Effects of troglitazone on insulin action and cardiovascular risk factors in patients with non‐insulin‐dependent diabetes
AM Sironi, S Vichi, A Gastaldelli… - Clinical …, 1997 - Wiley Online Library
Clinical Pharmacology & Therapeutics, 1997•Wiley Online Library
Objective Insulin resistance is a potential target for pharmacologic intervention in non‐
insulin‐dependent diabetes. Troglitazone is being evaluated as an insulin enhancer in
insulin resistant states. Research design and methods We randomized 40 patients with non‐
insulin‐dependent diabetes to diet plus placebo (n= 15) or diet plus troglitazone (n= 25; 200
mg/day) treatment for 8 weeks. Fasting endogenous glucose production (EGP, by the stable
isotope technique) and whole‐body insulin sensitivity (by the insulin suppression test) were …
insulin‐dependent diabetes. Troglitazone is being evaluated as an insulin enhancer in
insulin resistant states. Research design and methods We randomized 40 patients with non‐
insulin‐dependent diabetes to diet plus placebo (n= 15) or diet plus troglitazone (n= 25; 200
mg/day) treatment for 8 weeks. Fasting endogenous glucose production (EGP, by the stable
isotope technique) and whole‐body insulin sensitivity (by the insulin suppression test) were …
Objective
Insulin resistance is a potential target for pharmacologic intervention in non‐insulin‐dependent diabetes. Troglitazone is being evaluated as an insulin enhancer in insulin resistant states.
Research design and methods
We randomized 40 patients with non‐insulin‐dependent diabetes to diet plus placebo (n = 15) or diet plus troglitazone (n = 25; 200 mg/day) treatment for 8 weeks. Fasting endogenous glucose production (EGP, by the stable isotope technique) and whole‐body insulin sensitivity (by the insulin suppression test) were measured at baseline and on days 3, 7, 14, 28, and 56 of treatment.
Results
By day 56, fasting plasma glucose had risen from 12.0 ± 0.9 to 12.8 ± 1.2 mmol/L in the placebo group and had fallen from 12.4 ± 0.6 to 11.3 ± 0.6 mmol/L in the troglitazone group (p = 0.03). This was the result of small improvements in whole‐body insulin sensitivity (steady‐state plasma glucose during the insulin suppression test: from 11.09 ± 1.1 to 10.3 ± 0.8 mmol/L versus 13.8 ± 1.0 to 10.0 ± 0.9 mmol/L, placebo versus troglitazone; p = 0.01) and EGP (from 103% ± 3% versus 96% ± 2% of baseline, placebo versus troglitazone; p = 0.09). The time course of insulin action showed an early (first week of treatment) decrease in EGP in the troglitazone group that was maintained throughout, whereas steady‐state plasma glucose levels began to diverge toward the end of treatment. The effects of insulin on plasma free fatty acid and potassium concentrations were not different between placebo and troglitazone. The cardiovascular risk profile (heart rate; serum triglycerides; total, low‐density lipoprotein, and high‐density lipoprotein cholesterol; proinsulin; uric acid; plasminogen activator inhibitor‐1 antigen and activity; 24‐hour blood pressure monitoring; and urinary albumin excretion) was unaltered by troglitazone treatment.
Conclusions
Troglitazone as monotherapy for typical non‐insulin‐dependent diabetes had a modest anti‐hyperglycemic effect and, at the dose used in this study, had no effect on cardiovascular risk factors.
Clinical Pharmacology & Therapeutics (1997) 62, 194–202; doi:
Wiley Online Library