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Study Objective: To compare the relative efficacy, risks, and benefits of insulin with glyburide in achieving normoglycemia in non-insulin-dependent diabetes mellitus., Design: Randomized, double-blind, placebo-controlled trial with a 9-month treatment period., Setting: University hospital., Patients: Thirty-one patients with non-insulin-dependent diabetes mellitus who did not have normal glucose control with diet alone., Interventions: Once-per-day NPH insulin and placebo glyburide, or glyburide and once-per-day placebo insulin injection. Active drug and placebo adjusted in parallel to achieve fasting plasma glucose level less than 6.4 mmol/L (115 mg/dL) without hypoglycemia., Measurements and Main Results: Insulin and glyburide produced similar improvement in fasting blood glucose levels and hemoglobin A1c concentrations, similar frequencies of mild symptomatic hypoglycemia, and similar weight gain despite dietary reinforcement. Triglyceride and cholesterol levels decreased and high-density lipoprotein cholesterol and ratios of high-density lipoprotein to total cholesterol increased in both groups, with a significantly greater improvement in high-density lipoprotein cholesterol and ratio of high-density lipoprotein total cholesterol in patients treated with insulin., Conclusions: Therapy with glyburide or once-per-day NPH insulin provides a similar degree of glucose control in patients with non-insulin-dependent diabetes mellitus. Insulin may have a relative advantage in that it is associated with higher levels of high-density lipoprotein cholesterol and a higher ratio of high-density lipoprotein to total cholesterol.

A suitable placebo for NPH insulin has not previously been available for clinical investigation. A series of organic and inorganic compounds were formulated as insulin placebos and analyzed according to the following criteria: (1) degree of visual similarity to insulin, (2) stability, (3) absence of local side effects, and (4) clinical safety. Dilute suspensions of cortisone acetate (1.25-2.5 mg/ml) were found to fulfill the criteria as acceptable insulin placebos. Placebo-controlled studies with NPH insulin can now be performed.