Mazdutide for Weight Management and Gout in Adults With Obesity

Study Background and Rationale Gout is the most common form of inflammatory arthritis, and its prevalence is rising in parallel with the global obesity epidemic. Obesity is a major risk factor for gout, contributing to hyperuricemia through increased uric acid production and decreased renal excretion. While urate-lowering therapy (ULT) is the cornerstone of gout management, achieving target serum uric acid (SUA) levels and reducing flare frequency remains challenging in obese patients. Mazdutide is a novel, long-acting dual Glucagon-like Peptide-1 Receptor (GLP-1R) and Glucagon Receptor (GCGR) agonist. By simultaneously reducing energy intake and increasing energy expenditure, Mazdutide has demonstrated significant potential for weight reduction and metabolic improvement. This study is designed to investigate whether Mazdutide can reduce the frequency of gout flares in obese patients by addressing the underlying metabolic drivers of the disease. Study Design and Objectives This is a single-arm, open-label, pre-post controlled exploratory clinical study. The primary objective is to evaluate the effect of 52 weeks of Mazdutide treatment on the Annualized Flare Rate (AFR) in adults with obesity and gout, by comparing it to the AFR in the 12 months prior to treatment. Each subject serves as their own control. Secondary objectives include: 1. Assessing the change in serum uric acid (SUA) levels and the proportion of subjects achieving the target SUA level (\<6.0 mg/dL). 2. Evaluating the time to the first gout flare during the treatment period. 3. Measuring the change in body weight and the proportion of subjects achieving ≥5% and ≥10% weight loss. 4. Analyzing changes in metabolic and inflammatory markers, including HbA1c, lipids, eGFR, IL-6, TNF-α, and hsCRP. 5. Assessing health-related quality of life using the EQ-5D-5L questionnaire and pain using the Numerical Rating Scale (NRS). 6. Evaluating the safety and tolerability of Mazdutide in this patient population. Study Population and Eligibility Criteria The study will enroll 30 subjects who meet all of the following key criteria: 1. Age and Gender: Male and female subjects aged 18 to 65 years (inclusive). 2. Obesity Definition: Subjects must have a Body Mass Index (BMI) ≥ 30.0 kg/m². 3. Gout Diagnosis: A confirmed diagnosis of gout based on the 2015 ACR/EULAR classification criteria. 4. Disease Activity: Subjects must have a history of at least 2 gout flares in the past 6 months prior to screening. 5. Background Therapy: Subjects must be on a stable dose of Urate-Lowering Therapy (ULT) for at least 8 weeks prior to enrollment, or have discontinued ULT for at least 8 weeks. Intervention and Study Procedures All enrolled subjects will receive Mazdutide via subcutaneous injection once weekly for 52 weeks, followed by an 8-week follow-up period after discontinuation. The total study duration for each participant is 64 weeks. The dosing regimen involves a stepwise escalation to improve tolerability: Weeks 1-4: 2 mg once weekly. Weeks 5-8: 4 mg once weekly (if tolerated). Weeks 9-12: 6 mg once weekly (if tolerated). Weeks 13-52: 9 mg once weekly (if tolerated). The dose may be adjusted or maintained at a lower level (e.g., 6 mg or 4 mg) based on individual tolerability, weight, and uric acid levels. Subjects will attend regular study visits for safety and efficacy assessments. These visits include physical examinations, vital signs measurement, laboratory tests (hematology, biochemistry, lipids, SUA), and recording of any gout flares or adverse events. Gout flares will be defined and adjudicated according to a standardized protocol. Statistical Analysis The primary endpoint, Annualized Flare Rate (AFR), will be analyzed by comparing the rate during the 52-week treatment period to the rate in the 12 months prior to treatment. A negative binomial regression model will be used to estimate the rate ratio and its 95% confidence interval. Secondary endpoints will be analyzed using appropriate statistical methods, such as mixed-effects models for repeated measures (MMRM) for continuous variables like SUA and body weight, and Kaplan-Meier analysis for time-to-event data.