The effects of canagliflozin on gout in type 2 diabetes: a post-hoc analysis of the CANVAS Program

Li, Jingwei; Badve, Sunil V.; Zhou, Zien; Rodgers, Anthony; Day, Richard O.; Oh, Richard; Lee, Mary; Perkovic, Vlado; Zeeuw, Dick de; Mahaffey, Kenneth W.; Fulcher, Greg; Neal, Bruce

doi:10.1016/s2665-9913(19)30078-5

Cited by 44 publications

(48 citation statements)

References 33 publications

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“…Recent studies suggest a uricosuric effect of SGLT2 inhibitors [ 130 , 150 , 151 ], although SGLT2 does not appear to have the ability to transport urate [ 152 ]. It is believed that a high glucose concentration in the lumen of proximal tubules may suppress the activity of GLUT9b [ 151 , 152 ].…”

Section: Urate Transporters In Choroid Plexus Epithelial Cellsmentioning

confidence: 99%

Glucose, Fructose, and Urate Transporters in the Choroid Plexus Epithelium

Chiba

Murakami

Matsumoto

et al. 2020

IJMS

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The choroid plexus plays a central role in the regulation of the microenvironment of the central nervous system by secreting the majority of the cerebrospinal fluid and controlling its composition, despite that it only represents approximately 1% of the total brain weight. In addition to a variety of transporter and channel proteins for solutes and water, the choroid plexus epithelial cells are equipped with glucose, fructose, and urate transporters that are used as energy sources or antioxidative neuroprotective substrates. This review focuses on the recent advances in the understanding of the transporters of the SLC2A and SLC5A families (GLUT1, SGLT2, GLUT5, GLUT8, and GLUT9), as well as on the urate-transporting URAT1 and BCRP/ABCG2, which are expressed in choroid plexus epithelial cells. The glucose, fructose, and urate transporters repertoire in the choroid plexus epithelium share similar features with the renal proximal tubular epithelium, although some of these transporters exhibit inversely polarized submembrane localization. Since choroid plexus epithelial cells have high energy demands for proper functioning, a decline in the expression and function of these transporters can contribute to the process of age-associated brain impairment and pathophysiology of neurodegenerative diseases.

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Section: Urate Transporters In Choroid Plexus Epithelial Cellsmentioning

confidence: 99%

Glucose, Fructose, and Urate Transporters in the Choroid Plexus Epithelium

Chiba

Murakami

Matsumoto

et al. 2020

IJMS

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“…Post-hoc-Analysen zweier großer doppelt verblindeter RCTs, die das kardiovaskuläre und renale Sicherheitsprofil von Canagliflozin in Patienten mit Diabetes mellitus Typ 2 untersuchten, zeigten eine geringere mittlere Serumharnsäurekonzentration (Reduktion um 6,7 %) sowie eine geringere Inzidenz von Gichtanfällen in mit Canagliflozin behandelten Gruppen [32]. Der SGLT2 (Natrium-Glukose-Cotransporter 2)-Inhibitor Canagliflozin stellt damit eine potenzielle Erweiterung des Armamentariums zur harnsäuresenkenden Therapie und Anfallsprophylaxe dar.…”

Section: Medikamentöse Harnsäuresenkungunclassified

Therapie der Gicht und des akuten Gichtanfalls

Alten¹,

Mischkewitz²

2020

Arthritis und Rheuma

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ZUSAMMENFASSUNGFür die bestmögliche Behandlung der Gicht ist eine umfangreiche Aufklärung des Patienten über die Erkrankung und Therapieoptionen sowie systematisches Screening auf Komorbiditäten und eine Lebensstilmodifikation elementar. Beim Management des akuten Gichtanfalls sollte möglichst frühzeitig mit der medikamentösen Therapie begonnen werden. Hier stehen Colchicin, nichtsteroidale Antirheumatika (NSAR) und Glukokortikoide oral oder intraartikulär oder eine Kombinationstherapie zur Verfügung. Canakinumab ist Mittel der Wahl bei unzureichendem Ansprechen auf die Behandlung. Für bis zu 6 Monate nach einem Anfall ist eine medikamentöse Prophylaxe indiziert. Die harnsäuresenkende Therapie (ULT) sollte zeitnah nach Indikationsstellung begonnen werden. Allopurinol ist Mittel der 1. Wahl. Liegen schwere Nierenfunktionseinschränkungen, Unverträglichkeit oder unzureichendes Therapieansprechen vor, kommen alternativ Urikosurika, Febuxostat oder die Kombination aus einem Urikosurikum mit Febuxostat in Frage. Bei unzureichendem Therapieansprechen ist auch die Kombination von Allopurinol und einem Urikosurikum möglich. Zuletzt kann auch Pegloticase off-label eingesetzt werden. Die Therapieadhärenz der ULT ist unzureichend.

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“…A variety of studies have reported reduced SUA levels after taking SGLT2 inhibitors. A post hoc analysis of prospectively collected data within the CANVAS program reported canagli ozin reduced serum urate concentrations and reduced events related to gout among patients with T2DM 3 . A meta-analysis of 62 randomized controlled trials involving 34 941 patients quanti ed the effect of any of the SGLT2 inhibitors (empagli ozin, canagli ozin, dapagli ozin, tofogli ozin, licogli ozin, or ipragli ozin) on reducing SUA levels in patients with T2DM 27 .…”

Section: Discussionmentioning

confidence: 99%

“…Studies on bene cial effects other than the hypoglycemic effects of SGLT2 inhibitors have attracted increasing attention, including decreasing risk of cardiovascular diseases, heart failure, and kidney diseases, as well as reducing serum uric acid (SUA) levels and events related to gout ares among patients with T2DM 3,45 . In addition, a few studies have found that SGLT2 inhibitors can play a bene cial role in improving insulin resistance and islet β-cell function [6][7][8] , as well as help to reduce weight, increase lipolysis of adipose tissue and reduce fat production after long-term treatment.…”

Section: Introductionmentioning

confidence: 99%

Effects of dapagliflozin on serum and urinary uric acid levels in patients with type 2 diabetes: a prospective pilot trial

Yuan

Liu

Dong

et al. 2020

Preprint

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Background: We aimed to evaluate the effects of short-term therapy with dapagliflozin on serum uric acid (SUA) and urinary uric acid (UUA) levels in patients with type 2 diabetes.Methods: In this prospective pilot trial, 8 patients with type 2 diabetes mellitus were assigned to the treatment group with dapagliflozin 10 mg once daily for one week, and 7 subjects with normal glucose tolerance were recruited into the control group. Data of anthropometric measurements, SUA, 24-hour UUA, fractional excretion of UA (FEUA), serum lipid parameters and 3-hour oral glucose tolerance test (OGTT) were collected in both treatment and control groups; all examinations were repeated after treatment. The area under the curve of glucose (AUCGlu) was calculated to reflect the general glucose levels, while insulin resistance and islet β-cell function were reflected by indexes calculated according to the data obtained from the OGTT.Results: The weight and serum lipid parameters showed no differences before and after treatment with dapagliflozin for one week. We found SUA levels decreased from 347.75 ± 7.75 μmol/L before treatment to 273.25 ± 43.18 μmol/L after treatment, with a statistically significant difference (P=0.001) and was accompanied by a significant increase in FEUA from 0.009 to 0.029 (P=0.035); there was a linear correlation between SUA and FEUA levels. Glucose control, insulin sensitivity and islet β-cell function were improved to a certain extent. We also found a positive correlation between the decrease in glucose levels and the improvement in islet β-cell function.Conclusions: The SUA-lowering effect of dapagliflozin could be driven by increasing UA excretion within one week of treatment, and a certain degree of improvement in glucose levels and islet β-cell function were observed. Trial registration: ClinicalTrials.gov identifier, NCT04014192. Registered 12 July 2019, https://www.clinicaltrials.gov/ct2/show/NCT04014192?term=NCT04014192&draw=2&rank=1. Yes.

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The effects of canagliflozin on gout in type 2 diabetes: a post-hoc analysis of the CANVAS Program

Cited by 44 publications

References 33 publications

Glucose, Fructose, and Urate Transporters in the Choroid Plexus Epithelium

Glucose, Fructose, and Urate Transporters in the Choroid Plexus Epithelium

Therapie der Gicht und des akuten Gichtanfalls

Effects of dapagliflozin on serum and urinary uric acid levels in patients with type 2 diabetes: a prospective pilot trial

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