Abstract
IntroductionImmune checkpoint inhibitors (ICIs) have redefined cancer therapeutics. However, they may provoke immune-related adverse events (irAEs), with diabetes potentially altering their patterns. We aimed to investigate whether diabetic cancer patients exhibit a distinctive or intensified irAE pattern.MethodsWe performed a real-world, retrospective pharmacovigilance study of ICIs using the FDA Adverse Event Reporting System from 2011 to 2025. Reports listing anti-PD-1 (Nivolumab, Pembrolizumab, Cemiplimab), anti-PD-L1 (Atezolizumab, Avelumab, Durvalumab), and anti-CTLA-4 (Ipilimumab, Tremelimumab) agents as suspected drugs were extracted. Disproportionality signals were identified with 4 algorithms: Bayesian Confidence Propagation Neural Network, Reporting Odds Ratio, Proportional Reporting Ratio, and Multi-item Gamma Poisson Shrinker. Time-to-onset was calculated from therapy start to event date, modelled with Weibull distributions, and compared across subgroups with non-parametric tests.ResultsOf 22,775,812 FAERS reports, 1886 involved ICIs used in cancer patients with comorbid diabetes. 423 (22.4 %) were fatal and 1463 (77.6 %) non-fatal. Men predominated (71.5 %), and 63.0 % of patients were aged 65-85 years. Combination therapy (anti-CTLA-4 plus PD-1 or PD-L1) accounted for the highest death proportion (29.6 %). Disproportionality analysis revealed the strongest preferred-term signals for pneumonitis/interstitial lung disease, hypothyroidism, and colitis among all diabetic cancer patients receiving ICI therapy. At the system-organ-class level, endocrine, hepatobiliary, and blood/lymphatic disorders showed the most consistent risk across agents. Weibull modelling demonstrated an early-failure pattern (shape β < 1) with a median time-to-onset of 126.6 days overall, shortening to 90.9 days with combination therapy. Fatal subgroup occurred sooner than non-fatal subgroup (median 106.7 vs 132.5 days; P = 0.004).ConclusionDiabetic cancer patients experienced the full spectrum of ICI-associated toxicities, with combination treatments linked to greater lethality. Multidisciplinary surveillance during the first 3-4 months of therapy, glycemic control, and long-term follow-up may be essential to optimize benefit and minimize harm in this expanding population.