A comparison of troglitazone and metformin on insulin requirements in euglycemic intensively insulin-treated type 2 diabetic patients

• Published in: Diabetes (New York, N.Y.) Vol. 48; no. 12; pp. 2414 - 2421
• Main Authors: YU, J. G, KRUSZYNSKA, Y. T, MULFORD, M. I, OLEFSKY, J. M
• Format: Journal Article
• Language: English
• Published: Alexandria, VA American Diabetes Association 01-12-1999
• Subjects: Biological and medical sciences; Blood Glucose - metabolism; Body Weight - drug effects; C-Peptide - blood; Cholesterol - blood; Cholesterol, HDL - blood; Cholesterol, LDL - blood; Chromans - therapeutic use; Circadian Rhythm; Diabetes Mellitus, Type 2 - blood; Diabetes Mellitus, Type 2 - drug therapy; Diabetes Mellitus, Type 2 - physiopathology; Dose-Response Relationship, Drug; Drug therapy; Drug Therapy, Combination; Evaluation; Fatty Acids, Nonesterified - blood; Female; Fructosamine - blood; General and cellular metabolism. Vitamins; Humans; Hypoglycemic Agents - therapeutic use; Insulin - administration & dosage; Insulin - blood; Insulin - therapeutic use; Insulin Infusion Systems; Male; Medical sciences; Metformin; Metformin - therapeutic use; Middle Aged; Pharmacology. Drug treatments; Thiazoles - therapeutic use; Thiazolidinediones; Triglycerides - blood; Troglitazone; Type 2 diabetes; Endocrinopathy; Human; Pancreatic hormone; Non insulin dependent diabetes; Insulin; Biological activity; Chemotherapy; Hypoglycemic agent; Biguanides; Treatment; Metformin; Comparative study; Troglitazone
• ISSN: 0012-1797; 1939-327X
• DOI: 10.2337/diabetes.48.12.2414

A comparison of troglitazone and metformin on insulin requirements in euglycemic intensively insulin-treated type 2 diabetic
patients.
J G Yu ,
Y T Kruszynska ,
M I Mulford and
J M Olefsky
Department of Endocrinology and Metabolism, University of California San Diego, La Jolla 92093, USA.
Abstract
Troglitazone and metformin lower glucose levels in diabetic patients without increasing plasma insulin levels. We compared
the insulin sparing actions of these two agents and their effects on insulin sensitivity and insulin secretion in 20 type
2 diabetic patients. To avoid the confounding effect of improved glycemic control on insulin action and secretion, patients
were first rendered euglycemic with 4 weeks of continuous subcutaneous insulin infusion (CSII) before randomization to CSII
plus troglitazone (n = 10) or CSII plus metformin (n = 10); euglycemia was maintained for another 6-7 weeks. Insulin sensitivity
was assessed by a hyperinsulinemic-euglycemic clamp 1) at baseline, 2) after 4 weeks of CSII, and 3) after CSII plus either
troglitazone or metformin. The 24-h glucose, insulin, and C-peptide profiles were performed on the day before the second and
third glucose clamps. Good glycemic control was achieved with CSII alone and was maintained with CSII plus an oral agent (mean
24-h glucose: troglitazone, 6.2+/-0.6 mmol/l; metformin, 6.2 +/-0.3 mmol/l). Insulin requirements decreased 53% with troglitazone
compared with CSII alone (48+/-4 vs. 102+/-13 U/day, P < 0.001), but only 31% with metformin (76+/-13 vs. 110+/-18 U/day,
P < 0.005). The 24-h C-peptide profiles were similar. Normal fasting hepatic glucose output was maintained with both agents
despite lower insulin levels than on CSII alone. Insulin sensitivity did not change significantly with CSII alone or with
CSII plus metformin, but improved 29% with CSII plus troglitazone (P < 0.005 vs. CSII alone) and was then 45% higher than
in the CSII plus metformin patients (P < 0.005). In conclusion, metformin has no effect on insulin-stimulated glucose disposal
independent of glycemic control in type 2 diabetes. Troglitazone (600 mg/day) has greater insulin-sparing effects than metformin
(1,700 mg/day) in CSII-treated euglycemic patients. This is probably explained by the peripheral tissue insulin-sensitizing
effects of troglitazone.