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An integral vision of the pharmacology of sodium/glucose co-transporter inhibitors: Past, present, and future

Abstract:

The search for new alternatives for the treatment of diabetes mellitus (DM) has taken a center role in the current preclinical and clinical research in the endocrine-metabolic field due to the aggravating epidemiologic outlook marked by this disease. Modern trends in DM management emphasize the adoption of a patient-centered perspective through the prescription of personalized therapeutic schemes. In this scenario, the introduction of new drugs, such as Na+/glucose co-transporters inhibitors (SGLT2i) or “gliflozins”, has revitalized treatment practices for DM. These agents have shown high efficacy for metabolic control with a reasonable toler-ability profile, which has propelled them to a rapid acceptance in current recommendations for DM treatment. The SGLT2i use leads to a glycosuric effect accompanied by the activation of the glycemic counterregulatory mechanisms and other endocrine changes which favor the control of the disease. However, this inhibition also shows several added benefits, especially in the intestine, in combination with SGLT1 inhibition. Moreover, some gliflozins have been studied for other indications beyond DM, such as obesity, polycystic ovary syndrome, and constipation. This review discusses the pharmacologic foundation of SGLT2 and SGLT1 inhibition, and a peek at the future opportunities with these agents.