From the Guidelines
Thiazolidinediones (TZDs) should be avoided in patients with heart failure due to their strong and consistent relationship with increased risk of heart failure, as demonstrated by recent studies 1. The use of TZDs, such as pioglitazone and rosiglitazone, can lead to fluid retention and edema, which can worsen heart failure symptoms or precipitate heart failure exacerbations. This is because TZDs activate peroxisome proliferator-activated receptor gamma (PPAR-γ), which improves insulin sensitivity but also promotes sodium reabsorption in the distal nephron of the kidney, resulting in increased plasma volume, peripheral edema, and weight gain in many patients. Some key points to consider when managing patients with heart failure and diabetes include:
- The risk of heart failure hospitalizations associated with TZD use is significant, with some studies suggesting an increase of 30-40% 1.
- Alternative diabetes medications, such as metformin, GLP-1 receptor agonists, or SGLT2 inhibitors, should be considered instead for patients with heart failure, as they may have cardiovascular benefits and do not increase the risk of heart failure hospitalizations 1.
- The American Heart Association and other organizations recommend avoiding or discontinuing TZDs in patients with heart failure, and considering alternative treatment options 1.
- Recent studies have consistently shown that SGLT2 inhibitors can reduce the risk of heart failure hospitalizations, making them a valuable treatment option for patients with heart failure and diabetes 1.
From the FDA Drug Label
Thiazolidinediones, including ACTOS, cause or exacerbate congestive heart failure in some patients ACTOS is not recommended in patients with symptomatic heart failure. Initiation of ACTOS in patients with established NYHA Class III or IV heart failure is contraindicated Fluid retention may lead to or exacerbate heart failure. Patients with NYHA Class III and IV cardiac status were not studied during pre-approval clinical trials and ACTOS is not recommended in these patients
Avoiding TZD's in heart failure is recommended because they can cause or exacerbate congestive heart failure in some patients. This is due to fluid retention, which can lead to or worsen heart failure.
- Key points:
From the Research
Reasons to Avoid TZDs in Heart Failure
- Thiazolidinediones (TZDs) can cause fluid retention, which may increase the risk of heart failure, a common complication of type 2 diabetes mellitus 3.
- Patients with heart failure symptoms, particularly New York Heart Association Class III or IV, should not use TZDs due to the risk of fluid retention 4.
- The use of TZDs is associated with several adverse effects, including edema, weight gain, and heart failure 5.
- Although some studies suggest that TZDs can be used cautiously in patients with mild heart failure, careful monitoring of volume status is necessary 6.
Precautions and Considerations
- Special precaution is warranted in patients with congestive heart failure or hepatic disease when using TZDs 7.
- Monitoring of liver enzymes is recommended for the first year of therapy with TZDs 7.
- The safety profile of TZDs should be considered, including the risk of heart failure, when deciding to use these medications in clinical practice 5.
Patient Characteristics
- Patients on TZDs tend to be older (mean age, 69.2±10.7 years) and have a high prevalence of coronary disease (61.9%) and class 3 obesity (17.2%) 3.
- At least a quarter, and up to two-fifths, of patients currently treated with TZDs have some evidence of heart failure and therefore should not be candidates for this therapy 3.