Metformin Use Associated With Reduced Risk of Hyperuricemia

Investigators of a recent study published in Diabetes, Obesity and Metabolism employed observational and Mendelian randomization (MR) analyses to evaluate the effect of metformin use on urate metabolism and incident gout in patients with diabetes.

This study utilized data from the UK Biobank, a collection of genetic and health information from over 500,000 participants, to investigate the association between metformin use and urate metabolism. The primary objectives included assessing the impact of metformin on urate levels, risk of hyperuricemia, and the incidence of gout in patients with type 2 diabetes.

To explore whether metformin has a causal effect on urate and gout, the researchers identified genetic variants that approximate the glycated hemoglobin (HbA1c)-lowering effect of metformin, and they conducted MR analyses using genetic summary-level data from the CKDGen and FinnGen cohorts. The researchers also assessed the potential mediation effect of body mass index (BMI) and systolic blood pressure on the association between metformin and urate levels. Finally, they performed a nonlinear MR analysis to examine the results across various HbA1c levels.

The study’s findings, based on data from 18,776 patients with type 2 diabetes, revealed several key insights. Regarding urate reduction, metformin use was associated with a decrease in urate levels of approximately −4.3 μmol/L (P=.001). Metformin was also found to reduce the risk of hyperuricemia, with an odds ratio of 0.87 (95% CI, 0.79-0.96).

The use of metformin, however, did not show a significant effect on the incidence of gout.

The study used genetic proxies for the HbA1c-lowering effects of metformin targets. A 0.62% reduction in HbA1c, equivalent to the impact of metformin, was associated with a substantial reduction in urate levels of approximately −12.5 μmol/L (P=.004).

BMI was found to significantly mediate the association between metformin and urate reduction, with 33% of the effect being mediated by BMI.

Nonlinear MR results suggested a linear trend in the effect of metformin on urate reduction across various HbA1c levels, emphasizing the consistency of the urate-lowering impact of metformin use.

“The effect of metformin may reduce urate levels but not incident gout in the general population,” the investigators concluded.