2-year effects of pioglitazone add-on to sulfonylurea or metformin on oral glucose tolerance in patients with type 2 diabetes.
OBJECTIVE
We report the effectiveness of the thiazolidinedione, pioglitazone, as add-on medication to metformin or sulfonylurea in reducing post-load serum glucose levels, as assessed by 3-h oral glucose tolerance testing (OGTT).


METHODS
Adult patients with Type 2 diabetes took part in one of two large-scale, 2-year clinical trials. One study compared pioglitazone treatment as add-on to failing metformin therapy (N=317) with add-on gliclazide treatment to metformin (N=313). The other study compared combination therapy with pioglitazone added to existing failing sulfonylurea therapy (N=319) with metformin treatment in addition to sulfonylurea (N=320). HbA(1c) and fasting plasma glucose concentrations were measured at baseline and throughout the study and at the final visit at week 104. At selected centers (N=299 patients), a 3-h OGTT was performed at baseline and at week 104.


RESULTS
At week 104, mean HbA(1c) reduction from baseline was 0.89% for pioglitazone and 0.77% for gliclazide addition to metformin (p=0.200) and 1.03% with pioglitazone and 1.16% with metformin addition to sulfonylurea (p=0.173) in the total patient cohort. In the 299 patients who underwent OGTT, 2 years of treatment with pioglitazone, whether added to existing metformin or sulfonylurea medication, resulted in decreases in glucose excursions after an oral glucose load without increasing post-load serum insulin concentrations. In contrast, gliclazide in combination with metformin therapy caused increases in both post-load serum glucose and insulin excursions after 2 years, whereas metformin add-on to sulfonylurea did not have a significant effect on post-load serum glucose concentrations and resulted in an increase in insulin levels.


CONCLUSIONS
There were no significant differences in HbA(1c) levels between groups. However, 2-year treatment with pioglitazone as an add-on to either failing metformin or sulfonylurea therapy improved post-load glucose excursions without affecting insulin secretion. In contrast, glucose excursions were not improved by gliclazide or metformin add-on therapy, despite increases in post-load insulin levels. These data suggest that pioglitazone reduces peripheral insulin resistance via mechanisms different from those of metformin.
Seufert
Jochen
J
Division of Endocrinology and Diabetology, Department of Internal Medicine II, University Hospital of Freiburg, Hugstetter Strasse 55, 79106 Freiburg, Germany. jochen.seufert@uniklinik-freiburg.de
Urquhart
Richard
R
D000328:Adult; D000368:Aged; D001786:Blood Glucose / Q000378:metabolism; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000188:drug therapy*; D004359:Drug Therapy, Combination; D005260:Female; D005951:Glucose Tolerance Test; D006442:Glycated Hemoglobin / Q000378:metabolism; D006801:Humans; D007004:Hypoglycemic Agents / Q000494:pharmacology / Q000627:therapeutic use; D008297:Male; D008687:Metformin / Q000627:therapeutic use*; D008875:Middle Aged; D000077205:Pioglitazone; D013453:Sulfonylurea Compounds / Q000627:therapeutic use*; D045162:Thiazolidinediones / Q000627:therapeutic use*
D001786:Blood Glucose; D006442:Glycated Hemoglobin; D007004:Hypoglycemic Agents; D008687:Metformin; D000077205:Pioglitazone; D013453:Sulfonylurea Compounds; D045162:Thiazolidinediones