Skip to main content
Erschienen in: Diabetologia 10/2018

22.08.2018 | Review

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

verfasst von: Merlin C. Thomas, David Z. I. Cherney

Erschienen in: Diabetologia | Ausgabe 10/2018

Einloggen, um Zugang zu erhalten

Abstract

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 HbA1c 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.
Anhänge
Nur mit Berechtigung zugänglich
Literatur
1.
Zurück zum Zitat Zaccardi F, Webb DR, Htike ZZ, Youssef D, Khunti K, Davies MJ (2016) Efficacy and safety of sodium-glucose co-transporter-2 inhibitors in type 2 diabetes mellitus: systematic review and network meta-analysis. Diabetes Obes Metab 18:783–794CrossRefPubMed Zaccardi F, Webb DR, Htike ZZ, Youssef D, Khunti K, Davies MJ (2016) Efficacy and safety of sodium-glucose co-transporter-2 inhibitors in type 2 diabetes mellitus: systematic review and network meta-analysis. Diabetes Obes Metab 18:783–794CrossRefPubMed
2.
Zurück zum Zitat Li J, Gong Y, Li C, Lu Y, Liu Y, Shao Y (2017) Long-term efficacy and safety of sodium-glucose cotransporter-2 inhibitors as add-on to metformin treatment in the management of type 2 diabetes mellitus: a meta-analysis. Medicine 96:e7201CrossRefPubMedPubMedCentral Li J, Gong Y, Li C, Lu Y, Liu Y, Shao Y (2017) Long-term efficacy and safety of sodium-glucose cotransporter-2 inhibitors as add-on to metformin treatment in the management of type 2 diabetes mellitus: a meta-analysis. Medicine 96:e7201CrossRefPubMedPubMedCentral
3.
Zurück zum Zitat Roden M, Weng J, Eilbracht J et al (2013) Empagliflozin monotherapy with sitagliptin as an active comparator in patients with type 2 diabetes: a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet Diabetes Endocrinol 1:208–219CrossRefPubMed Roden M, Weng J, Eilbracht J et al (2013) Empagliflozin monotherapy with sitagliptin as an active comparator in patients with type 2 diabetes: a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet Diabetes Endocrinol 1:208–219CrossRefPubMed
4.
Zurück zum Zitat Bujac S, Del Parigi A, Sugg J et al (2014) Patient characteristics are not associated with clinically important differential response to dapagliflozin: a staged analysis of phase 3 data. Diabetes Ther 5:471–482CrossRefPubMedPubMedCentral Bujac S, Del Parigi A, Sugg J et al (2014) Patient characteristics are not associated with clinically important differential response to dapagliflozin: a staged analysis of phase 3 data. Diabetes Ther 5:471–482CrossRefPubMedPubMedCentral
5.
Zurück zum Zitat Abe T, Matsubayashi Y, Yoshida A et al (2018) Predictors of the response of HbA1c and body weight after SGLT2 inhibition. Diabete Metab 44:172–174CrossRefPubMed Abe T, Matsubayashi Y, Yoshida A et al (2018) Predictors of the response of HbA1c and body weight after SGLT2 inhibition. Diabete Metab 44:172–174CrossRefPubMed
6.
Zurück zum Zitat Monnier L, Lapinski H, Colette C (2003) Contributions of fasting and postprandial plasma glucose increments to the overall diurnal hyperglycemia of type 2 diabetic patients: variations with increasing levels of HbA1c. Diabetes Care 26:881–885CrossRefPubMed Monnier L, Lapinski H, Colette C (2003) Contributions of fasting and postprandial plasma glucose increments to the overall diurnal hyperglycemia of type 2 diabetic patients: variations with increasing levels of HbA1c. Diabetes Care 26:881–885CrossRefPubMed
7.
Zurück zum Zitat Matsumura M, Nakatani Y, Tanka S et al (2017) Efficacy of additional canagliflozin administration to type 2 diabetes patients receiving insulin therapy: examination of diurnal glycemic patterns using continuous glucose monitoring (CGM). Diabetes Ther 8:821–827CrossRefPubMedPubMedCentral Matsumura M, Nakatani Y, Tanka S et al (2017) Efficacy of additional canagliflozin administration to type 2 diabetes patients receiving insulin therapy: examination of diurnal glycemic patterns using continuous glucose monitoring (CGM). Diabetes Ther 8:821–827CrossRefPubMedPubMedCentral
8.
Zurück zum Zitat Nishimura R, Osonoi T, Kanada S et al (2015) Effects of luseogliflozin, a sodium-glucose co-transporter 2 inhibitor, on 24-h glucose variability assessed by continuous glucose monitoring in Japanese patients with type 2 diabetes mellitus: a randomized, double-blind, placebo-controlled, crossover study. Diabetes Obes Metab 17:800–804CrossRefPubMedPubMedCentral Nishimura R, Osonoi T, Kanada S et al (2015) Effects of luseogliflozin, a sodium-glucose co-transporter 2 inhibitor, on 24-h glucose variability assessed by continuous glucose monitoring in Japanese patients with type 2 diabetes mellitus: a randomized, double-blind, placebo-controlled, crossover study. Diabetes Obes Metab 17:800–804CrossRefPubMedPubMedCentral
9.
Zurück zum Zitat Ohgaki R, Wei L, Yamada K et al (2016) Interaction of the sodium/glucose cotransporter (SGLT) 2 inhibitor canagliflozin with SGLT1 and SGLT2. J Pharmacol Exp Ther 358:94–102CrossRefPubMed Ohgaki R, Wei L, Yamada K et al (2016) Interaction of the sodium/glucose cotransporter (SGLT) 2 inhibitor canagliflozin with SGLT1 and SGLT2. J Pharmacol Exp Ther 358:94–102CrossRefPubMed
10.
Zurück zum Zitat Hawley SA, Ford RJ, Smith BK et al (2016) The Na+/glucose cotransporter inhibitor canagliflozin activates AMPK by inhibiting mitochondrial function and increasing cellular AMP levels. Diabetes 65:2784–2794CrossRefPubMedPubMedCentral Hawley SA, Ford RJ, Smith BK et al (2016) The Na+/glucose cotransporter inhibitor canagliflozin activates AMPK by inhibiting mitochondrial function and increasing cellular AMP levels. Diabetes 65:2784–2794CrossRefPubMedPubMedCentral
11.
Zurück zum Zitat Cherney DZI, Cooper ME, Tikkanen I et al (2018) Pooled analysis of phase III trials indicate contrasting influences of renal function on blood pressure, body weight, and HbA1c reductions with empagliflozin. Kidney Int 93:231–244CrossRefPubMed Cherney DZI, Cooper ME, Tikkanen I et al (2018) Pooled analysis of phase III trials indicate contrasting influences of renal function on blood pressure, body weight, and HbA1c reductions with empagliflozin. Kidney Int 93:231–244CrossRefPubMed
12.
Zurück zum Zitat Tang H, Cui W, Li D et al (2017) Sodium-glucose co-transporter 2 inhibitors in addition to insulin therapy for management of type 2 diabetes mellitus: a meta-analysis of randomized controlled trials. Diabetes Obes Metab 19:142–147CrossRefPubMed Tang H, Cui W, Li D et al (2017) Sodium-glucose co-transporter 2 inhibitors in addition to insulin therapy for management of type 2 diabetes mellitus: a meta-analysis of randomized controlled trials. Diabetes Obes Metab 19:142–147CrossRefPubMed
13.
Zurück zum Zitat Ferrannini E (2017) Sodium-glucose co-transporters and their inhibition: clinical physiology. Cell Metab 26:27–38CrossRefPubMed Ferrannini E (2017) Sodium-glucose co-transporters and their inhibition: clinical physiology. Cell Metab 26:27–38CrossRefPubMed
14.
Zurück zum Zitat Del Prato S, Nauck M, Duran-Garcia S et al (2015) Long-term glycaemic response and tolerability of dapagliflozin versus a sulphonylurea as add-on therapy to metformin in patients with type 2 diabetes: 4-year data. Diabetes Obes Metab 17:581–590CrossRefPubMed Del Prato S, Nauck M, Duran-Garcia S et al (2015) Long-term glycaemic response and tolerability of dapagliflozin versus a sulphonylurea as add-on therapy to metformin in patients with type 2 diabetes: 4-year data. Diabetes Obes Metab 17:581–590CrossRefPubMed
15.
Zurück zum Zitat Bonner C, Kerr-Conte J, Gmyr V et al (2015) Inhibition of the glucose transporter SGLT2 with dapagliflozin in pancreatic alpha cells triggers glucagon secretion. Nat Med 21:512–517CrossRefPubMed Bonner C, Kerr-Conte J, Gmyr V et al (2015) Inhibition of the glucose transporter SGLT2 with dapagliflozin in pancreatic alpha cells triggers glucagon secretion. Nat Med 21:512–517CrossRefPubMed
16.
Zurück zum Zitat Ferrannini E, Muscelli E, Frascerra S et al (2014) Metabolic response to sodium-glucose cotransporter 2 inhibition in type 2 diabetic patients. J Clin Invest 124:499–508CrossRefPubMedPubMedCentral Ferrannini E, Muscelli E, Frascerra S et al (2014) Metabolic response to sodium-glucose cotransporter 2 inhibition in type 2 diabetic patients. J Clin Invest 124:499–508CrossRefPubMedPubMedCentral
17.
Zurück zum Zitat Sasaki M, Sasako T, Kubota N et al (2017) Dual regulation of gluconeogenesis by insulin and glucose in the proximal tubules of the kidney. Diabetes 66:2339–2350CrossRefPubMed Sasaki M, Sasako T, Kubota N et al (2017) Dual regulation of gluconeogenesis by insulin and glucose in the proximal tubules of the kidney. Diabetes 66:2339–2350CrossRefPubMed
18.
Zurück zum Zitat Sawada Y, Izumida Y, Takeuchi Y et al (2017) Effect of sodium-glucose cotransporter 2 (SGLT2) inhibition on weight loss is partly mediated by liver-brain-adipose neurocircuitry. Biochem Biophys Res Commun 493:40–45CrossRefPubMed Sawada Y, Izumida Y, Takeuchi Y et al (2017) Effect of sodium-glucose cotransporter 2 (SGLT2) inhibition on weight loss is partly mediated by liver-brain-adipose neurocircuitry. Biochem Biophys Res Commun 493:40–45CrossRefPubMed
19.
Zurück zum Zitat Briand F, Mayoux E, Brousseau E et al (2016) Empagliflozin, via switching metabolism toward lipid utilization, moderately increases LDL cholesterol levels through reduced LDL catabolism. Diabetes 65:2032–2038CrossRefPubMed Briand F, Mayoux E, Brousseau E et al (2016) Empagliflozin, via switching metabolism toward lipid utilization, moderately increases LDL cholesterol levels through reduced LDL catabolism. Diabetes 65:2032–2038CrossRefPubMed
20.
Zurück zum Zitat Ferrannini E, Baldi S, Frascerra S et al (2016) Shift to fatty substrate utilization in response to sodium-glucose cotransporter 2 inhibition in subjects without diabetes and patients with type 2 diabetes. Diabetes 65:1190–1195CrossRefPubMed Ferrannini E, Baldi S, Frascerra S et al (2016) Shift to fatty substrate utilization in response to sodium-glucose cotransporter 2 inhibition in subjects without diabetes and patients with type 2 diabetes. Diabetes 65:1190–1195CrossRefPubMed
21.
Zurück zum Zitat Esterline RL, Vaag A, Oscarsson J, Vora J (2018) Mechanisms in endocrinology: SGLT2 inhibitors; clinical benefits by restoration of normal diurnal metabolism? Eur J Endocrinol 178:R113–R125CrossRefPubMed Esterline RL, Vaag A, Oscarsson J, Vora J (2018) Mechanisms in endocrinology: SGLT2 inhibitors; clinical benefits by restoration of normal diurnal metabolism? Eur J Endocrinol 178:R113–R125CrossRefPubMed
22.
Zurück zum Zitat Pareek M, Schauer PR, Kaplan LM, Leiter LA, Rubino F, Bhatt DL (2018) Metabolic surgery: weight loss, diabetes, and beyond. J Am Coll Cardiol 71:670–687CrossRefPubMed Pareek M, Schauer PR, Kaplan LM, Leiter LA, Rubino F, Bhatt DL (2018) Metabolic surgery: weight loss, diabetes, and beyond. J Am Coll Cardiol 71:670–687CrossRefPubMed
23.
Zurück zum Zitat Carlson MG, Campbell PJ (1993) Intensive insulin therapy and weight gain in IDDM. Diabetes 42:1700–1707CrossRefPubMed Carlson MG, Campbell PJ (1993) Intensive insulin therapy and weight gain in IDDM. Diabetes 42:1700–1707CrossRefPubMed
24.
Zurück zum Zitat Shank ML, Del Prato S, DeFronzo RA (1995) Bedtime insulin/daytime glipizide. Effective therapy for sulfonylurea failures in NIDDM. Diabetes 44:165–172CrossRefPubMed Shank ML, Del Prato S, DeFronzo RA (1995) Bedtime insulin/daytime glipizide. Effective therapy for sulfonylurea failures in NIDDM. Diabetes 44:165–172CrossRefPubMed
26.
Zurück zum Zitat Cai X, Yang W, Gao X et al (2018) The association between the dosage of SGLT2 inhibitor and weight reduction in type 2 diabetes patients: a meta-analysis. Obesity 26:70–80CrossRefPubMed Cai X, Yang W, Gao X et al (2018) The association between the dosage of SGLT2 inhibitor and weight reduction in type 2 diabetes patients: a meta-analysis. Obesity 26:70–80CrossRefPubMed
27.
Zurück zum Zitat Kurinami N, Sugiyama S, Nishimura H et al (2018) Clinical factors associated with initial decrease in body-fat percentage induced by add-on sodium-glucose co-transporter 2 inhibitors in patient with type 2 diabetes mellitus. Clin Drug Investig 38:19–27CrossRefPubMed Kurinami N, Sugiyama S, Nishimura H et al (2018) Clinical factors associated with initial decrease in body-fat percentage induced by add-on sodium-glucose co-transporter 2 inhibitors in patient with type 2 diabetes mellitus. Clin Drug Investig 38:19–27CrossRefPubMed
28.
Zurück zum Zitat Bolinder J, Ljunggren O, Kullberg J et al (2012) Effects of dapagliflozin on body weight, total fat mass, and regional adipose tissue distribution in patients with type 2 diabetes mellitus with inadequate glycemic control on metformin. J Clin Endocrinol Metab 97:1020–1031CrossRefPubMed Bolinder J, Ljunggren O, Kullberg J et al (2012) Effects of dapagliflozin on body weight, total fat mass, and regional adipose tissue distribution in patients with type 2 diabetes mellitus with inadequate glycemic control on metformin. J Clin Endocrinol Metab 97:1020–1031CrossRefPubMed
30.
Zurück zum Zitat Devenny JJ, Godonis HE, Harvey SJ, Rooney S, Cullen MJ, Pelleymounter MA (2012) Weight loss induced by chronic dapagliflozin treatment is attenuated by compensatory hyperphagia in diet-induced obese (DIO) rats. Obesity 20:1645–1652CrossRefPubMed Devenny JJ, Godonis HE, Harvey SJ, Rooney S, Cullen MJ, Pelleymounter MA (2012) Weight loss induced by chronic dapagliflozin treatment is attenuated by compensatory hyperphagia in diet-induced obese (DIO) rats. Obesity 20:1645–1652CrossRefPubMed
31.
Zurück zum Zitat Horie I, Abiru N, Hongo R et al (2017) Increased sugar intake as a form of compensatory hyperphagia in patients with type 2 diabetes under dapagliflozin treatment. Diabetes Res Clin Pract 135:178–184CrossRefPubMed Horie I, Abiru N, Hongo R et al (2017) Increased sugar intake as a form of compensatory hyperphagia in patients with type 2 diabetes under dapagliflozin treatment. Diabetes Res Clin Pract 135:178–184CrossRefPubMed
32.
Zurück zum Zitat Veldhorst MA, Westerterp-Plantenga MS, Westerterp KR (2009) Gluconeogenesis and energy expenditure after a high-protein, carbohydrate-free diet. Am J Clin Nutr 90:519–526CrossRefPubMed Veldhorst MA, Westerterp-Plantenga MS, Westerterp KR (2009) Gluconeogenesis and energy expenditure after a high-protein, carbohydrate-free diet. Am J Clin Nutr 90:519–526CrossRefPubMed
33.
Zurück zum Zitat Winwood-Smith HS, Franklin CE, White CR (2017) Low-carbohydrate diet induces metabolic depression: a possible mechanism to conserve glycogen. Am J Physiol Regul Integr Comp Physiol 313:R347–R356CrossRefPubMed Winwood-Smith HS, Franklin CE, White CR (2017) Low-carbohydrate diet induces metabolic depression: a possible mechanism to conserve glycogen. Am J Physiol Regul Integr Comp Physiol 313:R347–R356CrossRefPubMed
34.
Zurück zum Zitat Wang MY, Yu X, Lee Y et al (2017) Dapagliflozin suppresses glucagon signaling in rodent models of diabetes. Proc Natl Acad Sci U S A 114:6611–6616CrossRefPubMedPubMedCentral Wang MY, Yu X, Lee Y et al (2017) Dapagliflozin suppresses glucagon signaling in rodent models of diabetes. Proc Natl Acad Sci U S A 114:6611–6616CrossRefPubMedPubMedCentral
36.
Zurück zum Zitat Heerspink HJ, Perkins BA, Fitchett DH, Husain M, Cherney DZ (2016) Sodium glucose cotransporter 2 inhibitors in the treatment of diabetes: cardiovascular and kidney effects, potential mechanisms and clinical applications. Circulation 134:752–772CrossRefPubMed Heerspink HJ, Perkins BA, Fitchett DH, Husain M, Cherney DZ (2016) Sodium glucose cotransporter 2 inhibitors in the treatment of diabetes: cardiovascular and kidney effects, potential mechanisms and clinical applications. Circulation 134:752–772CrossRefPubMed
37.
Zurück zum Zitat Hallow KM, Gebremichael Y, Helmlinger G, Vallon V (2017) Primary proximal tubule hyperreabsorption and impaired tubular transport counterregulation determine glomerular hyperfiltration in diabetes: a modeling analysis. Am J Physiol Ren Physiol 312:F819–F835CrossRef Hallow KM, Gebremichael Y, Helmlinger G, Vallon V (2017) Primary proximal tubule hyperreabsorption and impaired tubular transport counterregulation determine glomerular hyperfiltration in diabetes: a modeling analysis. Am J Physiol Ren Physiol 312:F819–F835CrossRef
38.
Zurück zum Zitat Vallon V, Thomson SC (2017) Targeting renal glucose reabsorption to treat hyperglycaemia: the pleiotropic effects of SGLT2 inhibition. Diabetologia 60:215–225CrossRefPubMed Vallon V, Thomson SC (2017) Targeting renal glucose reabsorption to treat hyperglycaemia: the pleiotropic effects of SGLT2 inhibition. Diabetologia 60:215–225CrossRefPubMed
39.
Zurück zum Zitat Skrtic M, Yang GK, Perkins BA et al (2014) Characterisation of glomerular haemodynamic responses to SGLT2 inhibition in patients with type 1 diabetes and renal hyperfiltration. Diabetologia 57:2599–2602CrossRefPubMed Skrtic M, Yang GK, Perkins BA et al (2014) Characterisation of glomerular haemodynamic responses to SGLT2 inhibition in patients with type 1 diabetes and renal hyperfiltration. Diabetologia 57:2599–2602CrossRefPubMed
40.
Zurück zum Zitat Cherney DZI, Perkins BA, Soleymanlou N et al (2014) Sodium glucose cotransport-2 inhibition and intrarenal RAS activity in people with type 1 diabetes. Kidney Int 86:1056–1062CrossRef Cherney DZI, Perkins BA, Soleymanlou N et al (2014) Sodium glucose cotransport-2 inhibition and intrarenal RAS activity in people with type 1 diabetes. Kidney Int 86:1056–1062CrossRef
41.
Zurück zum Zitat Cherney DZI, Perkins BA, Soleymanlou N et al (2014) The renal hemodynamic effect of SGLT2 inhibition in patients with type 1 diabetes. Circulation 129:587–597CrossRefPubMed Cherney DZI, Perkins BA, Soleymanlou N et al (2014) The renal hemodynamic effect of SGLT2 inhibition in patients with type 1 diabetes. Circulation 129:587–597CrossRefPubMed
42.
Zurück zum Zitat Wanner C, Inzucchi SE, Lachin JM et al (2016) Empagliflozin and progression of kidney disease in type 2 diabetes. N Engl J Med 375:323–334CrossRefPubMed Wanner C, Inzucchi SE, Lachin JM et al (2016) Empagliflozin and progression of kidney disease in type 2 diabetes. N Engl J Med 375:323–334CrossRefPubMed
43.
Zurück zum Zitat Nadkarni GN, Ferrandino R, Chang A et al (2017) Acute kidney injury in patients on SGLT2 inhibitors: a propensity-matched analysis. Diabetes Care 40:1479–1485CrossRefPubMed Nadkarni GN, Ferrandino R, Chang A et al (2017) Acute kidney injury in patients on SGLT2 inhibitors: a propensity-matched analysis. Diabetes Care 40:1479–1485CrossRefPubMed
44.
Zurück zum Zitat O’Neill J, Fasching A, Pihl L, Patinha D, Franzen S, Palm F (2015) Acute SGLT inhibition normalizes O2 tension in the renal cortex but causes hypoxia in the renal medulla in anaesthetized control and diabetic rats. Am J Physiol Ren Physiol 309:F227–F234CrossRef O’Neill J, Fasching A, Pihl L, Patinha D, Franzen S, Palm F (2015) Acute SGLT inhibition normalizes O2 tension in the renal cortex but causes hypoxia in the renal medulla in anaesthetized control and diabetic rats. Am J Physiol Ren Physiol 309:F227–F234CrossRef
45.
Zurück zum Zitat Ferrannini E, Baldi S, Frascerra S et al (2017) Renal handling of ketones in response to sodium-glucose cotransporter 2 inhibition in patients with type 2 diabetes. Diabetes Care 40:771–776CrossRefPubMed Ferrannini E, Baldi S, Frascerra S et al (2017) Renal handling of ketones in response to sodium-glucose cotransporter 2 inhibition in patients with type 2 diabetes. Diabetes Care 40:771–776CrossRefPubMed
46.
Zurück zum Zitat Thomas MC, Cooper ME, Tsalamandris C, MacIsaac R, Jerums G (2005) Anemia with impaired erythropoietin response in diabetic patients. Arch Intern Med 165:466–469CrossRefPubMed Thomas MC, Cooper ME, Tsalamandris C, MacIsaac R, Jerums G (2005) Anemia with impaired erythropoietin response in diabetic patients. Arch Intern Med 165:466–469CrossRefPubMed
47.
Zurück zum Zitat Cheeseman C (2009) Solute carrier family 2, member 9 and uric acid homeostasis. Curr Opin Nephrol Hypertens 18:428–432CrossRefPubMed Cheeseman C (2009) Solute carrier family 2, member 9 and uric acid homeostasis. Curr Opin Nephrol Hypertens 18:428–432CrossRefPubMed
48.
Zurück zum Zitat Lytvyn Y, Skrtic M, Yang GK, Yip PM, Perkins BA, Cherney DZ (2015) Glycosuria-mediated urinary uric acid excretion in patients with uncomplicated type 1 diabetes mellitus. Am J Physiol Ren Physiol 308:F77–F83CrossRef Lytvyn Y, Skrtic M, Yang GK, Yip PM, Perkins BA, Cherney DZ (2015) Glycosuria-mediated urinary uric acid excretion in patients with uncomplicated type 1 diabetes mellitus. Am J Physiol Ren Physiol 308:F77–F83CrossRef
49.
Zurück zum Zitat Filippatos TD, Tsimihodimos V, Liamis G, Elisaf MS (2018) SGLT2 inhibitors-induced electrolyte abnormalities: an analysis of the associated mechanisms. Diabetes Metab Syndr 12:59–63CrossRefPubMed Filippatos TD, Tsimihodimos V, Liamis G, Elisaf MS (2018) SGLT2 inhibitors-induced electrolyte abnormalities: an analysis of the associated mechanisms. Diabetes Metab Syndr 12:59–63CrossRefPubMed
50.
Zurück zum Zitat Neal B, Perkovic V, Mahaffey KW et al (2017) Canagliflozin and cardiovascular and renal events in type 2 diabetes. N Engl J Med 377:644–657CrossRefPubMed Neal B, Perkovic V, Mahaffey KW et al (2017) Canagliflozin and cardiovascular and renal events in type 2 diabetes. N Engl J Med 377:644–657CrossRefPubMed
51.
Zurück zum Zitat Heerspink HJ, Desai M, Jardine M, Balis D, Meininger G, Perkovic V (2017) Canagliflozin slows progression of renal function decline independently of glycemic effects. J Am Soc Nephrol 28:368–375CrossRefPubMed Heerspink HJ, Desai M, Jardine M, Balis D, Meininger G, Perkovic V (2017) Canagliflozin slows progression of renal function decline independently of glycemic effects. J Am Soc Nephrol 28:368–375CrossRefPubMed
52.
Zurück zum Zitat Rajasekeran H, Reich HN, Hladunewich MA et al (2018) Dapagliflozin in focal segmental glomerulosclerosis: a combined human-rodent pilot study. Am J Physiol Ren Physiol 314:F412–F422CrossRef Rajasekeran H, Reich HN, Hladunewich MA et al (2018) Dapagliflozin in focal segmental glomerulosclerosis: a combined human-rodent pilot study. Am J Physiol Ren Physiol 314:F412–F422CrossRef
53.
Zurück zum Zitat Cherney DZI, Zinman B, Inzucchi SE et al (2017) Effects of empagliflozin on the urinary albumin-to-creatinine ratio in patients with type 2 diabetes and established cardiovascular disease: an exploratory analysis from the EMPA-REG OUTCOME randomised, placebo-controlled trial. Lancet Diabetes Endocrinol 5:610–621CrossRefPubMed Cherney DZI, Zinman B, Inzucchi SE et al (2017) Effects of empagliflozin on the urinary albumin-to-creatinine ratio in patients with type 2 diabetes and established cardiovascular disease: an exploratory analysis from the EMPA-REG OUTCOME randomised, placebo-controlled trial. Lancet Diabetes Endocrinol 5:610–621CrossRefPubMed
54.
Zurück zum Zitat de Boer IH, Bangalore S, Benetos A et al (2017) Diabetes and hypertension: a position statement by the American Diabetes Association. Diabetes Care 40:1273–1284CrossRefPubMed de Boer IH, Bangalore S, Benetos A et al (2017) Diabetes and hypertension: a position statement by the American Diabetes Association. Diabetes Care 40:1273–1284CrossRefPubMed
55.
Zurück zum Zitat Emdin CA, Rahimi K, Neal B, Callender T, Perkovic V, Patel A (2015) Blood pressure lowering in type 2 diabetes: a systematic review and meta-analysis. JAMA 313:603–615CrossRefPubMed Emdin CA, Rahimi K, Neal B, Callender T, Perkovic V, Patel A (2015) Blood pressure lowering in type 2 diabetes: a systematic review and meta-analysis. JAMA 313:603–615CrossRefPubMed
56.
Zurück zum Zitat Mazidi M, Rezaie P, Gao HK, Kengne AP (2017) Effect of sodium-glucose cotransport-2 inhibitors on blood pressure in people with type 2 diabetes mellitus: a systematic review and meta-analysis of 43 randomized control trials with 22 528 patients. J Am Heart Assoc 6:e004007CrossRefPubMedPubMedCentral Mazidi M, Rezaie P, Gao HK, Kengne AP (2017) Effect of sodium-glucose cotransport-2 inhibitors on blood pressure in people with type 2 diabetes mellitus: a systematic review and meta-analysis of 43 randomized control trials with 22 528 patients. J Am Heart Assoc 6:e004007CrossRefPubMedPubMedCentral
57.
Zurück zum Zitat Rajasekeran H, Kim SJ, Cardella CJ et al (2017) Use of canagliflozin in kidney transplant recipients for the treatment of type 2 diabetes: a case series. Diabetes Care 40:e75–e76CrossRefPubMed Rajasekeran H, Kim SJ, Cardella CJ et al (2017) Use of canagliflozin in kidney transplant recipients for the treatment of type 2 diabetes: a case series. Diabetes Care 40:e75–e76CrossRefPubMed
58.
Zurück zum Zitat Tanaka H, Takano K, Iijima H et al (2017) Factors affecting canagliflozin-induced transient urine volume increase in patients with type 2 diabetes mellitus. Adv Ther 34:436–451CrossRefPubMed Tanaka H, Takano K, Iijima H et al (2017) Factors affecting canagliflozin-induced transient urine volume increase in patients with type 2 diabetes mellitus. Adv Ther 34:436–451CrossRefPubMed
59.
Zurück zum Zitat Karg MV, Bosch A, Kannenkeril D et al (2018) SGLT-2-inhibition with dapagliflozin reduces tissue sodium content: a randomised controlled trial. Cardiovasc Diabetol 17:5CrossRefPubMedPubMedCentral Karg MV, Bosch A, Kannenkeril D et al (2018) SGLT-2-inhibition with dapagliflozin reduces tissue sodium content: a randomised controlled trial. Cardiovasc Diabetol 17:5CrossRefPubMedPubMedCentral
Metadaten
Titel
The actions of SGLT2 inhibitors on metabolism, renal function and blood pressure
verfasst von
Merlin C. Thomas
David Z. I. Cherney
Publikationsdatum
22.08.2018
Verlag
Springer Berlin Heidelberg
Erschienen in
Diabetologia / Ausgabe 10/2018
Print ISSN: 0012-186X
Elektronische ISSN: 1432-0428
DOI
https://doi.org/10.1007/s00125-018-4669-0

Weitere Artikel der Ausgabe 10/2018

Diabetologia 10/2018 Zur Ausgabe

Up Front

Up front

Leitlinien kompakt für die Innere Medizin

Mit medbee Pocketcards sicher entscheiden.

Seit 2022 gehört die medbee GmbH zum Springer Medizin Verlag

Update Innere Medizin

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.