Effects of pioglitazone versus glipizide on body fat distribution, body water content, and hemodynamics in type 2 diabetes.
OBJECTIVE
Pioglitazone, a peroxisome proliferator-activated receptor agonist and glipizide, an insulin secretagogue, are commonly used to treat type 2 diabetes. Our study was designed to examine the effects of pioglitazone versus glipizide on body water, body composition, and hemodynamic parameters in the presence of comparable glycemic control between groups.


METHODS
We studied 19 diabetic subjects randomly assigned to either 45 mg pioglitazone (n = 8) or 10 mg (median dose) glipizide (n = 11) for 12 weeks. Body water content was measured with deuterated water, body composition by dual-energy X-ray absorptiometry and computed tomography, and cardiac output and systemic vascular resistance by acetylene rebreathing technique both before and after therapy.


RESULTS
Pioglitazone increased (P < 0.001 from baseline) total body water (+2.4 +/- 0.5 l) accounting for 75% of the total weight gain (+3.1 +/- 2.0 kg) but did not alter vascular endothelial growth factor concentrations. Total abdominal (-32.2 +/- 19 cm(2)) and visceral fat area (-16.1 +/- 8 cm(2)) tended to decrease with pioglitazone but increased (P < 0.02 for differences between groups) with glipizide (+38.4 +/- 17 cm(2) abdominal; +19.1 +/- 9 cm(2) visceral). Pioglitazone tended to reduce (P = 0.05) diastolic (-8.4 +/- 4 mmHg) and mean (-9.5 +/- 5 mmHg; P = 0.08) blood pressure and reduced (P < 0.001) systemic vascular resistance (2,785 +/- 336 vs. 2,227 +/- 136 dynes/s per m(2)), while there were no differences in these parameters with glipizide. Neither therapy altered circulating catecholamine concentrations.


CONCLUSIONS
When pioglitazone and glipizide are given in doses sufficient to achieve equivalent glycemic control in people with type 2 diabetes, pioglitazone increases total body water, thereby accounting for the majority of weight gain, tended to decrease visceral and abdominal fat content and blood pressure, and reduces systemic vascular resistance.
Basu
Ananda
A
Division of Endocrinology and Metabolism, 200 First Street SW, Rochester, MN 55905, USA. basu.ananda@mayo.edu
Jensen
Michael D
MD
McCann
Frances
F
Mukhopadhyay
Debabrata
D
Joyner
Michael J
MJ
Rizza
Robert A
RA
D000328:Adult; D000368:Aged; D001786:Blood Glucose / Q000378:metabolism; D001823:Body Composition; D050218:Body Fat Distribution; D001834:Body Water / Q000378:metabolism*; D003924:Diabetes Mellitus, Type 2; D005260:Female; D005913:Glipizide / Q000627:therapeutic use*; D006442:Glycated Hemoglobin / Q000378:metabolism; D006439:Hemodynamics / Q000187:drug effects*; D006801:Humans; D007004:Hypoglycemic Agents / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D000077205:Pioglitazone; D045162:Thiazolidinediones / Q000627:therapeutic use*; D042461:Vascular Endothelial Growth Factor A / Q000097:blood
D001786:Blood Glucose; D005913:Glipizide; D006442:Glycated Hemoglobin; D007004:Hypoglycemic Agents; D000077205:Pioglitazone; D045162:Thiazolidinediones; D042461:Vascular Endothelial Growth Factor A; C467484:VEGFA protein, human