Effects of pioglitazone in combination with metformin or a sulfonylurea compared to a fixed-dose combination of metformin and glibenclamide in patients with type 2 diabetes.
BACKGROUND
This study was designed to compare the effectiveness of co-administration of pioglitazone with metformin or a sulfonylurea (SU), with a fixed-dose combination of metformin and glibenclamide on glycemic control and beta-cell function in patients with type 2 diabetes.


METHODS
Patients (n = 250) treated with metformin (<or=3 g/day) or an SU as monotherapy for >3 months and with glycosylated hemoglobin (HbA(1c)) between 7.5% and 11% inclusive were randomized to receive either pioglitazone (15-30 mg/day) as add-on therapy to metformin or an SU or a fixed-dose combination of metformin (400 mg) and glibenclamide (2.5 mg) (up to three tablets per day) for 6 months. HbA(1c) and fasting plasma glucose (FPG) were measured at baseline and 2, 4, and 6 months. C-peptide levels were measured at baseline and 6 months, and post-challenge glucose and insulin responses were measured.


RESULTS
After 6 months, pioglitazone-based and fixed-dose metformin + glibenclamide resulted in similar reductions in HbA(1c) (-1.11% vs. -1.29%, respectively; P = 0.192) and FPG (-2.13 vs. -1.81 mmol/L, respectively; P = 0.370). Patients treated with pioglitazone for 6 months had significantly reduced C-peptide levels compared with baseline (-0.09 nmol/L, P = 0.001), while patients receiving fixed-dose metformin + glibenclamide combination had slightly increased C-peptide levels (+0.04 nmol/L, P = 0.08). Pioglitazone treatment also improved post-challenge insulin responses.


CONCLUSIONS
Co-administration of pioglitazone with metformin or an SU is an effective alternative to fixed-dose metformin + glibenclamide combination for patients with type 2 diabetes. The complementary effects of pioglitazone with either metformin or an SU may also have the potential to preserve beta-cell function and delay the progression of type 2 diabetes.
Comaschi
M
M
Emergency Department, University Hospital St. Martin, Genoa, Italy. Marco.Comaschi@hsanmartino.it
Demicheli
A
A
Di Pietro
C
C
Bellatreccia
A
A
Mariz
S
S
D000328:Adult; D002096:C-Peptide / Q000097:blood; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000188:drug therapy*; D004359:Drug Therapy, Combination; D005260:Female; D005905:Glyburide / Q000627:therapeutic use*; D006442:Glycated Hemoglobin / Q000378:metabolism; D006801:Humans; D007004:Hypoglycemic Agents / Q000627:therapeutic use; D050417:Insulin-Secreting Cells / Q000187:drug effects / Q000502:physiology; D008297:Male; D008687:Metformin / Q000627:therapeutic use*; D000077205:Pioglitazone; D012449:Safety; D045162:Thiazolidinediones / Q000627:therapeutic use*
D002096:C-Peptide; D005905:Glyburide; D006442:Glycated Hemoglobin; D007004:Hypoglycemic Agents; D008687:Metformin; D000077205:Pioglitazone; D045162:Thiazolidinediones