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

• Published in: Diabetic medicine 2019-09, Vol.36 (9), p.1075-1081
• Main Authors: Akturk, H. K., Kahramangil, D., Sarwal, A., Hoffecker, L., Murad, M. H., Michels, A. W.
• Format: Article
• Language: English
• Subjects: Antibodies; Antibodies, Monoclonal - adverse effects; Antibodies, Monoclonal - therapeutic use; Apoptosis; B7-H1 Antigen - immunology; Cell Cycle Checkpoints - immunology; Cell death; Diabetes; Diabetes mellitus; Diabetes mellitus (insulin dependent); Diabetes Mellitus, Type 1 - complications; Diabetes Mellitus, Type 1 - drug therapy; Diabetes Mellitus, Type 1 - epidemiology; Diabetic ketoacidosis; Diabetic Ketoacidosis - chemically induced; Diabetic Ketoacidosis - epidemiology; Evidence-based medicine; Humans; Immune checkpoint inhibitors; Immunoglobulins; Incidence; Insulin; Ketoacidosis; Melanoma; Meta-analysis; PD-L1 protein; Programmed Cell Death 1 Receptor - immunology; Systematic review; Systematic Review or Meta‐analysis; Treatment Outcome
• ISSN: 0742-3071; 1464-5491
• DOI: 10.1111/dme.14050

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 HbA1c 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. What's new? This systematic review showed that the majority of people developed immune checkpoint inhibitor‐induced Type 1 diabetes within 3 months of initial treatment. People presenting with Type 1 diabetes‐associated antibodies had a more rapid onset and higher incidence of diabetic ketoacidosis at presentation. Healthcare providers caring for people receiving these state‐of‐the‐art therapies need to be aware of this potential life‐threatening adverse event.