Classification of type 2 diabetes by clinical response to metformin-troglitazone combination and C-Peptide criteria.
OBJECTIVE
To assess the ability of basal and stimulated C-peptide levels and stimulated glucose values after oral administration of glucose to predict a successful response to metformin and troglitazone combination therapy after discontinuation of insulin therapy.


METHODS
At the onset of the study, plasma glucose and C-peptide levels were measured in a group of 64 obese patients with insulin-treated type 2 diabetes while they were fasting and 2 hours after a challenge of 100 g of glucose administered orally. Then combination metformin-troglitazone treatment was initiated while insulin therapy was gradually tapered over 8 to 12 weeks. Subjects who successfully tolerated insulin withdrawal after the metformin-troglitazone combination were categorized as non-insulin-requiring responders, whereas those who needed insulin to obtain glycemic control were categorized as insulin-requiring nonresponders. Basal and glucose-stimulated C-peptide levels as well as stimulated glucose values were contrasted in the responder versus nonresponder groups. In a second protocol, eight obese patients with insulin-treated type 2 diabetes who successfully stopped insulin therapy were reassessed for C-peptide and glucose variables during the 2-hour oral glucose tolerance test. This reassessment followed a 12-week period of therapy to determine whether treatment of insulin resistance with the combination of metformin and troglitazone could normalize the impaired glucose tolerance in type 2 diabetes.


RESULTS
After metformin-troglitazone therapy, 48 study subjects (75%) could later be managed without insulin, whereas 16 (25%) needed insulin to achieve acceptable glycemic control. In a comparison of the non-insulin-requiring responder and insulin-requiring nonresponder groups, the responder group had significantly higher glucose-stimulated C-peptide levels and much lower stimulated glucose levels. The mean basal plasma C-peptide level was higher in the responder than in the nonresponder group, but a small degree of overlap was found between the two groups. Combination treatment with metformin and troglitazone for 12 weeks resulted in a significant reduction in the C-peptide response and glucose variables after the glucose load.


CONCLUSIONS
The results of this study indicate that stimulated C-peptide and glucose levels may be useful criteria to identify whether combination metformin-troglitazone treatment can successfully replace insulin therapy in the management of obese patients with type 2 diabetes. Inability to normalize glucose intolerance after restoring insulin resistance with insulin sensitizers is supportive of the presence of both disturbed beta-cell function and insulin resistance in patients with type 2 diabetes.
Lee
A
A
Department of Medicine, St. Louis University Medical Center, St. Louis, Missouri, USA.
Morley
J
J