BACKGROUND Pancreas-kidney transplantation (PKT) is the best therapeutic option for diabetic patients with end-stage renal failure. Peripheral insulin resistance and the percentage of remaining β-cells in the PKT have been little studied in medical literature. METHODS We analyzed PKT performed in our hospital from January 1992 to January 2014, with follow-up for 5 years. Metabolic values related to glycemic were studied, namely, proteinuria, peptide C, glucose, insulin, and glycosylated hemoglobin. We analyzed insulin resistance (homeostatic model assessment [HOMA]-IR), the percentage of remaining β-cells (HOMA-β), and the influence of these variables on the glycemic profile and graft survival. RESULTS In the study period, 156 simultaneous PKT were performed in our center. At 2 years posttransplantation, the median value of HOMA-IR kidney-pancreas was 4. We compared transplantation with lower HOMA-IR (<4) and higher HOMA-IR (>4). HOMA-β (36 [26-67] vs 29 [14-42]; P = .04), glucose (86 [80-90] vs 81 [74-89]; P = .018), and body mass index (BMI; 24 [21-27] vs 21 [19-24]; P = .013) were greater in the group HOMA-IR>4 versus HOMA-IR<4 group, respectively, after 3 months. These differences in glycemic profile were maintained until the first year after transplantation. At 2 and 5 years of follow-up, the HOMA-IR>4 group showed higher glucose levels and greater BMI, but not differences in HOMA-β. At 1 and 5 years posttransplantation, pancreatic graft survival in the HOMA-IR>4 group (82.9% vs 92.5%) was lower compared with the HOMA-IR<4 group (67% vs 87.5%; P = .016). CONCLUSIONS PKT exhibit an altered glycemic profile in the posttransplantation follow-up associated with the percentage of remaining β-cells and peripheral insulin resistance. PKT patients with peripheral insulin resistance showed decreased pancreatic graft survival.