Incidence of pembrolizumab-induced diabetes mellitus in nonsmall cell lung cancer: A systematic review and meta-analysis

Background: Lung cancer is a leading cause of cancer-related deaths. Nonsmall cell lung cancer (NSCLC) is the most common type of lung cancer, accounting for approximately 85% of all lung cancer cases. Pembrolizumab is an immune checkpoint inhibitor that enhances the immune response against cancer. The use of pembrolizumab as an immune checkpoint inhibitor has been reported in several new case reports of diabetes mellitus (DM). However, the risk and incidence of DM in patients with NSCLC treated with pembrolizumab remain unclear. This study aimed to determine the risk and incidence of pembrolizumab-induced DM in patients with NSCLC. Methods: Eligible randomized controlled trials reporting pembrolizumab-induced DM as a treatment-related adverse event in NSCLC patients were included. The review was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses 2020 guidelines, and the study protocol was registered in The International Prospective Register of Systematic Reviews (CRD42024583581). Study selection and data extraction were performed on the retrieved articles. Meta-analyses were conducted using the Mantel–Haenszel statistical method, with the results reported as pooled odds ratios with 95% confidence intervals. Heterogeneity was assessed using funnel plots and Egger’s test. Results: The analysis included 5 randomized controlled trials comprising a total of 3,596 patients. Pembrolizumab was associated with a significantly increased risk of developing DM compared with control treatment, with a 4.54-fold higher risk (odds ratio: 4.54 [95% confidence interval: 1.17–17.64]; p = 0.03; I 2 = 0). Additionally, the pooled incidence of pembrolizumab-induced DM was 0.81% (95% confidence interval: 0.48%–1.36%). Conclusions: Pembrolizumab is associated with a significantly increased risk of developing DM in patients with NSCLC. These findings indicate the need for careful metabolic monitoring during treatment. However, given the rarity of this adverse event and the limited number of included studies, these findings should be interpreted with caution. Further large-scale studies are required to confirm the true magnitude of this risk.