The effect of glucagon-like peptide-1 receptor agonists on serum uric acid concentration: A systematic review and meta-analysis

Br J Clin Pharmacol. 2022 Aug;88(8):3627-3637. doi: 10.1111/bcp.15344. Epub 2022 Apr 17.

Abstract

Aims: Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) are a class of medications mainly used for the treatment of type 2 diabetes. They improve glucose tolerance, increase insulin secretion and induce weight loss. There is controversy about the effect of GLP-1 RAs on serum uric acid (SUA) concentration. Our systematic review aims to objectively answer whether GLP-1 RAs affect SUA levels.

Methods: We performed a systematic search on PubMed, Web of Science, Embase, Scopus and Google Scholar datasets up to 27August 2021 with a language restriction of English only. Randomized controlled trials, observational studies, uncontrolled trials and conference abstracts were included. Studies with insufficient data, irrelevant types of study and follow-up duration of less than a month were excluded from the review. After critical appraisal by the Joanna Briggs Institute checklists, articles underwent data extraction using a prespecified Microsoft Excel sheet.

Results: Of 1004 identified studies, 17 were eligible for inclusion in this systematic review. Pre- to post-administration analysis of GLP-1 RA effects on SUA demonstrated that GLP-1 RAs could significantly reduce SUA concentration (difference in means -0.341, SE 0.063, P value <0.001). However, when compared to placebo, GLP-1RAs did not perform any better in lowering SUA concentration (difference in means -0.455, SE 0.259, P value 0.079). Surprisingly, the active controls, which included insulin, metformin, sodium-glucose co-transporter 2 (SGLT-2) inhibitors and dipeptidyl-peptidase 4 inhibitors, did outperform GLP-1 RAs in reducing SUA concentration (difference in means 0.250, SE 0.038, P value <0.001).

Conclusions: Administration of GLP-1 RAs can result in a significant reduction in SUA concentration. However, this reduction is less than that seen with the use of insulin, metformin and SGLT-2 inhibitors.

Keywords: GLP-1 RAs; diabetes mellitus; glucagon-like peptide-1 receptor agonists; metabolic syndrome; uric acid.

Publication types

  • Meta-Analysis
  • Review
  • Systematic Review

MeSH terms

  • Diabetes Mellitus, Type 2* / drug therapy
  • Glucagon-Like Peptide 1 / agonists
  • Glucagon-Like Peptide-1 Receptor / agonists
  • Glucose
  • Humans
  • Hypoglycemic Agents / pharmacology
  • Hypoglycemic Agents / therapeutic use
  • Insulin
  • Metformin* / therapeutic use
  • Sodium-Glucose Transporter 2 Inhibitors* / pharmacology
  • Sodium-Glucose Transporter 2 Inhibitors* / therapeutic use
  • Uric Acid

Substances

  • Glucagon-Like Peptide-1 Receptor
  • Hypoglycemic Agents
  • Insulin
  • Sodium-Glucose Transporter 2 Inhibitors
  • Uric Acid
  • Glucagon-Like Peptide 1
  • Metformin
  • Glucose