NEW YORK (Reuters Health) – In patients with type 2 diabetes who are poorly controlled on a sulfonylurea agent, the addition of troglitazone produces twice as great an effect on whole-body insulin action and glucose disposal as does the addition of metformin, US researchers report.
Senior investigator Dr. Robert R. Henry, of the VA San Diego Healthcare System in California, and colleagues assigned 21 type 2 diabetics who were failing maximal sulfonylurea therapy to use glyburide 10 mg b.i.d. instead of their existing drug. Four weeks later, the patients were randomized to start additional therapy with metformin, up to 2550 mg/day, or troglitazone, up to 600 mg/day.
After 3 to 4 months of combination therapy, the insulin-stimulated whole-body glucose disposal rate in the metformin group had improved significantly from baseline, by a mean of 20% (p < 0.05). But the mean improvement in the troglitazone group was even greater, 44% (p < 0.01 vs. baseline, p < 0.05 vs. metformin).
HbA1c levels were statistically similar in the two groups. This suggests that "factors other than changes in circulating glucose and insulin levels are responsible for the difference," the investigators write in the January edition of Diabetes.
One such factor, they propose, may be that troglitazone is better able than metformin to increase glucose uptake and insulin action in adipose tissue. Unlike metformin, troglitazone upregulated GLUT4 protein expression, insulin signaling, and glucose transport into adipocytes.
Dr. Henry and his associates add that "the relationship between increased glucose uptake in subcutaneous adipocytes and further improvements in whole-body glucose disposal, occurring in response to troglitazone and not metformin, also suggests that adipose tissue can make a major contribution to whole-body glucose disposal."
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