Abstract
Sodium–glucose co-transporter 2 (SGLT2) inhibitors have been approved as a new class of anti-diabetic drugs for type 2 diabetes mellitus (T2DM). The SGLT2 inhibitors reduce glucose reabsorption through renal systems, thus improving glycemic control in all stages of diabetes mellitus, independent of insulin. This class of drugs has the advantages of no clinically relevant hypoglycemia and working in synergy when combined with currently available anti-diabetic drugs. While improving sugar level control in these patients, SGLT2 inhibitors also have the advantages of blood-pressure improvement and bodyweight reduction, with potential cardiac and renal protection. In randomized control trials for patients with diabetes, SGLT2 inhibitors not only improved cardiovascular and renal outcomes, but also hospitalization for heart failure, with this effect extending to those without diabetes mellitus. Recently, dynamic communication between autophagy and the innate immune system with Beclin 1-TLR9-SIRT3 complexes in response to SGLT2 inhibitors that may serve as a potential treatment strategy for heart failure was discovered. In this review, the background molecular pathways leading to the clinical benefits are examined in this new class of anti-diabetic drugs, the SGLT2 inhibitors.
Highlights
Patients with diabetes mellitus suffer from chronic morbidity with certain disabilities [1,2]
OUTCOME) trial showed that in type 2 diabetes mellitus (T2DM), patients randomized to empagliflozin had cardiovascular benefit independently of baseline hemoglobin A1c (HbA1c) levels and of reductions in HbA1c, including a significant 14% reduction of major adverse cardiovascular event (MACE), which is a composite of myocardial infarction, stroke, and cardiovascular death; a significant 38% reduction of cardiovascular death; a 32% reduction in all-cause death; and a 32% reduction of hospitalization for heart failure (HF) [5]
The Sodium–glucose co-transporter 2 (SGLT2) inhibitors block the reabsorption of sugar in the renal tubules independent of insulin action, and the increased urinary glucose excretion is associated with a lowering of fasting plasma glucose, postprandial glucose, and hemoglobin A1c (HbA1c)
Summary
Patients with diabetes mellitus suffer from chronic morbidity with certain disabilities [1,2]. Anti-diabetic drug development has been one of the most important areas of medical research for this chronic disease affecting more than 463 million in the world [3]. Lead to both glucose and sodium reduction in the blood, resulting in an increase in urinary sodium excretion and reducing the reabsorption of both factors in the kidneys [11]. This effect reduces generalized congestion and intravascular volume, and decreases both cardiac afterload and preload, resulting in improved HF hospitalizations. In a diabetic patient, the heart picks up the use of free fatty acids as a switch from glucose; this in turn impairs cardiac function [12]. Ongoing research studies are conducted to shed more light on the relevance of the ketone hypothesis
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