Troglitazone add-on therapy to a combination of sulfonylureas plus metformin achieved and sustained effective...

To elucidate the effect of triple combination oral agent therapy on type 2 diabetes.

We performed a prospective longitudinal study on 40 patients with type 2 diabetes who had failed to achieve a glycosylated hemoglobin (HbA1c) of < or = 8.0% despite optimal therapy with a combination of sulfonylureas plus metformin. Troglitazone was added and then titrated, with the intent to achieve at least a 1% reduction in HbA1c within 3 months. Responders were reassessed at 6 and 12 months. Nonresponders were reassessed at 6 months; in the absence of a significant HbA1c response, participation in the study was discontinued.

Of the 40 study subjects, 25 were responders, 10 were nonresponders, and 5 were withdrawn from the study before completion of 3 months of therapy because of side effects. The 25 responders had a mean baseline HbA1c of 9.9%, which decreased significantly to 7.8% after 3 months of troglitazone therapy and to 7.4% at 6 months and at 12 months. In addition, the fasting blood glucose (FBG) in the responders decreased significantly from 168 mg/dL at baseline to 118 mg/dL at 6 months, which was sustained at 121 mg/dL at 12 months. In the responder group, a mean HbA1c < or = 8% was achieved in 68% at 6 months and sustained in 65% after 1 year. Furthermore, 40% of responders achieved a mean HbA1c < or = 7.0% at 6 months, and 39% sustained this degree of control at 12 months. The 10 nonresponders showed no significant change in HbA1c or FBG during the 6 months of troglitazone therapy. No difference existed in the mean baseline FBG, HbA1c, or C peptide level between the two groups. Responders, however, had a significantly lower mean body mass index (BMI) (31 kg/m2) than did nonresponders (37 kg/m2). Although responders were older than nonresponders (mean age, 65 years versus 55 years), no significant difference was noted in duration of diabetes (11.6 years versus 8.7 years). Multivariate analysis showed that male gender and BMI were the strongest predictors of a response to troglitazone add-on therapy to the prior combination of sulfonylureas plus metformin.

This study showed that oral therapy with troglitazone added to sulfonylureas plus metformin achieved and sustained a significant improvement in control of diabetes in 71% of patients who had failed to achieve HbA1c < or = 8% with dual oral agent therapy. The positive response was evident within 3 months, reached maximum by 6 months, and was sustained to 12 months of therapy. Therefore, patients who fail to achieve HbA1c < or = 8% with sulfonylureas plus metformin should have at least 3 months of troglitazone add-on therapy before advancing to traditional insulin treatment.