PHENTERMINE/TOPIRAMATE reduced uric acid stone volume among patients with obesity and diabetes in an 18-month open-label feasibility trial, with the intervention group also achieving greater weight loss and changes in urinary risk factors.
Nineteen participants with obesity, diabetes mellitus, normal renal function, urine pH below 5.8, and stones comprising at least 80% uric acid were randomised in a 2:1 ratio to phentermine 18.75 mg/topiramate 100 mg or pragmatic controls.
The prospective study used dose escalation and assessed change in computed tomography stone volume as its primary outcome. Secondary outcomes included medication adherence, safety, anthropometric measures, laboratory results, and body composition.
Fifteen participants completed the study, with 73% pill adherence and no serious adverse events. In the intention-to-treat analysis, stone volume decreased by 52% in the intervention group compared with an 8.6% increase in controls (P=0.10).
Per-protocol analysis showed a statistically significant reduction in stone volume (P=0.02). At study end, participants receiving phentermine/topiramate also had greater weight loss than controls (−10.2 versus +2.9 kg) and a greater reduction in haemoglobin A1c (−0.2 versus +0.5).
The intervention group had lower 24-hour urinary citrate (309±81 versus 951±782 mg) and lower uric acid supersaturation (0.7±1.1 versus 1.8±1.0), alongside higher 24-hour urine pH (6.2±0.5 versus 5.5±0.4) and calcium phosphate supersaturation (0.9±0.8 versus 0.2±0.1; all P<0.05).
The researchers concluded that phentermine/topiramate was well tolerated and was associated with significant reductions in stone burden in the per-protocol analysis among patients with obesity, diabetes mellitus, and uric acid nephrolithiasis.
The treatment was also associated with greater weight loss, higher urinary pH, and lower haemoglobin A1c and urinary citrate levels. However, the study was an open-label feasibility trial with only 19 participants, and the primary intention-to-treat analysis did not demonstrate a statistically significant difference in stone volume.
The findings provide a framework for further research evaluating phentermine/topiramate as an alternative approach to uric acid stone management in a broader population of patients with obesity and diabetes.
Canales BK et al. Phentermine/topiramate in obese, diabetic uric acid stone formers: an open-label randomized feasibility trial. J Urol. 2026;216(4):500–10.
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