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Tubular effects of sodium–glucose cotransporter 2 inhibitors: intended and unintended consequences
- Source :
- Curr Opin Nephrol Hypertens
- Publication Year :
- 2020
- Publisher :
- Ovid Technologies (Wolters Kluwer Health), 2020.
-
Abstract
- PURPOSE OF REVIEW: Sodium–glucose cotransporter 2 (SGLT2) inhibitors are antihyperglycemic drugs that act by inhibiting renal sodium–glucose cotransport. Here we present new insights into ‘off target’, or indirect, effects of SGLT2 inhibitors. RECENT FINDINGS: SGLT2 inhibition causes an acute increase in urinary glucose excretion. In addition to lowering blood glucose, there are several other effects that contribute to the overall beneficial renal and cardiovascular effects. Reabsorption of about 66% of sodium is accomplished in the proximal tubule and dependent on the sodium–hydrogen exchanger isoform 3 (NHE3). SGLT2 colocalizes with NHE3, and high glucose levels reduce NHE3 activity. The proximal tubule is also responsible for the majority of phosphate (P(i)) reabsorption. SGLT2 inhibition is associated with increases in plasma P(i), fibroblast growth factor 23 and parathyroid hormone levels in nondiabetics and type 2 diabetes mellitus. Studies in humans identified a urate-lowering effect by SGLT2 inhibition which is possibly mediated by urate transporter 1 (URAT1) and/or glucose transporter member 9 in the proximal tubule. Of note, magnesium levels were also found to increase under SGLT2 inhibition, an effect that was preserved in nondiabetic patients with hypomagnesemia. SUMMARY: Cardiorenal effects of SGLT2 inhibition might involve, in addition to direct effects on glucose homeostasis, effects on NHE3, phosphate, urate, and magnesium homeostasis.
- Subjects :
- Fibroblast growth factor 23
medicine.medical_specialty
Sodium-Hydrogen Exchanger 3
Chemistry
Reabsorption
Glucose transporter
Parathyroid hormone
medicine.disease
Article
Hypomagnesemia
Kidney Tubules, Proximal
Endocrinology
Nephrology
Internal medicine
Sodium/Glucose Cotransporter 2
Internal Medicine
medicine
Humans
Hypoglycemic Agents
Glucose homeostasis
Magnesium
Sodium-Glucose Transporter 2 Inhibitors
Homeostasis
Subjects
Details
- ISSN :
- 14736543 and 10624821
- Volume :
- 29
- Database :
- OpenAIRE
- Journal :
- Current Opinion in Nephrology & Hypertension
- Accession number :
- edsair.doi.dedup.....2bf577981849fab3081889edb61b46b4