Pharmacological Treatment of the Pathogenetic Defects in Type 2 Diabetes The randomized multicenter South Danish Diabetes Study

OBJECTIVE — To determine the effect of treatment with insulin aspart compared with NPH insulin, together with metformin/placebo and rosiglitazone/placebo. The hypothesis was that combined correction of major pathogenetic defects in type 2 diabetes would result in optimal glycemic control. RESEARCH DESIGN ANDMETHODS — This study was a 2-year investigator-driven randomized partly placebo-controlled multicenter trial in 371 patients with type 2 diabetes on at least oral antiglycemic treatment. Patients were assigned to one of eight treatment groups in a factorial design with insulin aspart at mealtimes versus NPH insulin once daily at bedtime, metformin twice daily versus placebo, and rosiglitazone twice daily versus placebo. The main outcome measurement was change in A1C. RESULTS — A1C decreased more in patients treated with insulin aspart compared with NPH (0.41 0.10%, P 0.001). Metformin decreased A1C compared with placebo (0.60 0.10%, P 0.001), as did rosiglitazone (0.55 0.10%, P 0.001). Triple therapy (rosigli-tazone, metformin, and any insulin) resulted in a greater reduction in A1C than rosiglitazone plus insulin (0.50 0.14%, P 0.001) and metformin plus insulin (0.45 0.14%,