Thiazolidinediones and Risk of Heart Failure in Patients with or at High Risk of Type 2 Diabetes Mellitus

Abstract

In placebo-controlled trials of adult patients with or at high risk for type 2 DM, TZD therapy is significantly and consistently associated with a higher risk of HF. The risk of serious/severe HF is also increased with the use of TZDs. HF risks are similar to those of meta-analyses combining active- and placebo-controlled trials. The benefit/risk profile of TZDs should be considered when treating diabetic patients with or without prior HF.

Chemical Proteomics-Based Analysis of Off-Target Binding Profiles for Rosiglitazone and Pioglitazone: Clues for Assessing Potential for Cardiotoxicity

“…L-type calcium channels), and disruption of the cardiac sympathetic signaling. While rosiglitazone and pioglitazone off-target protein binding profiles are very similar in composition, there is the chance for variance in effects based on affinity for the particular protein leading to slight differences in efficacy or cytotoxicity 46, 48–50 . Additionally, it is recognized that long-term dosing of an animal model with rosiglitazone or pioglitazone may lead to increased levels of additional off-target binding partners and that indirect effects could contribute to efficacy and cardiotoxicity.…”

Standards of care for type 2 diabetes in China

“…Weight gain and oedema are common side effects of TZDs, and these side effects are more remarkable when TZDs are used in combination with insulin. TZD use has been correlated with increase risk of fractures and heart failure 57. Patients with heart failure (New York Heart Association heart function classification class II and above), active liver disease, transaminase elevations exceeding 2.5 times the upper limit of normal, and severe osteoporosis and fractures should not take TZDs.…”

The nature, significance, and glucagon‐like peptide‐1 analog treatment of brain insulin resistance in Alzheimer's disease

“…At those stages of AD, simply reducing peripheral insulin resistance is ineffective, as indicated by the failure of many T2D treatments to reduce AD risk or improve cognition in AD dementia, specifically treatments with peripherally administered insulin, metformin, sulfonylureas, and thiazolidinediones, such as rosiglitazone and pioglitazone [101,102]. The thiazolidinediones are also clinically compromised by their elevation of heart failure risk in those with prediabetes or T2D [103]. …”