This initial 3-arm drug-treatment clinical trial will investigate the use of Etanercept and A1AT to improve IAT function at 90 days and 1 and 2 years post-TPIAT compared to standard care. Forty-five patients undergoing TPIAT will be randomized 1:1:1 to receive either: 1) etanercept (50 mg on day 0; 25 mg on days 3, 7, 10, 14, and 21), 2) alpha-1 antitrypsin (90 mg/kg IV days -1, +3, 7, 14, 21, 28) or 3) standard care. Patients will have mechanistic assessments drawn in the early post-operative period including inflammatory cytokines and chemokines and measures of beta cell loss. Metabolic testing will occur at 90, 365, and 730 days post-TPIAT, including mixed meal tolerance testing, IV glucose tolerance testing, and glucose-potentiated arginine-induced insulin secretion (GPAIS). The latter measures the maximally stimulated acute C-peptide response (ACRmax) as the best estimate of islet mass and the primary endpoint (at day 90) for this study. Results will be used to select the most promising agent for future study in a randomized, blinded multi-center clinical trial.