabetes, bexagliflozin lowered blood sugar, helped with weight loss, and modestly reduced blood pressure. It worked about as well as the other diabetes medicines it was compared with, including in people with mild-to-moderate kidney disease. The most common side effects were urinary and genital infections, which are expected because sugar in urine can encourage germs to grow. The article also covers possible drug interactions and early research into newer versions that may help the heart, kidneys, and liver. Take-home message: Bexagliflozin is a promising once-daily tablet that helps the kidneys remove extra sugar, with benefits beyond blood sugar control. Its long-term effects on heart and kidney health still need more study.
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Why is it important?
Diabetes now affects about 422 million people worldwide, and gliflozins are among the fastest-growing medicines for treating it. Bexagliflozin, approved by the US FDA in 2023, is the newest member of this family, yet it has received far less attention than older gliflozins such as dapagliflozin and empagliflozin. This review brings together topics that are usually spread across separate papers: the chemistry behind how these drugs are built, how bexagliflozin is made, how the body is predicted to absorb and process it, results from clinical trials, and possible drug interactions. It also looks ahead to newer drugs that act on two sugar transporters at once and to uses beyond diabetes, such as heart, kidney, and liver disease. Students and chemists can see how a small change in structure makes a drug last longer in the body. Clinicians and pharmacists get a quick overview of the evidence and of medicines that may interact. Drug researchers get a starting point for designing the next generation of these medicines.
Perspectives
What drew me to this review was how little attention bexagliflozin has received compared with older gliflozins such as dapagliflozin and empagliflozin, even though its chemistry is just as interesting. I especially enjoyed tracing the story from phlorizin, the compound first found in apple tree bark, to today’s once-daily tablets. Seeing how a single sturdy carbon-carbon bond helps a drug survive long enough in the body to work was a good reminder of how small chemical details can shape patient care. I also want to be candid about the limits of what the review shows. Several of the absorption and drug-likeness properties come from computer predictions rather than lab measurements, and the clinical trials mostly measured blood sugar, weight, and blood pressure, not long-term heart or kidney outcomes. So I see this article as a starting point, not a final verdict on bexagliflozin. My hope is that students and early-career researchers will read it and feel curious about how chemistry connects directly to treatment, and that some will go on to explore the next generation of these drugs.
Samman Samman
Integral University
Read the Original
This page is a summary of: The Chemistry of Gliflozins: Recent Advancements in SGLT-2 Inhibitors, Cardiovascular & Hematological Agents in Medicinal Chemistry, February 2026, Bentham Science Publishers,
DOI: 10.2174/0118715257423396260126091907.
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