CARDIAC AND GLYCEMIC BENEFITS OF TROGLITAZONE TREATMENT IN NIDDM

Troglitazone is a thiazolidinedione under development for the treatmen t of NIDDM and potentially other insulin-resistant disease states, Tre atment with troglitazone is associated with an improvement in hypergly cemia, hyperinsulinemia, and insulin-mediated glucose disposal, No sig nificant side effects have been observed in humans, Because of reporte d cardiac changes in animals treated with drugs of this class, this mu lticenter 48-week study was conducted to evaluate whether NIDDM patien ts treated with troglitazone develop any cardiac mass increase or func tional impairment, A total of 154 NIDDM patients were randomized to re ceive troglitazone 800 mg q.d, or glyburide titrated to achieve glycem ic control (less than or equal to 20 mg b,i.d, or q.d.). Two-dimension al echocardiography and pulsed Doppler were used to measure left ventr icular mass index (LVMI), cardiac index (CI), and stroke volume index (SVI), All echocardiograms were performed at each center (baseline, 12 , 24, 36, and 48 weeks), recorded on videotape, and forwarded to a bli nded central echocardiographic interpreter for analysis, The results s howed that LVMI of patients treated with troglitazone was not statisti cally or clinically different from baseline after 24 or 48 weeks, Stat istically significant increases in SVI and CI and a statistically sign ificant decrease in diastolic pressure and estimated peripheral resist ance were observed in troglitazone-treated patients. These results wer e not sex-specific, Glycemic benefits of troglitazone treatment were o bserved as evidenced by long-term improvement of HbA(1c) and C-peptide levels. Furthermore, triglycerides were significantly lower, and HDL was significantly higher at weeks 24 and 48, In conclusion, NIDDM pati ents treated with troglitazone do not show any cardiac mass increase o r cardiac function impairment, Conversely, patients on troglitazone be nefited from enhanced cardiac output and stroke volume, possibly as a result of decreased peripheral resistance, Treatment with troglitazone appears to have a favorable impact on known cardiovascular risk facto rs and could potentially lower cardiovascular morbidity in NIDDM patie nts.