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Background: No previous studies have investigated the use of a premixed insulin analogue in a hospital setting., Objective: To compare the efficacy and safety of treatment with premixed insulin analogue (insulin lispro mix 75/25, LM75/25) with the basal-plus regimen with insulin glargine in hospitalized patients with type 2 diabetes (T2D)., Materials and Methods: A randomized clinical trial in hospitalized patients with T2D and glucose >140 mg/dL on admission was performed. A total of 54 patients were randomized to receive insulin LM75/25 or glargine. In both groups, a correction dose of lispro was administered before meals. Insulin dose was adjusted to obtain a mean blood glucose (BG) between 100 and 140 mg/dL., Results: Improvement in the mean BG after the first day of treatment was similar in both groups (P = 0.470). Glycemic control at the end of follow-up was similar between the group with insulin LM75/25 (131.3 ± 28.4 mg/dL) and insulin glargine (143.8 ± 32.5 mg/dL, P = 0.153). The aim of a BG concentration of <140 mg/dL was obtained in 72% of the patients in the premixed insulin analogue group and 56% of patients in the basal-plus group (P = 0.239). There was no difference in the frequency of hypoglycemia between groups (7 vs. 10, P = 0.529)., Conclusion: Results of this trial indicate that the use of a premixed insulin analogue is as effective and safe as the basal-plus regimen to achieve glycemic control.