Effects of a Behavioral Weight Loss Intervention and Metformin Treatment on Serum Urate: Results from a Randomized Clinical Trial

Background: Lower body mass index (BMI) has been associated with lower serum urate (SU), but only in observational studies. We sought to determine the effects of behavioral weight loss and metformin treatment on SU in a randomized trial. Methods and Findings: The Survivorship Promotion In Reducing IGF-1 Trial (SPIRIT) was a parallel three-arm randomized controlled trial of overweight/obese adult cancer survivors without gout at a single center in Maryland, United States. Participants were randomized to: (1) coach-directed weight loss (behavioral telephonic coaching), (2) metformin (up to 2000 mg daily), or (3) self-directed weight loss (informational brochures; reference group). SU and BMI were assessed at baseline and at 3, 6, and 12 months post-randomization. The 121 participants had a mean +/- standard deviation (SD) age of 60 +/- 9 years, 79% were female, and 45% were Black. At baseline, BMI was 35 +/- 5 kg/m(2), and SU was 5.6 +/- 1.3 mg/dL. Compared to the self-directed group, at 12 months, the coach-directed group reduced BMI by 0.9 kg/m(2) (95% confidence interval (CI): -1.5, -0.4) and metformin reduced BMI by 0.6 kg/m(2) (95% CI: -1.1, -0.1). However, compared to the self-directed group, the coach-directed group unexpectedly increased SU by 0.3 mg/dL (95% CI: 0.05, 0.6), and metformin non-significantly increased SU by 0.2 mg/dL (95% CI: -0.04, 0.5); these effects were attenuated when analyses included change in estimated glomerular filtration rate (eGFR). Conclusions: In this randomized trial of cancer survivors without gout, reductions in BMI either increased or did not change SU, potentially due to effects on eGFR. These results do not support a focus on BMI reduction for SU reduction; however, long-term studies are needed. ClinicalTrials.gov Registration: NCT02431676.

Automated summary

The study investigated the impact of weight loss and metformin treatment on serum urate in overweight/obese adult cancer survivors. While weight loss reduced BMI in the coach-directed and metformin groups, it unexpectedly increased serum urate in the coach-directed group. These findings suggest that BMI reduction may not necessarily lead to a decrease in serum urate levels. Long-term studies are needed to further investigate this relationship.