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

J Am Coll Cardiol. 2007 Apr 24;49(16):1696-704. doi: 10.1016/j.jacc.2006.10.077. Epub 2007 Apr 6.


Objectives: 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).

Background: 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.

Methods: 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.

Results: 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.

Conclusions: 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.

Publication types

  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Cardiac Output, Low / drug therapy*
  • Diabetes Mellitus, Type 2 / drug therapy*
  • Double-Blind Method
  • Echocardiography / drug effects
  • Female
  • Humans
  • Hypoglycemic Agents / adverse effects
  • Hypoglycemic Agents / therapeutic use*
  • Male
  • Middle Aged
  • Rosiglitazone
  • Thiazolidinediones / adverse effects
  • Thiazolidinediones / therapeutic use*
  • Ventricular Function, Left / drug effects*
  • Water-Electrolyte Balance / drug effects


  • Hypoglycemic Agents
  • Thiazolidinediones
  • Rosiglitazone