OBJECTIVE: Diabetes may unfavorably influence the outcome of coronavirus disease 19 (COVID-19), but the determinants of this effect are still poorly understood. In this monocentric study, we aimed at evaluating the impact of type 2 diabetes, comorbidities, plasma glucose levels, and antidiabetes medications on the survival of COVID-19 patients. RESEARCH DESIGN AND METHODS: This was a case series involving 387 COVID-19 patients admitted to a single center in the region of Lombardy, the epicenter of the severe acute respiratory syndrome coronavirus 2 pandemic in Italy, between 20 February and 9 April 2020. Medical history, pharmacological treatments, laboratory findings, and clinical outcomes of patients without diabetes and patients with type 2 diabetes were compared. Cox proportional hazards analysis was applied to investigate risk factors associated with mortality. RESULTS: Our samples included 90 patients (23.3%) with type 2 diabetes, who displayed double the mortality rate of subjects without diabetes (42.3% vs. 21.7%, P < 0.001). In spite of this, after correction for age and sex, risk of mortality was significantly associated with a history of hypertension (adjusted hazard ratio [aHR] 1.84, 95% CI 1.15-2.95; P = 0.011), coronary artery disease (aHR 1.56, 95% CI 1.04-2.35; P = 0.031), chronic kidney disease (aHR 2.07, 95% CI 1.27-3.38; P = 0.003), stroke (aHR 2.09, 95% CI 1.23-3.55; P = 0.006), and cancer (aHR 1.57, 95% CI 1.08-2.42; P = 0.04) but not with type 2 diabetes (P = 0.170). In patients with diabetes, elevated plasma glucose (aHR 1.22, 95% CI 1.04-1.44, per mmol/L; P = 0.015) and IL-6 levels at admission (aHR 2.47, 95% CI 1.28-4.78, per 1-SD increase; P = 0.007) as well as treatment with insulin (aHR 3.05, 95% CI 1.57-5.95; P = 0.001) and beta-blockers (aHR 3.20, 95% CI 1.50-6.60; P = 0.001) were independently associated with increased mortality, whereas the use of dipeptidyl peptidase 4 inhibitors was significantly and independently associated with a lower risk of mortality (aHR 0.13, 95% CI 0.02-0.92; P = 0.042). CONCLUSIONS: Plasma glucose levels at admission and antidiabetes drugs may influence the survival of COVID-19 patients affected by type 2 diabetes.