GLP-1 Agonists Linked to Better Outcomes in HCC Patients With Diabetes
A target trial emulation study found that patients with diabetes and hepatocellular carcinoma (HCC) who initiated a GLP-1 receptor agonist had a longer time to cancer recurrence and improved overall survival compared with those who started a DPP-4 inhibitor. These findings suggest GLP-1 receptor agonists may offer additional benefits beyond glycemic control in this population, although confirmation in prospective randomized trials is needed. The study was published in the BMJ Hepatology by Yan-Jun X. and colleagues.
Patient-level EHR data were extracted from 36 tertiary-care hospitals located in China between 2014 and 2023, and clinical follow-up continued until October 1, 2025. Statistical analyses and data preparation were conducted carefully up to 2026. Patients who had been diagnosed with HCC, and also had T2D as a comorbidity condition, having successfully gone through a curative resection surgery with R0 resection of the liver were included in this analysis. In order to satisfy the inclusion criteria of a new user design, patients were required to start a new treatment course either with GLP-1RA or DPP-4i during the postoperative period from day 0 to day 90, and time zero corresponded to the start date of the qualifying prescription for both groups.
The primary analysis estimand used an intention-to-treat approach supplemented by per-protocol analysis for assessing adherence to treatment. Recurrence-free survival (RFS) was considered a primary clinical outcome, considering death due to causes unrelated to recurrence as a competing risk, whereas overall survival (OS) was a secondary endpoint.
Key findings:
- The primary multicenter registry database effectively selected a substantial baseline group of 42,855 patients with both HCC and T2D with liver resection surgery.
- After applying strict inclusion criteria, a final study group comprising 1,249 patients was identified, including 723 DPP-4i starters and 526 GLP-1RA starters.
- Postoperative outcome tracking was done for an extensive median follow-up period of 50.8 months.
- According to weighted intention-to-treat models, initiation of GLP-1RA was significantly associated with improved RFS with a cause-specific hazard ratio of 0.80 (95% CI, 0.67 to 0.96; p = 0.016).
- The results from the secondary analysis on survival revealed that GLP-1RA use was significantly associated with enhanced OS with a hazard ratio of 0.58 (95% CI, 0.47 to 0.71; p < 0.001).
Overall, postoperative GLP-1RA commencement was related to late recurrence and better survival rate than DPP-4i commencement; further studies should confirm this. The significant multi-center database data provide a necessary empirical basis for the field of metabolic oncology, demonstrating that structural treatment of metabolic diseases may influence the progression of primary liver cancer.
Reference:
Xiang Y- J, Liu Z- H, Feng J- K, et al. Gut Epub ahead of print: [please include Day Month Year]. doi:10.1136/ gutjnl-2026-338462
