Does Dapagliflozin Lower Uric Acid?
Yes, dapagliflozin consistently lowers serum uric acid levels by increasing urinary uric acid excretion through mechanisms linked to urinary glucose excretion. 1, 2, 3
Mechanism of Uric Acid Reduction
Dapagliflozin reduces serum uric acid through increased renal excretion rather than decreased production:
Fractional uric acid excretion increases significantly when dapagliflozin is administered, with studies showing increases from 0.9% to 2.9% (P=0.035) after just one week of treatment 3
The uric acid-lowering effect correlates strongly with urinary glucose excretion (r=0.35; P=0.02), suggesting the mechanism involves competition at renal tubular transporters 1
Urate transporter 1 (URAT1) appears to be involved in this process, as the uric acid-lowering effect of empagliflozin (another SGLT2 inhibitor) is attenuated when combined with benzbromarone, a URAT1 blocker 1
Magnitude and Timeline of Effect
The uric acid reduction with dapagliflozin is clinically meaningful and occurs rapidly:
Serum uric acid decreases by approximately 0.8-1.2 mg/dL across multiple studies 1, 2, 3
Effects are evident within one week of initiating therapy, with serum uric acid dropping from 347.75 μmol/L to 273.25 μmol/L (P=0.001) 3
After 3 months of treatment, serum uric acid levels decreased from 9.0 to 8.0 mg/dL, while urinary uric acid percentage increased from 16.1% to 23.6% 2
The effect persists across different metabolic states, including fasting, hyperinsulinemic-euglycemic, and hyperglycemic conditions 1
Clinical Context and Comparative Data
When comparing dapagliflozin to other diabetes medications:
SGLT2 inhibitors (dapagliflozin and empagliflozin) significantly outperform traditional oral antihyperglycemic drugs in reducing serum uric acid, with mean levels dropping from 7.5±2.5 to 6.3±0.8 mg/dL versus 7.1±1.8 to 6.8±2.2 mg/dL in the comparator group (p=0.001) 4
The uric acid-lowering effect occurs independently of glycemic control improvement, though both effects are observed simultaneously 2, 3
Early evidence from 2010 already identified decreased serum uric acid as a beneficial effect of dapagliflozin treatment 5
Important Clinical Considerations
The uric acid-lowering effect is consistent but should not be the primary indication for prescribing dapagliflozin, as the drug is indicated for diabetes management, heart failure, and chronic kidney disease based on major cardiovascular and renal outcome trials 6, 7
This effect may contribute to the renoprotective benefits observed in large outcome trials, as hyperuricemia is associated with cardiovascular and renal complications in diabetes 4
The mechanism differs from traditional uric acid-lowering agents like allopurinol (which inhibits production) or probenecid (which blocks reabsorption), as dapagliflozin's effect is mediated through increased glucose-dependent uric acid excretion 1