Immune checkpoint inhibitors (ICI) that target programmed cell death protein-1 (PD-1) and its ligand (PD-L1) are beneficial cancer immunotherapies but infrequently cause type 1 diabetes (T1D), which can present with life-threatening diabetic ketoacidosis (DKA). We conducted a systematic review and meta-analysis to understand the timing and factors associated with ICI-induced T1D. We searched MEDLINE, EMBASE, SCOPUS and Cochrane databases (August 2000-2018) for studies of any design on ICI and identified 71 cases in 55 publications. Comparisons were made using Fisher’s exact and Student t-tests. Mean age at T1D presentation was 61.7±12.2 years, 55% were male, and melanoma (53.5%) was the most frequent cancer. Mean duration to T1D onset was only 83.5±88.5 days with DKA in 76% of cases. Average HbA1c was 7.84±1.0% at presentation. All cases had insulin deficiency and required permanent insulin treatment. The majority of patients developed T1D within just 3-months of initial ICI exposure (Figure). Half of the cases reported T1D associated antibodies at diabetes presentation, and those with antibodies had a more rapid onset (p=0.005) and higher incidence of DKA (p=0.02) compared to patients without antibodies. This study provides a framework for prospective clinical studies to screen patients receiving these state-of-the-art therapies for risk factors associated with T1D onset to prevent life-threatening DKA.

H.K. Akturk: Advisory Panel; Self; Sanofi. Research Support; Self; Eli Lilly and Company, MannKind Corporation, REMD Biotherapeutics. Speaker's Bureau; Self; MannKind Corporation. D. Kahramangil: None. A. sarwal: None. M. Murad: None. A. Michels: Stock/Shareholder; Self; IM Therapeutics.


National Institutes of Health (DK108868, DK110845, DK032083)

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