• Katherine Esposito, Miryam Ciotola, Maria Ida Maiorino, Roberto Gualdiero, Bruno Schisano, Antonio Ceriello, Flora Beneduce, Giovanni Feola, and Dario Giugliano.
• Second University of Naples and Azienda Sanitaria Locale Napoli 5, Naples, Italy.
• Ann. Intern. Med. 2008 Oct 21;149(8):531-9.

BackgroundInjection of long-acting insulin at bedtime is a common therapeutic approach for patients with type 2 diabetes that is poorly controlled with oral regimens. Neutral protamine lispro (NPL) insulin has demonstrated better glycemic control and similar incidence of hypoglycemic events than that of neutral protamine Hagedorn insulin.ObjectiveTo compare the clinical efficacy and safety of bedtime NPL insulin or insulin glargine in patients with type 2 diabetes who had suboptimal glycemic control while receiving stable doses of metformin and sulfonylurea.DesignOpen-label, randomized trial.SettingTeaching hospital (Azienda Ospedaliera Universitaria, Second University of Naples), Naples, Italy.Patients116 adults receiving stable doses of metformin plus sulfonylurea for longer than 90 days with hemoglobin A(1c) (HbA(1c)) levels of 7.5% to 10% and fasting plasma glucose levels of 6.7 mmol/L or greater (> or =120 mg/dL).Intervention10 IU of NPL insulin or insulin glargine injected subcutaneously at bedtime with weekly dose titrations to target fasting glucose levels less than 5.6 mmol/L (<100 mg/dL) in addition to stable oral regimens. Patients receiving nighttime sulfonylurea before the study were switched to metformin.MeasurementsThe primary outcome was change in HbA(1c) levels from baseline to week 36. Secondary outcomes were HbA(1c) levels less than 7%, self-reported hypoglycemic episodes, insulin dose, self-monitored glucose level, and body weight. Twenty patients in each group had continuous glucose monitoring for 3 consecutive days before adding insulin and at week 36.ResultsImprovement in HbA(1c) levels was similar in both groups (1.83% and 1.89% for NPL and glargine, respectively). The difference between the groups was 0.06 percentage point (95% CI, -0.1 to 0.15 percentage points). Secondary outcomes did not differ between groups. Hemoglobin A(1c) levels less than 7% occurred in 62% of patients receiving NPL and 64% of patients receiving glargine (difference, 2.0 percentage points [CI, -1.1 to 5.0 percentage points]). Fasting plasma glucose levels less than 5.6 mmol/L (<100 mg/dL) occurred in 40% of patients receiving NPL and 41% of patients receiving glargine (difference, 1.0 percentage point [CI, -0.9 to 3.0 percentage points]). Any hypoglycemic event occurred in 74% of patients receiving NPL and 67% of patients receiving glargine (difference, 7 percentage points [CI, -5 to 13 percentage points]). Continuous glucose level monitoring in the patients who had this measurement did not differ statistically.LimitationThe study was not blinded, had limited power to detect differences in hypoglycemic events, and did not obtain continuous glucose level monitoring for all patients.ConclusionSimilar glycemic control occurred with the addition of NPL or glargine insulin to oral regimens in patients with poorly controlled type 2 diabetes. Hypoglycemia was similar in the 2 groups, but sample size limited the ability to make a definite safety assessment.

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