Glimepiride Use Among Patients with Chronic Type 2 Diabetes and Chronic Heart Failure

Long-term use of glimepiride, a third generation sulfonylurea, is associated with lower hospitalization rates for stroke or acute myocardial infarction, fewer emergency visits for heart failure, and decreased mortality for patients with type 2 diabetes (T2D) and chronic heart failure (CHF), according to a prospective cohort study published in the European Journal of Preventive Cardiology.

According to the authors of the study, “Patients with diabetes have poorer cardiovascular outcomes and prognosis and longer hospital stays than those without.” In treating patients with these comorbidities, providers often use glimepiride, which tends to be safe for treating cardiovascular disease.

However, the investigators indicated that there have been no randomized controlled trials to study glimepiride’s effects on the prognosis of T2D and confirmed CHF. In addition to measuring the effects of glimepiride on health outcomes associated with T2D and CHF, study researchers tested the hypothesis that glimepiride would molecularly dock soluble epoxide hydrolase. They also examined glimepiride’s effects on epoxyeicosatrienoic acid levels.

A total of 21,451 patients over the age of 18 with T2D and CHF were included in the study. Patients receiving glimepiride totaled 638 (60% men), while 20,813 (67.3% men) did not get treatment. Using a 1:1 propensity score matching analysis, the authors generated 509 pairs of glimepiride and non-glimepiride patients for follow-up. Statistical analysis involved Kaplan-Meier and Cox regression to compare the 2 groups for hospitalizations and emergency visits for heart failure, hospitalizations for acute myocardial infarction or stroke, cardiovascular mortality, and all-cause mortality.

After follow-up analyses—conducted via phone or on site questionnaires— researchers revealed that all-cause mortality with adjusted hazard ratio (HR) 0.47 (95% CI, 0.35-0.63; P <.001), cardiovascular mortality with HR 0.34 (95% CI, 0.24-0.48; P <.001), number of hospitalizations and emergency visits for heart failure, HR 0.42 (95% CI, 0.36-0.50; P <.001), and hospitalizations for acute myocardial infarction or stroke, HR 0.53 (95% CI, 0.38-0.73; P <.001), were significantly lower for patients in the glimepiride group than for those in the non-glimepiride group. Also, higher-dose glimepiride (2-4 mg/day) was associated with lower cardiovascular mortality than lower dose glimepiride (1 mg/day HR 0.55 [95% CI, 0.31-0.99; P =.047]). The authors also note that glimepiride was successful in epoxide hydrolase inhibition and raising epoxyeicosatrienoic acid levels.

The authors noted that one limitation of the study was that it did not employ a randomized clinical trial, given that not all treatments and indicators were well-matched for analysis. Also, all patients involved in the study were Chinese, limiting the findings’ generalizability to other populations. In addition, self-selection bias and call interference during follow-up calls could have reduced the similarity of information collection between the matched groups. Finally, the authors noted, “the cohort study could not determine the causal relationship between glimepiride treatment and endpoint events.”

The researchers concluded that long-term continuous use of glimepiride may reduce cardiovascular mortality and hospitalizations and emergency visits for heart failure in patients with T2D and CHF. The researchers also found that high-dose glimepiride (2-4 mg/day) reduced cardiovascular mortality and hospitalizations and emergency visits for heart failure at a higher rate than low-dose glimepiride.