Tirzepatide and change in uric acid and its association with weight reduction: post hoc analyses of the SURMOUNT-1 randomised placebo-controlled trial.

OBJECTIVES: This study aimed to test whether tirzepatide, a dual GLP-1RA/GIP agonist, approved for weight management, would be associated with lowered serum uric acid (SUA) levels via its weight reduction properties. METHODS: A post hoc analysis of the SURMOUNT-1 trial, a randomised placebo-controlled trial involving 2539 adults with obesity or overweight (body mass index [BMI] ≥ 30 kg/m 2 or ≥27 kg/m 2 and at least 1 weight-related complication), randomised to tirzepatide (5, 10, or 15 mg) or placebo for 72 weeks. Tirzepatide treatment over 72 weeks decreased weight by up to 20.9%. SUA was measured at baseline and multiple time points during the 72-week study across the 3 active trial arms, and changes were compared to the placebo arm. The association between weight changes and SUA changes was evaluated by mediation analysis. RESULTS: Treatment with all dose groups of tirzepatide was associated with significant reductions in SUA, compared to placebo. At week 72, the mean change in SUA was -0.69 mg/dL (SE: 0.04), -0.92 mg/dL (0.04), and -0.95 mg/dL (0.04) with 5, 10, and 15 mg of tirzepatide (all P < .001), respectively, and -0.18 mg/dL (0.04) with placebo. SUA levels reduced significantly over time compared to placebo, regardless of baseline uric acid quartiles (P = .610) and baseline BMI values (P = .362). Mediation analysis suggested that weight reduction explained 72.7% of SUA reduction. CONCLUSIONS: In this post hoc analysis, in participants with obesity or overweight, tirzepatide was associated with meaningfully reduced SUA levels, regardless of participants' baseline BMI or SUA levels, and appeared to be so primarily via weight reduction. These findings warrant further investigation into the possible role that tirzepatide/intentional weight loss may play in the treatment of patients with gout living with obesity.