Effect of Early Thiazolidinedione Therapy on A1C Levels
Durbin conducted a prospective analysis of a multiethnic population with impaired glucose tolerance (IGT) and insulin resistance (IR) to determine whether thiazolidinedione treatment can delay the onset of type 2 diabetes. Eligible patients had normal or borderline A1C, elevated C-peptide levels (>2 mg/mL), fasting blood glucose (FPG) levels between 100 and 125 mg/dL, and 2-hour postprandial blood glucose levels between 140 and 200 mg/dL.
A total of 172 patients (aged 29-86 years) were enrolled in the study, with 101 patients initially receiving troglitazone 400 mg/day. During the course of the study, troglitazone was withdrawn from the US market because of safety concerns (March 2000) and patients in the study were randomly switched to either rosiglitazone (n=39) or pioglitazone (n=62). A group of 71 patients that had IGT and IR received no antidiabetic treatment and served as the control group. There were no significant differences between treatment and control groups in gender, age, or ethnicity.
Starting dosages were rosiglitazone 4 mg/day and pioglitazone 30 mg/day, although several patients were titrated to high dosages. Mean duration of treatment was 36 months (range: 24 to 45 months), with patients initially spending a mean of 10 months on troglitazone (range: 3 to 27 months). Other medications such as antihypertensives and antihyperlipidemic agents were prescribed as needed to meet the National Cholesterol Education Program Adult Treatment Panel III guidelines, but no additional oral antidiabetic agents were used.
Shown are the mean A1C levels during the course of the study. Although A1C levels are not considered an early screening tool, these values are recognized as effective measures of glycemic index. Patients treated with thiazolidinediones showed significant improvement in A1C levels from baseline (P<0.001). Overall, there was a significant difference in mean reduction of A1C levels between the rosiglitazone and pioglitazone groups vs the control group (P<0.001). At the end of the study, the control group experienced an increase of 0.52% in A1C levels from baseline (P<0.001).
Three patients in the thiazolidinedione treatment groups progressed to type 2 diabetes by the end of the study, compared with 19 patients in the control group. The incidence of diabetes after 3 years was 88.9% lower in the rosiglitazone and pioglitazone groups compared with the control group (P<0.001). These findings support the theory that rosiglitazone or pioglitazone treatment may be used as an early presymptomatic treatment for individuals at risk of developing type 2 diabetes.
