Effect of canagliflozin on serum uric acid in patients with type 2 diabetes mellitus

Davies, Melanie J.; Trujillo, Angelina; Vijapurkar, Ujjwala; Damaraju, C. V.; Meininger, Gary

doi:10.1111/dom.12439

Cited by 127 publications

(126 citation statements)

References 13 publications

Supporting

Mentioning

103

Contrasting

Unclassified

Order By: Relevance

“…Moreover, SGLT2 inhibitors reduce SUA levels, possibly due to mediating GLUT9 urate transporter via induction of glycosuria [10,89]. Recent clinical data showed that SGLT2 inhibitors, canagliflozin, dapagliflozin and empagliflozin, reduced SUA levels compared with placebo [8,9]. Ongoing trials may provide further insight into the effects of SGLT2 inhibitors on SUA and renal outcomes.…”

Section: Sglt2 Inhibitorsmentioning

confidence: 99%

“…The debate, however, continues regarding whether hyperuricemia plays a causal role in the progression of CKD or is simply a marker of renal dysfunction [7]. Of most recent, the unexpected finding that sodium glucose transporter 2 (SGLT2) inhibitors for type 2 diabetes mellitus (T2DM) modestly decrease serum uric acid (SUA) sheds light on the UA metabolism in the kidney [8][9][10]. In this review, we will describe the up-to-date knowledge on UA and its metabolism in the setting of CKD and demonstrate a line of evidence when and how to target SUA to inhibit the progression of CKD.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Time to target uric acid to retard CKD progression

et al. 2016

View full text Add to dashboard Cite

Uric acid (UA) remains a possible risk factor of chronic kidney disease (CKD) but its potential role should be elucidated given a fact that multidisciplinary treatments assure a sole strategy to inhibit the progression to end-stage renal disease (ESRD). In clinical setting, most observational studies showed that elevation of serum uric acid (SUA) independently predicts the incidence and the development of CKD. The meta-analysis showed that SUA-lowering therapy with allopurinol may retard the progression of CKD but did not reach conclusive results due to small-sized studies. Larger scale, randomized placebo-controlled trials to assess SUA-lowering therapy are needed. Our recent analysis by propensity score methods has shown that the threshold of SUA should be less than 6.5 mg/dL to abrogate ESRD. In animal models an increase in SUA by the administration of oxonic acid, uricase inhibitor, or nephrectomy can induce glomerular hypertension, arteriolosclerosis including afferent arteriolopathy and tubulointerstitial fibrosis. The ever-growing discoveries of urate transporters prompt us to learn UA metabolism in the kidney and intestine. One example is that the intestinal ABCG2 may play a compensatory role at face of decreased renal clearance of UA in nephrectomized rats, the trigger of which is not a uremic toxin but SUA itself. This review will summarize the recent knowledge on the relationship between SUA and the kidney and try to draw a conclusion when and how to treat asymptomatic hyperuricemia accompanied by CKD. Finally we will address a future perspective on UA study including a Mendelian randomization approach.

show abstract

Section: Sglt2 Inhibitorsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Time to target uric acid to retard CKD progression

et al. 2016

View full text Add to dashboard Cite

show abstract

“…Reduction of serum uric acid levels has been seen with SGLTi-2 due to increased urinary excretion. 29,30 No increase in kidney uric acid stones was observed with SGLTi-2. 30 This new class of drugs has already been shown to reduce glycemic levels in animals and humans with type 1 DM (T1DM), in addition to allowing a reduction in insulin dosage.…”

Section: The Kidney As a Treatment Targetmentioning

confidence: 96%

“…29,30 No increase in kidney uric acid stones was observed with SGLTi-2. 30 This new class of drugs has already been shown to reduce glycemic levels in animals and humans with type 1 DM (T1DM), in addition to allowing a reduction in insulin dosage. [31][32][33] These drugs could, thus, be used as an adjuvant therapy in the treatment of DM1, with low risk of hypoglycemia and without weight gain.…”

Section: The Kidney As a Treatment Targetmentioning

confidence: 96%

Use of SGLT-2 inhibitors in the treatment of type 2 diabetes mellitus

Santos¹,

Lima

Sousa‐Rodrigues³

et al. 2017

Rev. Assoc. Med. Bras.

View full text Add to dashboard Cite

Summary Introduction: Diabetes mellitus is one of the most common chronic diseases in the world, with high morbidity and mortality rates, resulting in a greatly negative socioeconomic impact. Although there are several classes of oral antidiabetic agents, most of the patients are outside the therapeutic goal range. Objective: To review the use of SGLT-2 inhibitors in the treatment of type 2 diabetes mellitus, focusing on their favorable and unfavorable effects, as well as on cardiovascular profile. Method: A literature search on Pubmed database was performed using the following keywords: "SGLT-2 inhibitors," "dapagliflozin," "empagliflozin," "canagliflozin." Results: SGLT-2 inhibitors are a class of oral antidiabetic drugs directed to the kidney. Their mechanism of action is to reduce blood glucose by inducing glycosuria. Extra-glycemic benefits have been described, such as weight loss, decline in blood pressure and levels of triglycerides and uric acid, and they can slow the progression of kidney disease. Genitourinary infections are the main side effects. There is a low risk of hypotension and hypoglycemia. Diabetic ketoacidosis is a serious adverse effect, although rare. Empagliflozin has already had its cardiovascular benefit demonstrated and studies with other drugs are currently being performed. Conclusion: SGLT-2 inhibitors are a new treatment option for type 2 diabetes mellitus, acting independently of insulin. They have potential benefits other than the reduction of blood glucose, but also carry a risk for adverse effects.

show abstract

“…Rasburicase found its application in acute urate nephropathy, as in tumor lysis syndrome. In more recent times, canagliflozin, a glycosuric agent inhibiting the glucose transporter SGLT1, was also found to have uricosuric effect [38]. Incidentally, the serendipitous finding that commonly used drugs exert uricosuric effect is not new, such as in the case of losartan [39], fenofibrate [40] and more recently sevelamer [41].…”

Section: Urate-lowering Therapy (Ult)mentioning

confidence: 99%

Urate-Lowering Agents in Asymptomatic Hyperuricemia: Role of Urine Sediment Analysis and Musculoskeletal Ultrasound

Viggiano

Gigliotti²,

Vallone

et al. 2018

Kidney Blood Press Res

View full text Add to dashboard Cite

Current urate-lowering therapy (ULT) includes three direct acting drugs (allopurinol, febuxostat, Rasburicase) and at least four ‘indirect’ drugs with other important targets (canagliflozin, losartan, fenofibrate and sevelamer). Moreover, the alcalinization of urines using bicarbonate can be used to dissolve urate crystals and the clinician may discontinue several drugs are known to increase serum levels of uric acid, such as diuretics, aspirin, cyclosporine, theophylline, mycophenolate and ACE inhibitors. While there is a consensus to start ULT in cases of symptomatic hyperuricemia (gout, urate-nephrolithiasis), the very frequent conditions of asymptomatic hyperuricemia remains a major conundrum. The effect of asymptomatic hyperuricemia on kidney function has had fluctuating positions over decades. The conflicting results might indicate: (i) the presence of counterbalancing positive and negative effects on kidney function of both serum uric acid and urate-lowering agents, (ii) the presence of a subpopulation of patients, as yet unidentified, which could truly benefit from a urate-lowering therapy. Therefore, today the treatment of asymptomatic hyperuricemia is not recommended nor excluded by current guidelines. Here we suggest that a possible guide for the treatment of asymptomatic hyperuricemia might be the presence of urate crystals in the urine sediment and/or signs of asymptomatic articular damage by urates, identified by musculo-skeletal ultrasound. Moreover, a watchful analysis of the trend in creatinine/eGFR, proteinuria or urate levels might also guide the clinician. Initiation of ULT and follow-up in cases of asymptomatic hyperuricemia should consider urine sediment analysis, musculoskeletal ultrasound and trends in creatinine, proteinuria and serum urate levels.

show abstract

Effect of canagliflozin on serum uric acid in patients with type 2 diabetes mellitus

Cited by 127 publications

References 13 publications

Time to target uric acid to retard CKD progression

Time to target uric acid to retard CKD progression

Use of SGLT-2 inhibitors in the treatment of type 2 diabetes mellitus

Urate-Lowering Agents in Asymptomatic Hyperuricemia: Role of Urine Sediment Analysis and Musculoskeletal Ultrasound

Contact Info

Product

Resources

About