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

Tao Yuan, Shixuan Liu, Yingyue Dong, Yong Fu, Yan Tang, Weigang Zhao, Tao Yuan, Shixuan Liu, Yingyue Dong, Yong Fu, Yan Tang, Weigang Zhao

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 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.

Keywords: Dapagliflozin; Fractional excretion of uric acid; Islet β-cell function; SGLT2 inhibitors; Serum uric acid; Type 2 diabetes mellitus.

Conflict of interest statement

Competing interestsThe authors declared no conflict of interest.

© The Author(s) 2020.

Figures

Fig. 1
Fig. 1
Clinical trial flow chart. T2DM, type 2 diabetes mellitus; NGT, normal glucose tolerance; BMI, body mass index; HbA1c, glycated hemoglobin; SUA, serum uric acid; TC, total cholesterol; TG, triglyceride; LDL-c, low-density lipoprotein cholesterol; HDL-c, high-density lipoprotein cholesterol; UUA, urinary uric acid; UNa, urinary sodium; UCl, urinary chloride; FEUA, fractional excretion of uric acid; FENa, fractional excretion of sodium; FECl, fractional excretion of chloride; OGTT, oral glucose tolerance test; AUCGlu, area under the curve of glucose; AUCIns, area under the curve of insulin; HOMA-IR, homeostasis model assessment of insulin resistance; HOMA-β, homeostasis model assessment of β-cell function; QUICKI, quantitative insulin sensitivity check index; ISIstumvoll, insulin sensitivity index proposed by Stumvoll et al.; ISIMatsuda, insulin sensitivity index proposed by Matsuda et al.; 1st, first; 2nd, second
Fig. 2
Fig. 2
Correlation between SUA levels and FEUA levels before and after treatment. The relationship between the two variables was assessed using Pearson’s correlation coefficient. SUA, serum uric acid; FEUA, fractional excretion of uric acid
Fig. 3
Fig. 3
The comparison of fractional excretion of Na (a), Cl (b) and UA (c) in three groups. * represents statistical significance. FENa, fractional excretion of sodium; FECl, fractional excretion of chloride; FEUA, fractional excretion of uric acid
Fig. 4
Fig. 4
The curve of serum glucose (a), insulin (b) and C-peptide (c) levels in 3-h OGTT in three groups. OGTT, oral glucose tolerance test
Fig. 5
Fig. 5
Correlation between changes in blood glucose and Stumvoll 1st (a) and 2nd (b) phrase indexes. The relationship between the changes was assessed using Pearson’s correlation coefficient. 1st, first; 2nd, second

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