Fluid retention after initiation of thiazolidinedione therapy in diabetic patients with established chronic heart failure

J Am Coll Cardiol. 2003 Apr 16;41(8):1394-8. doi: 10.1016/s0735-1097(03)00159-1.


Objectives: We sought to define the characteristics of fluid retention after thiazolidinedione (TZD) initiation in patients with established heart failure (HF).

Background: Fluid retention associated with the use of TZD is commonly attributed to exacerbation of HF, which has led to the proscription of these potentially useful agents in patients with chronic HF.

Methods: We examined 111 consecutive diabetic patients with chronic systolic HF who were treated with TZD from January 1999 to June 2001. A retrospective chart review was performed to determine the incidence of fluid retention in this cohort. Physical signs of fluid retention were compared between TZD users and an age- and gender-matched control group of diabetic, non-TZD users with chronic HF who had fluid retention. Baseline clinical and echocardiographic data were compared between TZD users with and without fluid retention.

Results: Nineteen TZD users (17.1%) developed fluid retention, which reversed after drug withdrawal and presented predominantly as peripheral and not central edema. Comparing patients in the upper and lower tertiles of weight gain, more female patients and insulin users developed TZD-related fluid retention. However, there were no differences in the baseline New York Heart Association functional class or echocardiographic severity of cardiac dysfunction.

Conclusions: Although fluid retention after treatment with TZD in diabetic patients with chronic systolic HF occurs, the mechanism is undefined. Fluid retention related to TZD tends to be peripheral and is usually reversible after drug withdrawal. No direct association between the risk of fluid retention and the baseline degree of severity of HF was observed.

MeSH terms

  • Adult
  • Aged
  • Ascites / chemically induced
  • Diabetes Complications
  • Diabetes Mellitus / drug therapy*
  • Dilatation, Pathologic / chemically induced
  • Edema / chemically induced*
  • Female
  • Heart Failure / complications*
  • Heart Failure / physiopathology
  • Humans
  • Hypoglycemic Agents / administration & dosage
  • Hypoglycemic Agents / adverse effects*
  • Incidence
  • Jugular Veins / pathology
  • Male
  • Medical Records
  • Middle Aged
  • Predictive Value of Tests
  • Pulmonary Edema / chemically induced
  • Retrospective Studies
  • Severity of Illness Index
  • Systole
  • Thiazoles / administration & dosage
  • Thiazoles / adverse effects*
  • Thiazolidinediones*


  • Hypoglycemic Agents
  • Thiazoles
  • Thiazolidinediones
  • 2,4-thiazolidinedione