TY  - EJOU
AU  - Dalbeni, Andrea 
AU  - Vicardi, Marco 
AU  - Natola, Leonardo A. 
AU  - Auriemma, Alessandra 
AU  - Stefanini, Bernardo 
AU  - Vivaldi, Caterina 
AU  - Federico, Piera 
AU  - Polloni, Andrea 
AU  - Soldà, Caterina 
AU  - Lani, Lorenzo 
AU  - Garajová, Ingrid 
AU  - Tamberi, Stefano 
AU  - Lorenzo, Stefania De 
AU  - Piscaglia, Fabio 
AU  - Maria, Vincenzo Di 
AU  - Masi, Gianluca 
AU  - Lonardi, Sara 
AU  - Brandi, Giovanni 
AU  - Daniele, Bruno 
AU  - Trevisani, Franco 
AU  - Svegliati-Baroni, Gianluca 
AU  - Schiada, Laura 
AU  - Marra, Fabio 
AU  - Campani, Claudia 
AU  - Celsa, Ciro 
AU  - Cabibbo, Giuseppe 
AU  - Bruccoleri, Mariangela 
AU  - Iavarone, Massimo 
AU  - Stella, Leonardo 
AU  - Ponziani, Francesca R. 
AU  - Pressiani, Tiziana 
AU  - Rimassa, Lorenza 
AU  - Tovoli, Francesco 
AU  - Sacerdoti, David 

TI  - The Effect of Metformin on Atezolizumab/Bevacizumab Treatment in Patients with Hepatocellular Carcinoma and Diabetes
T2  - Oncology Research

PY  - 2026
VL  - 34
IS  - 4
SN  - 1555-3906

AB  -  <b>Objectives:</b> The combination of atezolizumab plus bevacizumab (A+B) represents one of the standards first-line treatments for unresectable hepatocellular carcinoma (HCC). Metformin has garnered attention for its potential antitumour and immunomodulatory properties beyond glycaemic control. This study aimed to assess metformin’s impact in patients with type 2 diabetes mellitus (T2DM) receiving A+B therapy. <b>Methods:</b> This retrospective analysis of a prospectively-maintained multicentre database included 523 patients with HCC treated with A+B from the ARTE (Atezolizumab-bevacizumab Real-life Experience for Treatment of Hepatocellular Carcinoma) dataset across 18 Italian centres (May 2020–January 2024). We evaluated objective response rate (ORR), disease control rate (DCR), progression-free survival (PFS), overall survival (OS), and time to progression (TTP) using Cox regression analysis and Inverse Probability of Treatment Weighting (IPTW) to address confounding. <b>Results:</b> Among 523 patients, 341 (65.2%) did not have diabetes and 182 (34.8%) had T2DM. In the overall population, metformin showed no significant benefit for PFS (HR = 1.15, 95% CI [0.88–1.50], <i>p</i> = 0.316) or OS (HR = 1.28, 95% CI [0.94–1.74], <i>p</i> = 0.124). In the subgroup with T2DM (N = 180), metformin showed no significant benefit for PFS (HR = 1.41, 95% CI [0.97–2.05], <i>p</i> = 0.069), OS (HR = 1.23, 95% CI [0.81–1.86], <i>p</i> = 0.333), or TTP (HR = 0.82, 95% CI [0.53–1.26], <i>p</i> = 0.363). IPTW analysis confirmed these negative findings. <b>Conclusion:</b> This study found no evidence of improved outcomes with metformin use in patients with HCC in particular with T2DM receiving A+B therapy. Routine metformin use should not be expected to enhance A+B efficacy based on current evidence.
KW  - Hepatocellular carcinoma; immune checkpoint inhibitors; type 2 diabetes mellitus; metformin; atezolizumab; bevacizumab

DO  - 10.32604/or.2026.073063