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

Sattar N, Scilletta S, Stefanski A, Wang H, Daly JW, Linetzky B

Annals of the rheumatic diseases6 Nov 2025

PMID41198460DOI10.1016/j.ard.2025.10.009PepBankPUB-41198460

Publisher page PubMedAsk about this study

Summary

ObjectivesThis 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.MethodsA 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/m² or ≥27 kg/m² 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.ResultsTreatment 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.ConclusionsIn 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.

CC BYText from Europe PMC. Highlighted sentences are the source of results.

Results from this study7

7 results from studies that gave the peptide. 7 results from people.

01HumanRandomized controlled trialEfficacy outcome
In adults with obesity or overweight, tirzepatide 5 mg lowered serum uric acid by 0.69 mg/dL at week 72 versus 0.18 mg/dL with placebo.
In plain wordsIn adults with obesity or overweight, tirzepatide 5 mg lowered blood uric acid more than placebo.
Peptide
Tirzepatide
Outcome
DecreaseSerum uric acid change at week 72, tirzepatide 5 mg
Study
n = 2,539
Comparator
Placebo
Outcome group
Metabolic pathways and metabolomics · Metabolic and weight
Studied dose
5 mg · 72 weeksAs given in this study (human).
Measurements
SUA change
−0.69 mg/dL
tirzepatide 5 mg
SUA change
−0.18 mg/dL
placebo
Source sentences
Summary
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.
1 context sentence(design, population, supporting numbers)
Summary · context
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/m² or ≥27 kg/m² and at least 1 weight-related complication), randomised to tirzepatide (5, 10, or 15 mg) or placebo for 72 weeks.
Show in the study text Report a problemFND-4119846001
02HumanRandomized controlled trialEfficacy outcome
In adults with obesity or overweight, tirzepatide 10 mg lowered serum uric acid by 0.92 mg/dL at week 72 versus 0.18 mg/dL with placebo.
In plain wordsIn adults with obesity or overweight, tirzepatide 10 mg lowered blood uric acid more than placebo.
Peptide
Tirzepatide
Outcome
DecreaseSerum uric acid change at week 72, tirzepatide 10 mg
Study
n = 2,539
Comparator
Placebo
Outcome group
Metabolic pathways and metabolomics · Metabolic and weight
Studied dose
10 mg · 72 weeksAs given in this study (human).
Measurements
SUA change
−0.92 mg/dL
tirzepatide 10 mg
SUA change
−0.18 mg/dL
placebo
Source sentences
Summary
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.
1 context sentence(design, population, supporting numbers)
Summary · context
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/m² or ≥27 kg/m² and at least 1 weight-related complication), randomised to tirzepatide (5, 10, or 15 mg) or placebo for 72 weeks.
Show in the study text Report a problemFND-4119846002
03HumanRandomized controlled trialEfficacy outcome
In adults with obesity or overweight, tirzepatide 15 mg lowered serum uric acid by 0.95 mg/dL at week 72 versus 0.18 mg/dL with placebo.
In plain wordsIn adults with obesity or overweight, tirzepatide 15 mg lowered blood uric acid more than placebo.
Peptide
Tirzepatide
Outcome
DecreaseSerum uric acid change at week 72, tirzepatide 15 mg
Study
n = 2,539
Comparator
Placebo
Outcome group
Metabolic pathways and metabolomics · Metabolic and weight
Studied dose
15 mg · 72 weeksAs given in this study (human).
Measurements
SUA change
−0.95 mg/dL
tirzepatide 15 mg
SUA change
−0.18 mg/dL
placebo
Source sentences
Summary
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.
1 context sentence(design, population, supporting numbers)
Summary · context
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/m² or ≥27 kg/m² and at least 1 weight-related complication), randomised to tirzepatide (5, 10, or 15 mg) or placebo for 72 weeks.
Show in the study text Report a problemFND-4119846003
04HumanRandomized controlled trialEfficacy outcome
Tirzepatide reduced serum uric acid significantly over time versus placebo regardless of baseline uric acid quartile (P = .610).
In plain wordsTirzepatide lowered uric acid more than placebo whatever the starting uric acid level.
Peptide
Tirzepatide
Outcome
DecreaseSerum uric acid reduction regardless of baseline uric acid quartile
Study
n = 2,539
Comparator
Placebo
Outcome group
Metabolic pathways and metabolomics · Metabolic and weight
Studied dose
5, 10 or 15 mg · 72 weeksAs given in this study (human).
Source sentences
Summary
SUA levels reduced significantly over time compared to placebo, regardless of baseline uric acid quartiles (P = .610)
1 context sentence(design, population, supporting numbers)
Summary · context
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/m² or ≥27 kg/m² and at least 1 weight-related complication), randomised to tirzepatide (5, 10, or 15 mg) or placebo for 72 weeks.
Show in the study text Report a problemFND-4119846004
05HumanRandomized controlled trialEfficacy outcome
Tirzepatide reduced serum uric acid significantly over time versus placebo regardless of baseline BMI (P = .362).
In plain wordsTirzepatide lowered uric acid more than placebo whatever the starting BMI.
Peptide
Tirzepatide
Outcome
DecreaseSerum uric acid reduction regardless of baseline BMI
Study
n = 2,539
Comparator
Placebo
Outcome group
Metabolic pathways and metabolomics · Metabolic and weight
Studied dose
5, 10 or 15 mg · 72 weeksAs given in this study (human).
Source sentences
Summary
SUA levels reduced significantly over time compared to placebo, regardless of baseline uric acid quartiles (P = .610) and baseline BMI values (P = .362)
1 context sentence(design, population, supporting numbers)
Summary · context
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/m² or ≥27 kg/m² and at least 1 weight-related complication), randomised to tirzepatide (5, 10, or 15 mg) or placebo for 72 weeks.
Show in the study text Report a problemFND-4119846005
06HumanRandomized controlled trialEfficacy outcome
In adults with obesity or overweight, tirzepatide treatment over 72 weeks decreased weight by up to 20.9%.
In plain wordsIn adults with obesity or overweight, weight fell by up to 20.9% over 72 weeks of tirzepatide treatment.
Peptide
Tirzepatide
Outcome
DecreaseBody weight change over 72 weeks
Study
n = 2,539
Outcome group
Body weight · Metabolic and weight
Studied dose
5, 10 or 15 mg · 72 weeksAs given in this study (human).
Measurements
weight decrease
≤ 20.9%
tirzepatide
Source sentences
Summary
Tirzepatide treatment over 72 weeks decreased weight by up to 20.9%.
1 context sentence(design, population, supporting numbers)
Summary · context
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/m² or ≥27 kg/m² and at least 1 weight-related complication), randomised to tirzepatide (5, 10, or 15 mg) or placebo for 72 weeks.
Show in the study text Report a problemFND-4119846006
07HumanRandomized controlled trialMechanism
Mediation analysis suggested that weight reduction explained 72.7% of the uric acid reduction with tirzepatide.
In plain wordsWeight loss appeared to explain most of the drop in uric acid seen with tirzepatide.
Peptide
Tirzepatide
Outcome
Not applicableShare of uric acid reduction explained by weight reduction
Study
n = 2,539
Outcome group
Metabolic pathways and metabolomics · Metabolic and weight
Studied dose
5, 10 or 15 mg · 72 weeksAs given in this study (human).
Measurements
share mediated by weight reduction
72.7%
SUA reduction
Source sentences
Summary
Mediation analysis suggested that weight reduction explained 72.7% of SUA reduction.
1 context sentence(design, population, supporting numbers)
Summary · context
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/m² or ≥27 kg/m² and at least 1 weight-related complication), randomised to tirzepatide (5, 10, or 15 mg) or placebo for 72 weeks.
Show in the study text Report a problemFND-4119846007

AI wrote and checked these results. AI can make mistakes, so check important results against the source.

Version history

PepBank keeps every version of the data on this study. Status changes from Retraction Watch, Europe PMC and Crossref are listed with their source.

Version 2Current
12 Oct 2026, 12:10 UTC
Study results updated
Version 1
9 Oct 2026, 03:07 UTC
First added · source update from Europe PMC

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