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Randomized Controlled Trial
. 2011 Jan;34(1):27-33.
doi: 10.2337/dc10-0531. Epub 2010 Oct 7.

Pharmacological treatment of the pathogenetic defects in type 2 diabetes: the randomized multicenter South Danish Diabetes Study

Jeppe Gram  1 , Jan Erik Henriksen, Ellen Grodum, Henning Juhl, Tony Bill Hansen, Christian Christiansen, Knud Yderstræde, Hans Gjessing, Henrik M Hansen, Vibe Vestergaard, Jørgen Hangaard, Henning Beck-Nielsen
Affiliations
Randomized Controlled Trial

Pharmacological treatment of the pathogenetic defects in type 2 diabetes: the randomized multicenter South Danish Diabetes Study

Jeppe Gram et al. Diabetes Care. 2011 Jan.

Abstract

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 and methods: 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 (rosiglitazone, 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%, P < 0.001). Aspart was associated with a higher increase in body weight (1.6 ± 0.6 kg, P < 0.01) and higher incidence of mild daytime hypoglycemia (4.9 ± 7.5 vs. 1.7 ± 5.4 number/person/year, P < 0.001) compared with NPH.

Conclusions: Insulin treatment of postprandial hyperglycemia results in lower A1C than treatment of fasting hyperglycemia, at the expense of higher body weight and hypoglycemic episodes. However, insulin therapy has to be combined with treatment of both peripheral and liver insulin resistance to normalize blood glucose, and in this case, the insulin regimen is less important.

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Figures

Figure 1
Figure 1
Enrollment and outcomes. The number of participants enrolled in the study is shown. The intention-to-treat (ITT) population included 369 patients, since 2 were withdrawn before first efficacy evaluation. The per-protocol population included 251 patients. asp, aspart.
Figure 2
Figure 2
Mean ± SE observed A1C values during the 2-year intervention period in patients randomized to treatment with either NPH insulin (black symbols) or insulin aspart (open symbols) in combination with placebo (A, P < 0.001), metformin (B, P = 0.15), rosiglitazone (C, P < 0.02), or metformin and rosiglitazone (D, P = 0.15).
See this image and copyright information in PMC

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