Novel Hypothesis to Explain Why SGLT2 Inhibitors Inhibit Only 30–50% of Filtered Glucose Load in Humans
نویسندگان
چکیده
Inhibitors of sodium-glucose cotransporter 2 (SGLT2) are a novel class of antidiabetes drugs, and members of this class are under various stages of clinical development for the management of type 2 diabetes mellitus (T2DM). It is widely accepted that SGLT2 is responsible for >80% of the reabsorption of the renal filtered glucose load. However, maximal doses of SGLT2 inhibitors fail to inhibit >50% of the filtered glucose load. Because the clinical efficacy of this group of drugs is entirely dependent on the amount of glucosuria produced, it is important to understand why SGLT2 inhibitors inhibit <50% of the filtered glucose load. In this Perspective, we provide a novel hypothesis that explains this apparent puzzle and discuss some of the clinical implications inherent in this hypothesis.
منابع مشابه
Why Do SGLT2 Inhibitors Inhibit Only 30–50% of Renal Glucose Reabsorption in Humans?
Sodium glucose cotransporter 2 (SGLT2) inhibition is a novel and promising treatment for diabetes under late-stage clinical development. It generally is accepted that SGLT2 mediates 90% of renal glucose reabsorption. However, SGLT2 inhibitors in clinical development inhibit only 30-50% of the filtered glucose load. Why are they unable to inhibit 90% of glucose reabsorption in humans? We will tr...
متن کاملUse of systems pharmacology modeling to elucidate the operating characteristics of SGLT1 and SGLT2 in renal glucose reabsorption in humans
In the kidney, glucose in glomerular filtrate is reabsorbed primarily by sodium-glucose cotransporters 1 (SGLT1) and 2 (SGLT2) along the proximal tubules. SGLT2 has been characterized as a high capacity, low affinity pathway responsible for reabsorption of the majority of filtered glucose in the early part of proximal tubules, and SGLT1 reabsorbs the residual glucose in the distal part. Inhibit...
متن کاملSafety of sodium-glucose co-transporter 2 inhibitors during Ramadan fasting: Evidence, perceptions and guidelines
Sodium-glucose co-transporter 2 (SGLT2) inhibitors are a new glucose-lowering therapy for T2DM with documented benefits on blood glucose, hypertension, weight reduction and long term cardiovascular benefit. They have an inherent osmotic diuretic effect and lead to some volume loss and possible dehydration. There is some concern about the safety of using SGLT2 inhibitors in Muslim type 2 diabete...
متن کاملLP-925219 maximizes urinary glucose excretion in mice by inhibiting both renal SGLT1 and SGLT2
Sodium-glucose cotransporter 2 (SGLT2) inhibitors are a new class of oral anti-diabetic agents that improve glycemic control by inhibiting SGLT2-mediated renal glucose reabsorption. Currently available agents increase urinary glucose excretion (UGE) to <50% of maximal values because they do not inhibit SGLT1, which reabsorbs >50% of filtered glucose when SGLT2 is completely inhibited. This led ...
متن کاملAn Influence of the Estimated Glomerular Filtration Rate on Improvement in Metabolic Parameters by Sodium-Glucose Cotransporter 2 Inhibitors
We systematically reviewed the anti-atherosclerotic effects beyond glucose lowering of sodium-glucose cotransporter 2 (SGLT2) inhibitors in patients with diabetes, and found that SGLT-2 inhibitors are proved to be significantly associated with weight loss and reduction of blood pressure, in addition to lowering plasma glucose, by a relatively large number of studies [1]. However, the studies in...
متن کامل