Insulin lispro in the treatment of patients with type 2 diabetes mellitus after oral agent failure

This study assessed the safety profile and efficacy of a new combination therapy (insulin lispro plus sulfonylurea) in patients with type 2 diabetes mellitus experiencing secondary oral agent failure. A total of 423 patients were randomly assigned to 3 treatment groups: preprandial insulin lispro plus sulfonylurea (L + S), bedtime neutral protamine Hagedorn (NPH) insulin plus sulfonylurea (N + S), and preprandial insulin Lispro plus bedtime NPH insulin (L + N). Mean decreases in glycosylated hemoglobin from baseline were 1.60% +/- 1.27% for patients receiving L + S, 1.21% +/- 1.21% for those receiving N + S, and 1.40% +/- 1.46% for those receiving L + N (within treatment, P < 0.001; for L + S vs N + S, P = 0.003). Fasting blood glucose level was higher in patients receiving L + S (171 +/- 46.5 mg/dL) or L + N (166 +/- 52.5 mg/dL) than in those receiving N + S (144 +/- 48.2 mg/dL) (P < 0.001, for both comparisons). Conversely, postprandial blood glucose level was lower in patients receiving L + S (165 +/- 41.6 mg/dL) or L + N (165 +/- 46.3 mg/dL) than in those receiving N + S (213 +/- 58.3 mg/dL) (P < 0.001, for both comparisons). The overall rate of hypoglycemia (episodes per 30 days) was not statistically significant when the L + S, N + S, and L + N therapies were compared (0.99 +/- 1.74 vs 0.87 +/- 2.31 vs 1.16 +/- 2.38, respectively). The rate of nocturnal hypoglycemia was lowest in the L + S group (0.00 +/- 0.00 vs 0.10 +/- 0.37 for the N + S group vs 0.15 +/- 0.54 for the L + N group; P = 0.004). L + S, which has a safety profile equal to those of N + S and L + N, is an effective treatment for patients with type 2 diabetes who experience oral sulfonylurea agent failure. L + S offers an alternative to these established combination therapies in patients whose type 2 diabetes cannot be controlled with a sulfonylurea alone.