3-Oxodapagliflozin as a potent and highly selective SGLT2 inhibitor for the treatment of type 2 diabetes

Zhang, Shuo; Wang, Yuli; Liu, Wei; Xie, Yizhen; Liu, Yuqiang; Xu, Weifeng; Li-da, Tang; Wang, Jianwu; Zhao, Guilong

doi:10.1007/s40242-014-4043-9

Cited by 2 publications

(1 citation statement)

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“…125 There are also examples of derivatives of current SGLT2 inhibitors that are particularly potent uricosuric agents, such as 3-oxy dapagliflozin. 126 It is appreciated that increased uric acid elimination in the urine with use of an SGLT2 inhibitor could aggravate the risk of renal calculi, but studies to date have not observed this possible long-term risk. 127 7 | CONCLUSIONS Elevated uric acid concentrations are associated with increased adverse cardiovascular and renal events in diabetic and non-diabetic individuals.…”

Section: (Reduction Of End Points In Non-insulin-dependent Diabetes Mmentioning

confidence: 99%

Uric acid and the cardio‐renal effects of SGLT2 inhibitors

Bailey

2019

Diabetes Obesity Metabolism

132

114

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Sodium/glucose co-transporter-2 (SGLT2) inhibitors, which lower blood glucose by increasing renal glucose elimination, have been shown to reduce the risk of adverse cardiovascular (CV) and renal events in type 2 diabetes. This has been ascribed, in part, to haemodynamic changes, body weight reduction and several possible effects on myocardial, endothelial and tubulo-glomerular functions, as well as to reduced glucotoxicity. This review evaluates evidence that an effect of SGLT2 inhibitors to lower uric acid may also contribute to reduced cardiorenal risk.Chronically elevated circulating uric acid concentrations are associated with increased risk of hypertension, CV disease and chronic kidney disease (CKD). The extent to which uric acid contributes to these conditions, either as a cause or an aggravating factor, remains unclear, but interventions that reduce urate production or increase urate excretion in hyperuricaemic patients have consistently improved cardio-renal prognoses. Uric acid concentrations are often elevated in type 2 diabetes, contributing to the "metabolic syndrome" of CV risk. Treating type 2 diabetes with an SGLT2 inhibitor increases uric acid excretion, reduces circulating uric acid and improves parameters of CV and renal function. This raises the possibility that the lowering of uric acid by SGLT2 inhibition may assist in reducing adverse CV events and slowing progression of CKD in type 2 diabetes. SGLT2 inhibition might also be useful in the treatment of gout and gouty arthritis, especially when co-existent with diabetes. K E Y W O R D Scardiac, gout, obesity, renal, sodium/glucose co-transporter-2 (SGLT2) inhibitor, type 2 diabetes, uric acid | CARDIO-RENAL EFFECTS OF SGLTINHIBITORSSeveral recent large prospective randomized studies in type 2 diabetes have observed reduced CV risk and improved renal function during treatment with an SGLT2 inhibitor. 3 In the EMPA-REG OUTCOME trial, treatment with empagliflozin was associated with a reduced composite 3-point MACE of CV death, nonfatal myocardial infarction (MI) and stroke by 14%; CV mortality was reduced by 38%, overall mortality by 32% and hospitalization for heart failure by 35%. 4 Empagliflozin also reduced by 39% the deterioration in nephropathy, measured as a composite of progression to macroalbuminuria, doubling of

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Section: (Reduction Of End Points In Non-insulin-dependent Diabetes Mmentioning

confidence: 99%