Since the first sulfonylurea (SU; tolbutamide) was commercially launched in Germany in 1956, SUs, as the oldest oral hypoglycemic drugs, have been developed for three generations and are commonly used for patients with T2D. In 2008, the US Food and Drug Administration and European Drug Administration required cardiovascular safety certification for all hypoglycemic drugs, resulting in increased related clinical trials. Currently, data on the relationship between SUs and cardiovascular outcomes are limited, and the cardiovascular effects remain controversial in observational studies. Third-generation SUs, such as glimepiride, are widely used for treating T2D because of their definite hypoglycemic efficacy, relatively low risk of hypoglycemia, convenient daily use, and low price. Glimepiride has good cardiovascular safety according to randomized controlled trials (RCTs). The proportion of SUs used in patients with heart failure is as high as 60.4%. Although some studies have shown that SUs are neutral in terms of hospitalization rates and adverse cardiovascular events in patients with CHF, no standard RCT of glimepiride has been conducted to study its effect on the prognosis of patients with T2D and confirmed CHF. Glimepiride inhibits soluble epoxide hydrolase (sEH), thus reducing epoxyeicosatrienoic acid (EET) degradation . Increased EET production exerts protective effects on the heart, indicating the potential cardiovascular effect of glimepiride.~This retrospective cohort study aimed to evaluate the effects of glimepiride on the clinical outcomes of patients with T2D and CHF and provide theoretical evidence for the clinical application of glimepiride in these patients.
Thirty years ago, Dzau and Braunwald introduced the concept of a continuum of cardiovascular diseases and defined them as a series of events caused by numerous related and unrelated risk factors, thus developing to end-stage heart disease through many pathophysiological pathways and processes. Owing to treatment concept changes and the urgency of investigating T2D combined with CHF, SUs are being re-evaluated, of which glimepiride is undoubtedly the most promising.