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The actions of SGLT2 inhibitors on metabolism, renal function and blood pressure

Inhibition of the sodium–glucose cotransporter (SGLT) 2 in the proximal tubule of the kidney has a broad range of effects on renal function and plasma volume homeostasis, as well as on adiposity and energy metabolism across the entire body. SGLT2 inhibitors are chiefly used in type 2 diabetes for gl... Full description

Journal Title: Diabetologia 2018-08-22, Vol.61 (10), p.2098-2107
Main Author: Thomas, Merlin C
Other Authors: Cherney, David Z. I
Format: Electronic Article Electronic Article
Language: English
Subjects:
Publisher: Berlin/Heidelberg: Springer Berlin Heidelberg
ID: ISSN: 0012-186X
Link: https://www.ncbi.nlm.nih.gov/pubmed/30132034
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title: The actions of SGLT2 inhibitors on metabolism, renal function and blood pressure
format: Article
creator:
  • Thomas, Merlin C
  • Cherney, David Z. I
subjects:
  • Adipose tissue
  • Adiposity
  • Blood Glucose - metabolism
  • Blood pressure
  • Blood Pressure - drug effects
  • Dextrose
  • Diabetes
  • Diabetes mellitus
  • Diabetes mellitus (non-insulin dependent)
  • Diabetes Mellitus, Type 2 - blood
  • Diabetes Mellitus, Type 2 - drug therapy
  • Diabetic Nephropathies - drug therapy
  • Diabetic Nephropathies - metabolism
  • Energy metabolism
  • Epidermal growth factor receptors
  • Glomerular Filtration Rate
  • Glucose
  • Glucosides - therapeutic use
  • Homeostasis
  • Human Physiology
  • Humans
  • Hyperglycemia - drug therapy
  • Hypoglycemic Agents - pharmacology
  • Internal Medicine
  • Kidney - drug effects
  • Kidney Function Tests
  • Kidneys
  • Medicine
  • Medicine & Public Health
  • Metabolic Diseases
  • Metabolism
  • Physiological aspects
  • Renal function
  • Review
  • Sodium
  • Sodium-Glucose Transporter 2 - metabolism
  • Sodium-Glucose Transporter 2 Inhibitors - pharmacology
  • Type 2 diabetes
  • Urine
  • Weight Loss
ispartof: Diabetologia, 2018-08-22, Vol.61 (10), p.2098-2107
description: Inhibition of the sodium–glucose cotransporter (SGLT) 2 in the proximal tubule of the kidney has a broad range of effects on renal function and plasma volume homeostasis, as well as on adiposity and energy metabolism across the entire body. SGLT2 inhibitors are chiefly used in type 2 diabetes for glucose control, achieving reductions in HbA 1c of 7–10 mmol/mol (0.6–0.9%) when compared with placebo. This glucose-lowering activity is proportional to the ambient glucose concentration and glomerular filtration of this glucose, so may be greater in those with poor glycaemic control and/or hyperfiltration at baseline. Equally, the glucose-lowering effects of SGLT2 inhibitors are attenuated in individuals without diabetes and those with a reduced eGFR. However, unlike the glucose-lowering effects of SGLT2 inhibitors, the spill-over of sodium and glucose beyond the proximal nephron following SGLT2 inhibition triggers dynamic and reversible realignment of energy metabolism, renal filtration and plasma volume without relying on losses into the urine. In addition, these processes are observed in the absence of significant glucosuria or ongoing natriuresis. In the long term, the resetting of energy/salt/water physiology following SGLT2 inhibition has an impact, not only on adiposity, renal function and blood pressure control, but also on the health and survival of patients with type 2 diabetes. A better understanding of the precise biology underlying the acute actions of SGLT2 inhibitors in the kidney and how they are communicated to the rest of the body will likely lead to improved therapeutics that augment similar pathways in individuals with, or even without, diabetes to achieve additional benefits.
language: eng
source:
identifier: ISSN: 0012-186X
fulltext: no_fulltext
issn:
  • 0012-186X
  • 1432-0428
url: Link


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descriptionInhibition of the sodium–glucose cotransporter (SGLT) 2 in the proximal tubule of the kidney has a broad range of effects on renal function and plasma volume homeostasis, as well as on adiposity and energy metabolism across the entire body. SGLT2 inhibitors are chiefly used in type 2 diabetes for glucose control, achieving reductions in HbA 1c of 7–10 mmol/mol (0.6–0.9%) when compared with placebo. This glucose-lowering activity is proportional to the ambient glucose concentration and glomerular filtration of this glucose, so may be greater in those with poor glycaemic control and/or hyperfiltration at baseline. Equally, the glucose-lowering effects of SGLT2 inhibitors are attenuated in individuals without diabetes and those with a reduced eGFR. However, unlike the glucose-lowering effects of SGLT2 inhibitors, the spill-over of sodium and glucose beyond the proximal nephron following SGLT2 inhibition triggers dynamic and reversible realignment of energy metabolism, renal filtration and plasma volume without relying on losses into the urine. In addition, these processes are observed in the absence of significant glucosuria or ongoing natriuresis. In the long term, the resetting of energy/salt/water physiology following SGLT2 inhibition has an impact, not only on adiposity, renal function and blood pressure control, but also on the health and survival of patients with type 2 diabetes. A better understanding of the precise biology underlying the acute actions of SGLT2 inhibitors in the kidney and how they are communicated to the rest of the body will likely lead to improved therapeutics that augment similar pathways in individuals with, or even without, diabetes to achieve additional benefits.
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subjectAdipose tissue ; Adiposity ; Blood Glucose - metabolism ; Blood pressure ; Blood Pressure - drug effects ; Dextrose ; Diabetes ; Diabetes mellitus ; Diabetes mellitus (non-insulin dependent) ; Diabetes Mellitus, Type 2 - blood ; Diabetes Mellitus, Type 2 - drug therapy ; Diabetic Nephropathies - drug therapy ; Diabetic Nephropathies - metabolism ; Energy metabolism ; Epidermal growth factor receptors ; Glomerular Filtration Rate ; Glucose ; Glucosides - therapeutic use ; Homeostasis ; Human Physiology ; Humans ; Hyperglycemia - drug therapy ; Hypoglycemic Agents - pharmacology ; Internal Medicine ; Kidney - drug effects ; Kidney Function Tests ; Kidneys ; Medicine ; Medicine & Public Health ; Metabolic Diseases ; Metabolism ; Physiological aspects ; Renal function ; Review ; Sodium ; Sodium-Glucose Transporter 2 - metabolism ; Sodium-Glucose Transporter 2 Inhibitors - pharmacology ; Type 2 diabetes ; Urine ; Weight Loss
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descriptionInhibition of the sodium–glucose cotransporter (SGLT) 2 in the proximal tubule of the kidney has a broad range of effects on renal function and plasma volume homeostasis, as well as on adiposity and energy metabolism across the entire body. SGLT2 inhibitors are chiefly used in type 2 diabetes for glucose control, achieving reductions in HbA 1c of 7–10 mmol/mol (0.6–0.9%) when compared with placebo. This glucose-lowering activity is proportional to the ambient glucose concentration and glomerular filtration of this glucose, so may be greater in those with poor glycaemic control and/or hyperfiltration at baseline. Equally, the glucose-lowering effects of SGLT2 inhibitors are attenuated in individuals without diabetes and those with a reduced eGFR. However, unlike the glucose-lowering effects of SGLT2 inhibitors, the spill-over of sodium and glucose beyond the proximal nephron following SGLT2 inhibition triggers dynamic and reversible realignment of energy metabolism, renal filtration and plasma volume without relying on losses into the urine. In addition, these processes are observed in the absence of significant glucosuria or ongoing natriuresis. In the long term, the resetting of energy/salt/water physiology following SGLT2 inhibition has an impact, not only on adiposity, renal function and blood pressure control, but also on the health and survival of patients with type 2 diabetes. A better understanding of the precise biology underlying the acute actions of SGLT2 inhibitors in the kidney and how they are communicated to the rest of the body will likely lead to improved therapeutics that augment similar pathways in individuals with, or even without, diabetes to achieve additional benefits.
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3Blood pressure
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5Dextrose
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8Diabetes mellitus (non-insulin dependent)
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14Epidermal growth factor receptors
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17Glucosides - therapeutic use
18Homeostasis
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22Hypoglycemic Agents - pharmacology
23Internal Medicine
24Kidney - drug effects
25Kidney Function Tests
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28Medicine & Public Health
29Metabolic Diseases
30Metabolism
31Physiological aspects
32Renal function
33Review
34Sodium
35Sodium-Glucose Transporter 2 - metabolism
36Sodium-Glucose Transporter 2 Inhibitors - pharmacology
37Type 2 diabetes
38Urine
39Weight Loss
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36Sodium-Glucose Transporter 2 Inhibitors - pharmacology
37Type 2 diabetes
38Urine
39Weight Loss
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abstractInhibition of the sodium–glucose cotransporter (SGLT) 2 in the proximal tubule of the kidney has a broad range of effects on renal function and plasma volume homeostasis, as well as on adiposity and energy metabolism across the entire body. SGLT2 inhibitors are chiefly used in type 2 diabetes for glucose control, achieving reductions in HbA 1c of 7–10 mmol/mol (0.6–0.9%) when compared with placebo. This glucose-lowering activity is proportional to the ambient glucose concentration and glomerular filtration of this glucose, so may be greater in those with poor glycaemic control and/or hyperfiltration at baseline. Equally, the glucose-lowering effects of SGLT2 inhibitors are attenuated in individuals without diabetes and those with a reduced eGFR. However, unlike the glucose-lowering effects of SGLT2 inhibitors, the spill-over of sodium and glucose beyond the proximal nephron following SGLT2 inhibition triggers dynamic and reversible realignment of energy metabolism, renal filtration and plasma volume without relying on losses into the urine. In addition, these processes are observed in the absence of significant glucosuria or ongoing natriuresis. In the long term, the resetting of energy/salt/water physiology following SGLT2 inhibition has an impact, not only on adiposity, renal function and blood pressure control, but also on the health and survival of patients with type 2 diabetes. A better understanding of the precise biology underlying the acute actions of SGLT2 inhibitors in the kidney and how they are communicated to the rest of the body will likely lead to improved therapeutics that augment similar pathways in individuals with, or even without, diabetes to achieve additional benefits.
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