Table 4_Islet function impairment outcomes of immune checkpoint inhibitors in cancer patients: a systematic review and meta-analysis.docx

BackgroundImmune checkpoint inhibitors (ICPis) are associated with islet function impairment (IFI), manifesting as hyperglycemia, diabetes mellitus (DM), or diabetic ketoacidosis (DKA). Delayed detection and management may lead to irreversible β-cell damage and life-threatening complications. We conducted a systematic review and meta-analysis to assess the risk of IFI associated with ICPis.
MethodsFollowing PICOS principles, we searched PubMed, Embase, Cochrane, CNKI, Wanfang, CBM, and VIP databases from inception to October 24, 2024. We included randomized controlled trials (RCTs) comparing ICPis versus non-ICPis regimens in cancer patients. Outcomes included hyperglycemia, DM, and DKA. Risk ratios (RRs) with 95% confidence intervals (CIs) were pooled using fixed- or random-effects models. Quality was assessed with the Cochrane Risk of Bias tool, and publication bias was evaluated by Begg’s test. The protocol was registered with PROSPERO (CRD42025639629).
ResultsA total of 31 RCT studies with 15,417 patients were included in this study. Results showed that ICPis treatment significantly increased the risk of associated IFI (RR = 1.30, 95%CI: 1.10-1.53, P = 0.002), the risk of grade 3-5 (RR = 2.20, 95%CI: 1.50-3.23, P < 0.0001) and type 1 diabetes (T1DM) (RR = 3.38, 95%CI: 1.66-6.88, P = 0.0008) compared to those treated with non-ICPis; Subgroup analysis showed that, compared with non-ICPis, the PD-1 inhibitor and Pembrolizumab groups significantly increased the incidence of developing IFI (RR = 1.57, 95%CI: 1.22-2.01, P = 0.0005; RR = 2.38, 95%CI: 1.43-3.97, P = 0.0009); Patients with NSCLC receiving ICPis had a significantly higher risk of developing IFI compared with non-ICPis (RR = 1.32, 95%CI: 1.01-1.72, P = 0.04). Compared to their respective non-ICPis controls, the point estimate for IFI risk was lower with ICPis plus chemotherapy (RR = 1.23) than with ICPis monotherapy (RR = 1.43); a similar pattern was observed for grade 3–5 IFI (RR = 1.53 vs. 3.39). No publication bias was detected.
ConclusionsICPis significantly increase the risk of IFI, particularly T1DM and severe (grade 3-5) events. PD-1 inhibitors and patients with NSCLC represent high-risk subgroups. We strongly recommend multidisciplinary monitoring and proactive blood glucose management.
Systematic review registrationhttps://www.crd.york.ac.uk/PROSPERO/myprospero, identifier CRD42025639629