OBJECTIVE- To characterize metabolic effects of troglitazone in type 2 diab
etic, obese, and lean subjects, and examine the effects of troglitazone 2-3
weeks after discontinuation.
RESEARCH DESIGN AND METHODS- Nine type 2 diabetic, nine obese, and nine lea
n subjects underwent baseline metabolic studies including an 8-h meal-toler
ance test (MTI) and a 5-h glucose clamp. Subjects then received troglitazon
e (600 mg/day) for 12 weeks and subsequently had repeat metabolic studies.
Diabetic subjects remained off hypoglycemic agents for 2-3 weeks and then u
nderwent a 5-h glucose clamp.
RESULTS- In diabetic subjects, fasting plasma glucose was reduced (P < 0.05
) and insulin-stimulated glucose disposal (R-d) was enhanced by treatment (
P < 0.02). The area under the MTT 8-h plasma glucose curve declined with th
erapy (P < 0.001), and its change was positively correlated with the improv
ement in R-d (r = 0.75, P < 0.05). There was also a positive correlation be
tween the change in fasting hepatic glucose output (HGO) and the change in
fasting plasma glucose with treatment (r = 0.92, P < 0.001). Discontinuatio
n of therapy for 2-3 weeks did not significantly affect fasting plasma gluc
ose or insulin-stimulated glucose R-d. In obese subjects, insulin-stimulate
d glucose R-d improved with therapy (P < 0.001), allowing for maintenance o
f euglycemia by lower plasma insulin concentrations (P < 0.05). In lean sub
jects, an increase in fasting HGO (P < 0.001) and glucose clearance (P < 0.
01) was observed.
CONCLUSIONS- Troglitazone lowers fasting and postprandial plasma glucose in
type 2 diabetes by affecting both fasting HGO and peripheral insulin sensi
tivity. Its effects are evident 2-3 weeks after discontinuation. In obese s
ubjects, its insulin sensitizing effects suggest a role for its use in the
primary prevention of type 2 diabetes.