A Randomized, Placebo-Controlled Trial Assessing the Effects of Rosiglitazone on Echocardiographic Function and Cardiac Status in Type 2 Diabetic Patients With New York Heart Association Functional Class I or II Heart Failure

Abstract

This study investigated the effects of rosiglitazone (RSG) on left ventricular ejection fraction (LVEF) in subjects with type 2 diabetes (T2DM) and pre-existing chronic heart failure (CHF) (New York Heart Association [NYHA] functional class I to II). Fluid retention is an important consideration in the use of thiazolidinediones in T2DM patients because it could exacerbate symptoms or precipitate decompensation in those with previously stable CHF. A total of 224 patients with T2DM and NYHA functional class I to II CHF with LVEF < or =45% were randomized to a 52-week treatment with RSG (4 to 8 mg daily, n = 110) or placebo (PLB) (n = 114) in addition to background antidiabetes therapy. Treatment was uptitrated to achieve target fasting plasma glucose <126 mg/dl; CHF medications were adjusted as appropriate. The LVEF was similar in both groups at baseline (RSG 35.3 +/- 6.2%, PLB 35.7 +/- 7.8%) and after 52 weeks of treatment (mean difference 1.49%, p = 0.1). Glycemic control was significantly better in the RSG group (mean difference in hemoglobin A1c -0.65%, p < 0.0001). There were significantly more adjudicated events in the RSG group of new or worsening edema (RSG n = 28 [25.5%]; PLB n = 10 [8.8%]; p = 0.005) and increased CHF medication (RSG n = 36 [32.7%], PLB n = 20 [17.5%]; p = 0.037), but no significant difference between groups for other adjudicated end points. A similar proportion of patients withdrew from each treatment group because of adverse events. After 52 weeks of treatment, RSG improved glycemic control but did not adversely affect LVEF in patients with T2DM and NYHA functional class I to II CHF. More fluid-related events occurred with RSG, although these generally did not lead to withdrawal from the study.