Phentermine/Topiramate in Obese, Diabetic Uric Acid Stone Formers: An Open-Label Randomized Feasibility Trial.

Abstract

To determine whether medical treatment of obesity, diabetes, and low urine pH with combination phentermine/topiramate affects uric acid (UA) kidney stone burden. Individuals with obesity, diabetes mellitus, normal renal function, urine pH<5.8, and stone analysis ≥80% UA were block randomized (2:1 ratio) to phentermine 18.75 mg/topiramate 100 mg versus pragmatic controls for an 18-month, prospective, open-label feasibility study with dose escalation. Primary outcome was change in computed tomography stone volume. Secondary outcomes included medication adherence, patient safety, and change in anthropometrics, laboratory studies, and body composition. Nineteen participants (age 62.1±9.8 years; 68% male; mean BMI=36.3±2.9 kg/m²) were randomized, and fifteen completed the study with 73% pill adherence and no serious adverse events. Stone volume by intention-to-treat analysis fell 52% in intervention group and rose 8.6% in control group (p=0.10), with per-protocol analysis demonstrating statistically significant stone volume reduction (p=0.02). At study end and compared to means of controls, intervention group had greater weight loss (-10.2 vs +2.9 kg), reduction in HgbA1c levels (-0.2 vs +0.5), lower 24-hour urine citrate (309±81 vs 951±782 mg) and UA supersaturation (0.7±1.1 vs 1.8±1.0) along with higher 24-hour urine pH (6.2±0.5 vs 5.5±0.4) and calcium phosphate supersaturation (0.9±0.8 vs 0.2±0.1) (all p<0.05). Among obese individuals with diabetes mellitus and UA nephrolithiasis, phentermine/topiramate was well tolerated and demonstrated significant stone burden reductions by per-protocol analysis. Intervention group also had greater weight loss, higher urinary pH, and lower HgbA1c and urinary citrate levels. This data provides a framework to study the impact of this novel alternative UA therapy on a wider range of obese and diabetic patients.