Mazdutide Trial Investigates Portal Pressure Reduction in Overweight Compensated Cirrhosis Patients with CSPH

Patients with compensated cirrhosis and clinically significant portal hypertension (CSPH) face accelerated disease progression and decompensation, often exacerbated by obesity and metabolic abnormalities. Current pharmacological options to lower portal pressure are limited beyond lifestyle interventions. Metabolic dysfunction-associated steatotic liver disease (MASLD) is a leading cause of cirrhosis, with up to one-third of cirrhotic individuals also having class II or III obesity. Mazdutide, a dual GLP-1/glucagon receptor agonist, offers weight-loss and glycemic benefits, making it a promising candidate to address this critical unmet need.

This investigator-initiated, single-arm, open-label, exploratory trial will enroll overweight adults (BMI≥28 or ≥26 with comorbidities) with compensated cirrhosis (viral, MASLD, or alcohol-related) and HVPG≥10 mmHg. Participants will receive Mazdutide via SC injection once weekly for 16 weeks, with dose titration from 2 mg to 4 mg to 6 mg (if tolerated). The primary endpoint is the percentage change in HVPG from baseline to week 16. Secondary endpoints include HVPG response (≥10% decrease or <10 mmHg), decompensation events, and treatment discontinuation due to adverse events. FibroScan® (liver/spleen stiffness, CAP), blood samples for metabolic and liver function, body composition, and nutritional assessments will also be conducted.

This is a trial protocol, and no results are available yet. The study aims to determine if 16-week Mazdutide treatment can safely reduce HVPG in overweight patients with compensated cirrhosis and CSPH. The primary objective is to quantify the percentage change in HVPG from baseline. Researchers will also assess HVPG response, defined as a ≥10% decrease or a reduction to <10 mmHg. Safety and tolerability will be rigorously monitored through adverse event reporting and treatment discontinuation rates. Exploratory endpoints include changes in liver and spleen stiffness, liver fat (CAP), various metabolic parameters (glucose, lipids), and body composition, including muscle mass. The trial seeks to provide preliminary evidence for Mazdutide's potential in mitigating portal hypertension and improving metabolic health in this high-risk population.