A comparison in a clinical setting of the efficacy and side effects of three thiazolidinediones.
Authors: A B King
Journal: Diabetes Care (2000)

A Comparison in a Clinical Setting of the Efficacy and Side Effects of Thre e T h i a z o l i d i n e d i o n e sT h ree thiazolidinediones (TZDs) are c u rrently available for clinical use in the U.S.: troglitazone, ro s i g l i t a z o n e , and pioglitazone.Because we are aware of no comparative studies of these thre e agents, we wish to re p o rt our initial experience with their efficacy in lowering glucose and improving dyslipidemia, as well as their side eff e c t s .When clinically indicated, patients were started consecutively on each of the three TZDs as they became available.Results from the TZD groups, each of which comprised 50 patients, were reviewed.We excluded patients who w e re not on maximal re c o m m e n d e d doses of TZDs; namely, 600 mg of troglitazone, 8 mg of rosiglitazone (twice a day for monotherapy), and 45 mg of pioglitazone.Patients were also excluded if they started during the observation period on a medication that would influence their lipid profile or weight.Only data at baseline and between 2 and 4 months of treatment were analyzed.After exclusion, the total numbers of patients in each group, tro g l i t a z o n e , rosiglitazone, and pioglitazone were 35, 36, and 30, re s p e c t i v e l y.Their average ages were 60.1, 59.2, and 60.2 years; sex, 65, 50, and 38% male to total patients; weight, 89.7, 92.1, and 87.2 kg; and initial HbA 1 c , 8.50, 8.73, and 8.72%.Patients were taking other medications for h y p e rglycemia treatment in 89, 76, and 81% of each gro u p .Table 1 compares the effect of each TZD.HbA 1 c was similarly reduced with each agent, especially when patients with an initial HbA 1 c 7.9% were studied.The magnitude of reduction re p o rted is g reater than that re p o rted elsewhere (1) and may re flect the self-education and self-monitoring of blood glucose that is p a rt of our pro g r a m .We observed that the beneficial eff e c t on lipids was most with pioglitazone and least with rosiglitazone during this 2-to 4 -month observation period.The average initial HDL cholesterol in each gro u p , n a m e l y, troglitazone, rosiglitazone, and pioglitazone was 46.6, 43.1, and 50.7 mg/dl, respectively; LDL cholesterol was 109.1, 102.9, and 96.4 mg/dl, re s p e c t i v e l y ; and the triglycerides were 223, 172, and 207 mg/dl, re s p e c t i v e l y.The lack of eff e c t of rosiglitazone on triglycerides and the elevation of LDL cholesterol (2) and the b e n e ficial effect on HDL and triglycerides of pioglitazone (3) have been pre v i o u s l y re p o rt e d .In addition, the weight incre a s e with pioglitazone was noticeably gre a t e r than that observed with the other two agents.However, the incidence of edema as the reason for discontinuing a medication was not greater with pioglitazone than with rosiglitazone.The weight gain cannot be explained on i m p rovement of glucose control since all agents reduced the HbA 1 c e q u a l l y.P e rhaps the increase in weight is due to the increase in the number and size of adipocytes (4).We conclude from our observ a t i o n s that each TZD appears equal in its glucose lowering ability, and thus, the selection of an agent is based on other factors, such as its lipid benefit and side e ffects.We look forw a rd to larger and l o n g e r-t e rm studies to confirm this fin ding and to compare the liver toxicity of each agent.