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

ABSTRACT: 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-h UUA, fractional excretion of UA (FEUA), serum lipid parameters and 3-h 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 ?-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 ?mol/L before treatment to 273.25?±?43.18 ?mol/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 ?-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 ?-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 ?-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.

SUBMITTER: Yuan T

PROVIDER: S-EPMC7590796 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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

Yuan Tao T Liu Shixuan S Dong Yingyue Y Fu Yong Y Tang Yan Y Zhao Weigang W

Diabetology & metabolic syndrome 20201027

<h4>Background</h4>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.<h4>Methods</h4>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-h UUA, f ...[more]

PMID: 33117454

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Project description:BackgroundHyperuricemia has been proposed to be a risk factor for cardiovascular disease and chronic kidney disease. Since diabetes is often complicated by hypertension and hyperuricemia, efficient therapeutic strategy against these two complications is very important in diabetic treatment. It has been reported that the antihypertensive drug, irbesartan, inhibits the renal uric acid reabsorptive transporters, URAT1 and GLUT9; this result suggests that irbesartan decreases serum uric acid level (SUA).Subjects and methodsA retrospective study of 107 patients with hypertension and diabetes was performed to analyze the effects of irbesartan on blood pressure, estimated glomerular filtration rate (eGFR), and SUA. The follow-up period was 6-12 months. Seventy percent of the patients were diagnosed with diabetic nephropathy stage II-IV. We excluded patients treated with drugs that influenced SUA. The multiple logistic regression analysis was introduced to identify the relative factors for SUA decline. The time-dependent SUA changes were examined in a mixed-linear model.ResultsIrbesartan reduced blood pressure significantly after 1, 6, and 12 months' treatment. No subject showed significant change in eGFR from baseline level throughout the period. The multiple logistic regression analysis revealed that SUA baseline significantly influenced SUA decline after 6-12 months. In patients whose SUA baseline was ?5.9 mg/dL, the SUA was significantly decreased from 6.6±0.16 mg/dL to 6.2±0.16 mg/dL (P=0.010), after 12 months' irbesartan treatment. In the SUA baseline <5.9 mg/dL group, the SUA did not show significant change over the monitoring period.ConclusionOur results demonstrate that irbesartan reduces the risk of hyperuricemia. No decline in renal function was observed after the initiation of irbesartan treatment. The present report determines the criteria of SUA baseline for introducing an antihyperuricemic effect using irbesartan. Its antihypertensive effect coupled with SUA decline would be effective for the treatment of hypertension complicated by hyperuricemia.

Project description:Background. Leprosy reactions are acute inflammatory episodes that occur mainly in the multibacillary forms of the disease. The reactions are classified as type 1 (reverse reaction) or type 2 (erythema nodosum leprosum). Leprosy-associated oxidative stress has been widely demonstrated. Several recent studies have shown uric acid (UA) to have antioxidative effects under pathologic conditions. The objective of this study was to assess serum levels of UA in patients with leprosy reactions, with the aim of monitoring their levels before and after treatment, compared with levels in leprosy patients without reactions. Methods. The study included patients aged 18-69 years assisted at a leprosy treatment reference center in the Central Region of Brazil. Patients who were pregnant; were using immunosuppressant drugs or immunobiologicals; or had an autoimmune disease, human immunodeficiency virus infection, acquired immune deficiency syndrome, or tuberculosis were excluded. Upon recruitment, all individuals were clinically assessed for skin lesions and neural or systemic impairment. Some patients had already completed treatment for leprosy, while others were still undergoing treatment or had initiated treatment after being admitted. The treatment of the reactional episode was started only after the initial evaluation. Laboratory assessments were performed upon admission (baseline) and at approximately 30 and 60 days (time points 1 and 2, respectively). Results. A total of 123 leprosy patients were recruited between June 2012 and June 2015; among them, 56, 42, and 25 presented with type 1, type 2, and no reactions, respectively. Serum UA levels were significantly reduced in patients with type 2 leprosy reactions compared with patients in the control group and remained lower in the two subsequent assessments, after initiation of anti-reaction treatments, with similar values to those recorded before the treatment. Discussion. The decreased serum UA levels in patients with type 2 leprosy reactions might be due to the consumption of UA to neutralize the enhanced production of oxygen- and nitrogen-reactive species that occurs during type 2 reactions. The maintenance of the reduced levels in the follow-up assessments may indicate persistence of oxidative stress in the initial post-treatment stages, despite improved clinical conditions. The results of this study suggest that serum UA may play an antioxidative role during type 2 leprosy reactions.

Dataset Information

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

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

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