@article{Dalbeni2026, 
author = {Andrea Dalbeni and Marco Vicardi and Leonardo A. Natola and Alessandra Auriemma and Bernardo Stefanini and Caterina Vivaldi and Piera Federico and Andrea Polloni and Caterina Soldà and Lorenzo Lani and Ingrid Garajová and Stefano Tamberi and Stefania De Lorenzo and Fabio Piscaglia and Vincenzo Di Maria and Gianluca Masi and Sara Lonardi and Giovanni Brandi and Bruno Daniele and Franco Trevisani and Gianluca Svegliati-Baroni and Laura Schiada and Fabio Marra and Claudia Campani and Ciro Celsa and Giuseppe Cabibbo and Mariangela Bruccoleri and Massimo Iavarone and Leonardo Stella and Francesca R. Ponziani and Tiziana Pressiani and Lorenza Rimassa and Francesco Tovoli and David Sacerdoti},
title = {The Effect of Metformin on Atezolizumab/Bevacizumab Treatment in Patients with Hepatocellular Carcinoma and Diabetes},
year = {2026},
journal = {Oncology Research},
volume = {34},
number = {4},
keywords = {Hepatocellular carcinoma, immune checkpoint inhibitors, type 2 diabetes mellitus, metformin, atezolizumab, bevacizumab},
url = {https://www.sciopen.com/article/10.32604/or.2026.073063},
doi = {10.32604/or.2026.073063},
abstract = {ObjectivesThe 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.MethodsThis 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.ResultsAmong 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], p = 0.316) or OS (HR = 1.28, 95% CI [0.94–1.74], p = 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], p = 0.069), OS (HR = 1.23, 95% CI [0.81–1.86], p = 0.333), or TTP (HR = 0.82, 95% CI [0.53–1.26], p = 0.363). IPTW analysis confirmed these negative findings.ConclusionThis 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.}
}