Is tirzepatide (Mounjaro) safe to prescribe in a patient with hyperuricemia (elevated uric acid) and adequate renal function?

Can Tirzepatide Be Given with Elevated Uric Acid?

Yes, tirzepatide can be safely prescribed in patients with hyperuricemia and actually reduces serum uric acid levels significantly through weight loss, making it a potentially beneficial choice in this population.

Evidence for Tirzepatide's Effect on Uric Acid

Tirzepatide, a dual GLP-1/GIP agonist, demonstrates substantial uric acid-lowering effects in patients with obesity or overweight 1. In the SURMOUNT-1 trial post hoc analysis:

• At 72 weeks, tirzepatide reduced serum uric acid by 0.69-0.95 mg/dL (depending on dose: 5,10, or 15 mg) compared to only 0.18 mg/dL with placebo (all P < .001) 1
• Weight reduction explained 72.7% of the uric acid reduction, indicating the mechanism is primarily through metabolic improvement 1
• The uric acid-lowering effect occurred regardless of baseline uric acid levels or BMI, meaning it works across the spectrum of hyperuricemia 1

Clinical Decision Algorithm

Step 1: Assess the Type of Hyperuricemia

If asymptomatic hyperuricemia (no gout history, no tophi, no joint symptoms):

• Tirzepatide is safe and may actually be beneficial 1
• No additional urate-lowering therapy is needed unless uric acid >9 mg/dL with first gout flare, CKD stage ≥3, or urolithiasis 2, 3
• The American College of Rheumatology conditionally recommends against treating asymptomatic hyperuricemia with dedicated urate-lowering drugs 2

If symptomatic hyperuricemia (history of gout, tophi, or frequent flares):

• Tirzepatide is safe and provides additive benefit to standard urate-lowering therapy 1
• Continue or initiate allopurinol targeting serum uric acid <6 mg/dL 2, 3
• Tirzepatide's weight loss effect will complement urate-lowering therapy 1

Step 2: Verify Renal Function

With adequate renal function (eGFR >30 mL/min):

• Tirzepatide has no contraindications related to hyperuricemia 1
• If concurrent allopurinol is needed, start at ≤100 mg/day and titrate every 2-5 weeks 2

With CKD stage 4 or worse (eGFR <30 mL/min):

• Tirzepatide remains safe for hyperuricemia 1
• If allopurinol is needed, start at 50 mg/day 2

Step 3: Monitor and Adjust

• Check serum uric acid at baseline and 12-24 weeks after starting tirzepatide to document the uric acid-lowering effect 1
• If patient develops gout symptoms during tirzepatide therapy, add colchicine 0.5-1 mg/day for prophylaxis and consider allopurinol 2
• Continue monitoring weight and metabolic parameters, as weight reduction drives the uric acid benefit 1

Important Clinical Caveats

Tirzepatide is NOT a replacement for dedicated urate-lowering therapy in established gout:

• Patients with tophi, radiographic damage, or frequent flares (≥2/year) require allopurinol or febuxostat regardless of tirzepatide use 2, 3
• The uric acid reduction from tirzepatide (0.69-0.95 mg/dL) is meaningful but may be insufficient as monotherapy in severe gout 1

Avoid common pitfalls:

• Do not withhold tirzepatide due to elevated uric acid alone—it actually improves the condition 1
• Do not discontinue established urate-lowering therapy when starting tirzepatide; the effects are complementary 2, 1
• Do not assume tirzepatide will prevent all gout flares; patients with severe hyperuricemia (>9 mg/dL) still need dedicated therapy 2, 3

Practical Prescribing Approach

For patients with obesity/overweight and hyperuricemia without gout history:

• Start tirzepatide without hesitation 1
• Monitor uric acid levels but do not add allopurinol unless gout develops 2
• Counsel on lifestyle modifications (limit alcohol, avoid high-fructose beverages, reduce purine-rich foods) 2

For patients with obesity/overweight and established gout:

• Start tirzepatide as indicated for metabolic disease 1
• Ensure patient is on optimized allopurinol (target uric acid <6 mg/dL, or <5 mg/dL if severe gout) 2, 3
• Provide colchicine prophylaxis 0.5-1 mg/day for 6 months when initiating or escalating urate-lowering therapy 2
• Expect additive benefit from tirzepatide's weight loss effect on uric acid control 1