Effects of Uric Acid-Lowering Treatment on Glycemia: A Systematic Review and Meta-Analysis

Abstract

Background: Serum uric acid levels have been shown to be associated with increased risk of diabetes. However, it remains unclear whether uric acid-lowering therapy (ULT) is associated with improved glycemic status. This study aimed to summarize evidence from randomized controlled trials (RCTs) to investigate whether ULT reduces fasting blood glucose (FBG) and glycated hemoglobin A1c (HbA1c) levels. Methods: PubMed, Embase, and the Cochrane Library were searched from inception until April 10, 2019. Moreover, in order to maximize the search for articles on the same topic, the reference lists of included studies, relevant review articles and systematic reviews were reviewed. Parallel RCTs investigating the effect of ULT on FBG or HbA1c levels were considered for inclusion. An English language restriction was applied. Data were screened and extracted independently by two researchers. Meta-analyses were performed using random-effects models to calculate the weighted mean differences (WMDs) and 95% confidence intervals (CIs). Results: Four trials with 314 patients reported the effect of ULT with allopurinol on FBG and 2 trials with 141 patients reported the effect of ULT with allopurinol on HbA1c. Treatment with allopurinol resulted in a significant decrease in FBG (WMD: −0.61 mmol/L, 95% CI: −0.93 to −0.28), but only a trend of reduction in HbA1c (WMD: −0.47%, 95% CI: −1.16 to 0.22). Notably, the subgroup analyses showed that treatment with allopurinol was associated with reduced FBG levels in patients without diabetes (WMD: −0.60 mmol/L, 95% CI: −0.99 to −0.20), but not in patients with diabetes. In addition, the dose of allopurinol treatment ≥200 mg daily resulted in a reduction of FBG levels (WMD: −0.59 mmol/L, 95% CI: −0.95 to −0.23), whereas low-dose allopurinol (<200 mg daily) had no effect on FBG levels. Conclusions: The findings suggest that ULT with allopurinol may be effective at reducing glycemia, but such an improvement does not appear to be observed in patients with diabetes. The findings require confirmation in additional trials with larger sample sizes.

Disordered Glucose Levels Are Associated with Xanthine Oxidase Activity in Overweight Type 2 Diabetic Women

“…Studies show that treatment with allopurinol, a XO inhibitor, lowered A1C in T2D normotensive patients [ 32 ] and caused a decrease in markers of oxidative stress such as MDA in patients with T2D and mild hypertension [ 33 ]. However, a meta-analysis revealed that XO inhibition may have blood glucose-lowering effects only in individuals without T2D [ 34 ]. Consistent with our results, Kuppusamy et al [ 15 ] showed a strong positive association between A1C and serum XO in patients with T2D suggesting that poor glycemic control is associated with increased XO activity.…”

The association between serum uric acid and diabetic complications in patients with type 2 diabetes mellitus by gender: a cross-sectional study

“…A clinical study from 8,678 patients with gout reports that uric acid-lowering therapy improves insulin resistance and reduces the incidence of T2DM ( Niu et al, 2018 ). However, a meta-analysis included six trials with 455 patients suggests that uric acid-lowering therapy with allopurinol may be effective at reducing glycemia, but such an improvement does not observed in patients with diabetes ( Chen et al, 2020 ) , suggesting that the significance of uric acid to T2DM might not be restricted to the incidence. It is therefore suspected that elevated SUA has some impact on the development and progression of complications associated with T2DM.…”

Elevated serum uric acid is a facilitating mechanism for insulin resistance mediated accumulation of visceral adipose tissue

“…Although we observed better performance of SUA in females, further evaluations of underlying hormonal and physiological assessments should be performed to evaluate a potential sexual dimorphism on the impact of SUA on whole‐body metabolism. Also, lowering SUA levels with allopurinol or other antihyperuricemics has had benefits on overall improvement on metabolic conditions, 32 so our study may provide a therapeutic goal to improve cardiometabolic health. Our study had some strengths and limitations.…”