Thiazolidinedione may reduce CV events and adverse renal events in diabetic patients: Study

A new study published in the Journal of Clinical Endocrinology and Metabolism showed that among type 2 diabetes mellitus (T2DM) patients with AKD, thiazolidinedione (TZD) showed a significant decrease in mortality, cardiovascular events, and adverse renal events. Over 422 million people suffer from diabetes (WHO 2023) throughout the globe, and by 2045, this prevalence may rise to 700 million. About 90% of people with diabetes are diagnosed with T2DM, which is caused by insulin insufficiency brought on by tissue insulin resistance and pancreatic β-cell malfunction.

Reduced estimated glomerular filtration rate (eGFR) < 60 mL/min/1.73 m² and/or structural kidney or urine abnormalities are characteristics of chronic kidney disease (CKD). By stimulating the peroxisome proliferator-activated receptor gamma (PPARγ) which is a nuclear transcription factor that controls many metabolic pathways, thiazolidinediones (glitazones), improve insulin sensitivity.

The function of thiazolidinedione in these individuals during the acute kidney disease (AKD) phase has not been well studied. In order to determine if utilizing TZD during AKD may lower the chance of significant negative effects in the future, Li-Yang Chang and colleagues carried out this investigation.

Prior to September 30, 2022, this research used the TriNetX platform to administer TZD to patients with type 2 diabetes mellitus (T2DM) within 90 days of receiving an AKD diagnosis. The risk of major adverse cardiovascular events (MACE), major adverse renal events (MAKE), and all-cause mortality are examples of clinical endpoints. Using 1:1 ratio propensity score matching (PSM), hazard ratios (HRs) and 95% CIs were computed.

TZD users were substantially less likely than those in the control group to experience an acute myocardial infarction, an intracerebral infarction, a major adverse cardiovascular event, or a major adverse renal event. However, there was no discernible decrease the combined risk of heart failure and death in TZD users.

According to subgroup studies, the advantages of using TZD were unaffected by hypertension, and while combining TZD with insulin, angiotensin-converting enzyme inhibitors, or angiotensin receptor blockers enhanced results, doing so with metformin had neutral effects.

Despite similar results for severe adverse cardiovascular and renal events, long-term TZD users had a higher mortality risk decrease than new users. The benefits of TZD usage continued long after stopping, according to landmark research. Overall, these results point to a possible advantage of using TZD to treat cardiovascular events in T2DM patients who also have AKD.

Reference:

Chang, L.-Y., Liao, H.-W., Chen, J.-Y., & Wu, V.-C. (2024). Enhanced Outcomes in Type 2 Diabetes Patients With Acute Kidney Disease Through Thiazolidinedione. In The Journal of Clinical Endocrinology & Metabolism. The Endocrine Society. https://doi.org/10.1210/clinem/dgae796