Background <p>People with gout and combined-type hyperuricemia, defined as renal urate overload and renal urate under-excretion, have diminished responsiveness to urate-lowering therapy. Emerging observational data suggest that urine alkalization might improve responsiveness to febuxostat. Hence, this prospective study evaluated the urate-lowering efficacy of citrate mixture added to febuxostat in people with gout and combined-type hyperuricemia.</p> Methods <p>Patients with combined-type hyperuricemia and low urine pH (&lt; 6.2) were prospectively enrolled from a gout clinic. All were treated with febuxostat (initially 20&#xa0;mg daily, escalated to 40&#xa0;mg daily if serum urate (SU) ≥360µmol/L). Citrate mixture (3.5&#xa0;g twice daily, open label) was added according to shared decision of both physician and patient (alkalization vs. non-alkalization). Participants were followed for 12 weeks, with primary endpoint being achievement of SU &lt; 360 µmol/L at final assessment.</p> Results <p>We enrolled 234 eligible patients, with 194 completing 12 weeks follow-up (98 non-alkalization and 96 with alkalization). At week 12, more patients in the alkalization group achieved SU &lt; 360µmol/L (57.3% vs. 39.8%, <i>P</i> &lt; 0.05), with significantly increased renal urate excretion, and lower febuxostat doses (mean ± S.D, 31.9 ± 9.9 vs. 34.7 ± 8.9 mg, <i>P</i> &lt; 0.05). Additionally, metabolic measures including the triglyceride concentration and triglyceride-glucose index were lower, and high-density lipoprotein cholesterol concentration as well as insulin sensitivity were higher in the alkalization group. The incidence of adverse events was similar between groups.</p> Conclusions <p>Adjunctive urine alkalization with febuxostat demonstrated a superior urate-lowering response and improved metabolic abnormalities in male with gout and combined-type hyperuricemia.</p> Trial registration <p>ChiCTR, <a href="http://www.chictr.org.cn">http://www.chictr.org.cn</a>, ChiCTR2100043573.</p>