Immune checkpoint inhibitor-induced Type 1 diabetes: a systematic review and meta-analysis

Aim: To conduct a systematic review and meta-analysis to understand the timing and factors associated with anti-programmed cell death protein-1 (PD-1)/anti-programmed cell death protein-1 ligand (PD-L1) inhibitor-induced Type 1 diabetes. Methods: We searched MEDLINE, EMBASE, SCOPUS and Cochrane databases (August 2000–2018) for studies of any design on immune checkpoint inhibitors. A total of 71 cases were reviewed from 56 publications. Comparisons were made using Fisher's exact and Student's t-tests. Results: The mean ± sd age at Type 1 diabetes presentation was 61.7±12.2 years, 55% of cases were in men, and melanoma (53.5%) was the most frequent cancer. The median time to Type 1 diabetes onset was 49 (5–448) days with ketoacidosis in 76% of cases. The average ± sd HbA_1c concentration was 62 ± 0.3 mmol/mol (7.84±1.0%) at presentation. All cases had insulin deficiency and required permanent exogenous insulin treatment. Half of the cases had Type 1 diabetes-associated antibodies at presentation, and those with antibodies had a more rapid onset (P=0.005) and higher incidence of diabetic ketoacidosis (P=0.02) compared to people without antibodies. Conclusions: Many people developed Type 1 diabetes within 3 months of initial PD-1/PD-L1 inhibitor exposure. People presenting with Type 1 diabetes-associated antibodies had a more rapid onset and higher incidence of ketoacidosis than those without antibodies. Healthcare providers caring for people receiving these state-of-the-art therapies need to be aware of this potential severe adverse event.