Effect of immediate and prolonged GLP‐1 receptor agonist administration on uric acid and kidney clearance: <i>Post‐hoc</i> analyses of four clinical trials

Tonneijck, Lennart; Muskiet, Marcel H.A.; Smits, Mark M.; Bjornstad, Petter; Kramer, Mark H. H.; Diamant, Michaëla; Hoorn, Ewout J.; Joles, Jaap A.; Raalte, Daniël H. van

doi:10.1111/dom.13223

Cited by 28 publications

(33 citation statements)

References 50 publications

(224 reference statements)

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“…[128][129][130] The uric acid-lowering effect of SGLT2 inhibitors may contribute to the cardio-renal benefits associated with this class of glucose-lowering agent (Figure 2), and it is possible that SGLT2 inhibitors may assist in the management of hyperuricaemia in diabetes. [128][129][130] The uric acid-lowering effect of SGLT2 inhibitors may contribute to the cardio-renal benefits associated with this class of glucose-lowering agent (Figure 2), and it is possible that SGLT2 inhibitors may assist in the management of hyperuricaemia in diabetes.…”

Section: Glut9bmentioning

confidence: 99%

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Uric acid and the cardio‐renal effects of SGLT2 inhibitors

Bailey

2019

Diabetes Obesity Metabolism

145

118

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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: Glut9bmentioning

confidence: 99%

“…inhibitors. [128][129][130] The uric acid-lowering effect of SGLT2 inhibitors may contribute to the cardio-renal benefits associated with this class of glucose-lowering agent (Figure 2), and it is possible that SGLT2 inhibitors may assist in the management of hyperuricaemia in diabetes.…”

Section: Glut9bmentioning

confidence: 99%

Uric acid and the cardio‐renal effects of SGLT2 inhibitors

Bailey

2019

Diabetes Obesity Metabolism

145

118

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“…Increased serum uric acid is also recognized as a risk factor of cardiovascular disease as a result of its association with hypertension, oxidative stress, chronic inflammation, endothelial dysfunction and carotid atherosclerosis [35][36][37] . This improvement in uric acid might not only come from differences in diet and lifestyle, but also from the effect of glucagon-like peptide-1 agonist by increasing absolute urinary excretion of uric acid through inhibiting Na + /H + exchanger type 3 in the renal proximal tubules 38 . Overall, good improvement in all metabolic factors related to metabolic syndrome indicates that low-dose liraglutide not only has a relatively high efficacy in weight reduction, but also a benefit in reducing the risk of cardiovascular disease.…”

Section: Discussionmentioning

confidence: 99%

Evaluation of the efficacy of low‐dose liraglutide in weight control among Taiwanese non‐diabetes patients

Chou

Chuang

2020

J of Diabetes Invest

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Aims/Introduction Obesity and metabolic syndrome are well‐known to be associated with multiple chronic diseases. Currently, high‐dose liraglutide has been used for weight control in non‐diabetic patients. Considering incretin‐based therapy is more effective in Asian populations, the effect of low‐dose liraglutide in weight control among these non‐diabetic groups has not been well evaluated. Our study aimed to evaluate the efficacy of low‐dose liraglutide in weight control among Taiwan patients. Materials and Methods From July 2017 to December 2018, 46 non‐diabetic patients with metabolic syndrome were included. They had received low‐dose liraglutide at 0.6 or 1.2 mg per day for weight reduction for 12 weeks. After then, changes in bodyweight, waist and metabolic factors were examined. Overt bodyweight reduction was defined as a decrease of >5% within 12 weeks. Results With 12 weeks of medication use, both groups showed statistical weight reduction. Higher doses of liraglutide had better efficacy, and 44.4% of patients in the liraglutide 1.2 mg group reached overt weight reduction, whereas just 32.1% in the 0.6 mg group had achieved this. Young age was found to be a predictor factor for a positive finding (odds ratio 0.941, P = 0.037). Early responders with decreased bodyweight of >4.2% within the first 4 weeks indicated a better chance to achieve measurable weight reduction. Conclusions Low‐dose liraglutide still has high efficacy in weight reduction in Taiwanese people, especially for those of younger age.

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“…Blood determinations were performed using conventional assay methods by the Department of Clinical Chemistry in the VU University Medical Center as described. 21 Heparinplasma and urine samples were used to assess inulin and PAH by colorimetric assay after preparation with p-dimethylamino-benzaldehyde for inulin and trichloroacetic acid and indole-3-acetic acid for PAH. 21 Urine concentrations of KIM-1 and NGAL were determined by sandwich ELISA according to the manufacturer's specification (R&D Systems, Minneapolis, MN, USA).…”

Section: Biochemical Measurementsmentioning

confidence: 99%

“…21 Heparinplasma and urine samples were used to assess inulin and PAH by colorimetric assay after preparation with p-dimethylamino-benzaldehyde for inulin and trichloroacetic acid and indole-3-acetic acid for PAH. 21 Urine concentrations of KIM-1 and NGAL were determined by sandwich ELISA according to the manufacturer's specification (R&D Systems, Minneapolis, MN, USA). PUA was measured as urate with an enzymatic colorimetric test (Cobas-C501; Roche Diagnostics, Indianapolis, IN, USA) and urine-pH was buffered to >8.0 with NaOH.…”

Section: Biochemical Measurementsmentioning

confidence: 99%

Plasma uric acid and renal haemodynamics in type 2 diabetes patients

et al. 2019

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Aim Increased plasma uric acid (PUA) concentrations are associated with chronic kidney disease in type 2 diabetes (T2D) patients. The mechanisms involved remain unclear. We investigated the relation between PUA and (intra)renal haemodynamics in T2D patients without overt kidney disease. Methods Eighty‐eight white men and women with T2D were included (age 64 (58–68) years; body mass index 30.9 (28.3–33.6) kg/m2; glycated haemoglobin 7.1 (6.8–7.6)%). Plasma UA and fractional excretion of UA were measured, while glomerular filtration rate (GFR) and effective renal plasma flow (ERPF) were assessed by inulin and PAH‐clearance techniques, respectively. Effective renal vascular resistance was calculated (ERVR). Renal afferent and efferent arteriolar resistances and glomerular hydrostatic pressure were estimated. Relationships between PUA and fractional excretion of UA and (intra)renal haemodynamic parameters were evaluated by multivariable linear regression analyses. Results Plasma UA concentrations were at the higher end of the normal range in most participants: 342 ± 68 μmol/L or 5.7 ± 1.1 mg/dL (mean ± SD). In multivariable analyses, PUA concentrations were negatively associated with GFR (r = −0.471; P = 0.001), ERPF (r = −0.436; P = 0.003) and glomerular hydrostatic pressure (r = −0.427; P = 0.003). In contrast, PUA concentrations had a positive correlation with ERVR (r = 0.474; P = 0.001), but not with efferent vascular resistance. Fractional excretion of UA was not related to renal haemodynamics. Conclusion Plasma UA was negatively associated to GFR, ERPF but positively related to ERVR in T2D patients without overt renal impairment. Plasma UA‐related increase in ERVR may be related to increased arterial afferent tone, which may put the kidney at risk for renal damage through ischaemia.

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Effect of immediate and prolonged GLP‐1 receptor agonist administration on uric acid and kidney clearance: Post‐hoc analyses of four clinical trials

Cited by 28 publications

References 50 publications

Uric acid and the cardio‐renal effects of SGLT2 inhibitors

Uric acid and the cardio‐renal effects of SGLT2 inhibitors

Evaluation of the efficacy of low‐dose liraglutide in weight control among Taiwanese non‐diabetes patients

Plasma uric acid and renal haemodynamics in type 2 diabetes patients

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