The impact of comorbid type 2 diabetes on survival outcomes in patients with solid tumors treated with immune checkpoint inhibitors: a meta-analysis focusing on lung cancer.

Background: Tumor patients with type 2 diabetes mellitus (T2DM) have a more immunosuppressive tumor microenvironment and weaker T-cell immune response to tumors within the tumor compared to non-T2DM patients when treated with immune checkpoint inhibitors (ICIs).In addition, high blood glucose levels may promote tumor immune escape. These factors may lead to a poor response to ICIs treatment in tumor patients with T2DM, affecting treatment prognosis. Although some studies have explored the association between tumor patients with T2DM and the prognosis of ICIs treatment, there is still controversy. Therefore, this study systematically evaluated the impact of T2DM on the prognosis of ICIs treatment in tumor patients through a meta-analysis, aiming to provide more accurate guidance for clinical practice and optimize the treatment strategy for tumor patients with T2DM. Methods: We systematically searched PubMed, Embase, Web of Science, CNKI, and Wanfang Database to collect studies published from the database establishment to January 2026 that investigated the association between tumor patients with T2DM and the prognosis of ICIs treatment. The Risk Of Bias In Non-randomized Studies - of Interventions (ROBINS-I) was used to evaluate the risk of bias. The pooled hazard ratio (HR) and 95% confidence interval (CI) were calculated to assess the association between tumor patients with T2DM and the prognosis of ICIs treatment. The primary outcomes included overall survival (OS) and progression-free survival (PFS). Meta-analysis was conducted using RevMan 5.3 software. Results: A total of six studies were included, involving 1,225 participants. The meta-analysis showed that patients with T2DM who received ICIs treatment had poorer OS (HR = 1.49, 95%CI:1.25-1.77, P < 0.00001) and PFS(HR = 1.38, 95%CI:1.04-1.83, P = 0.03).Subgroup analyses indicated that regardless of sample size (<200 vs >200) or type of survival analysis (univariate vs multivariate), patients with tumors and T2DM who received ICI treatment were consistently associated with poorer OS. Regarding PFS, a worse outcome was observed in T2DM patients when the sample size was less than 200 or when univariate analysis was applied. However, no significant statistical difference in PFS was found between non-T2DM and T2DM patients treated with ICIs when the sample size exceeded 200 or when multivariate analysis was performed. Conclusions: Based on the current limited evidence, this meta-analysis suggests that T2DM may be associated with poor OS in lung cancer patients treated with ICIs. However, due to the small number of included studies, limited sample size, inherent bias risks of the retrospective design, heterogeneity of tumor types, and the instability of PFS results. The conclusion of this study belongs to the 'put forward hypothesis' level and is not yet sufficient to support clinical practice recommendations. The current evidence cannot determine whether glycemic control can improve the efficacy of ICIs. Future studies need to verify this finding through large-sample, prospective cohort studies and clarify the independent impact of glycemic control levels on the efficacy of ICIs.