Semaglutide 2.4 mg for Obese Patients with MASH: A Cost-Effectiveness Analysis from the Italian NHS Perspective

Enrico Torre,1 Sergio Di Matteo,2 Chiara Martinotti,2 Giacomo Matteo Bruno,3 Alessandro Cabrino,2 Emma Lucia Fogliati,2 Andrea Giusti,4 Marco Barbieri,5 Luigi Carlo Bottaro,6 Giorgio Lorenzo Colombo3 1Diabetology and Metabolic Diseases Unit, ASL3 Genoa, Genoa, Italy; 2Center of Research, SAVE Studi - Health Economics and Outcomes Research, Milan, Italy; 3Department of Drug Sciences, University of Pavia, Pavia, Italy; 4Internal Medicine Unit, ASL3 Genoa, Genoa, Italy; 5Otolaryngology Unit, ASL3 Genoa, Genoa, Italy; 6General Direction, ASL3 Genoa, Genoa, ItalyCorrespondence: Giorgio Lorenzo Colombo, Department of Drug Sciences, University of Pavia, Pavia, Italy, Email giorgiolorenzo.colombo@unipv.itBackground and Objectives: Metabolic dysfunction–associated liver disease (MASLD) and its progression to steatohepatitis (MASH) are highly prevalent among obese patients, contributing substantially to healthcare costs. Semaglutide, a GLP-1 receptor agonist, has shown metabolic and hepatic benefits in this population. This study assessed the cost-effectiveness of Wegovy® (semaglutide 2.4 mg) versus no pharmacological treatment in obese patients with MASH ≤F3 without diabetes, from the perspective of the Italian National Health Service (NHS).Materials and Methods: A cost-effectiveness analysis (CEA) was conducted using a Markov model developed in Microsoft Excel®, adopting the Italian NHS perspective over a 10-year horizon. In line with study perspective, the model included healthcare resource use and direct costs associated with the management of obesity with MASH (≤F3) and related complications (major obesity related complications and liver disease evolution). Since semaglutide 2.4 mg is not yet reimbursed in Italy, cost assumptions were applied. The target population was estimated from epidemiological data, and utility values were derived from international literature, reflecting the relationship between weight loss and improved quality of life. Costs and outcomes were discounted at 3% annually. Model robustness was tested through one-way deterministic sensitivity analyses (OWSAs).Results: The base case estimated 782,920 obese adults in Italy with MASH ≤F3 without diabetes. The analysis yielded an incremental cost-effectiveness ratio (ICER) of € 22,691 per QALY gained over 10 years, below the accepted Italian willingness-to-pay thresholds. OWSAs confirmed the robustness of results.Conclusion: Semaglutide 2.4 mg is a cost-effective and sustainable option for treating obese patients with MASH ≤F3 in Italy, a subgroup at high risk of progressing to advanced liver disease. By improving both fibrosis and body weight, semaglutide may play a key role in reducing the long-term clinical and economic burden of MASLD.Keywords: obesity, MASLD/MASH, semaglutide 2.4 mg, weight loss, fibrosis reduction, cost-effectiveness