Glimepiride Stands Tall on Cardiovascular Safety Again: Latest Update

One of the most popular hypoglycaemic drugs for type 2 diabetes (T2D) patients is sulfonylurea (SU). The newer SU agents, including glimepiride, are thought to offer cardiac safety beyond their potent glucose-lowering effects. (3)

New research reaffirms the cardiovascular safety of long-term use of glimepiride among individuals with T2D and cardiovascular morbidities. (3)

Cardiovascular Safety and Outcomes with Glimepiride- Evidence from Cohort Study (3)

W. He et al. conducted a prospective cohort study to evaluate the effects of glimepiride on clinical outcomes among patients with T2D and chronic heart failure (CHF) and provide evidence for the clinical application of glimepiride in these patients.

The study enrolled 21451 adult inpatients with T2D and CHF. Patients were further divided into glimepiride and non-glimepiride groups. The study has been published in the European Journal of Preventive Cardiology.

Cardiovascular mortality, hospitalizations, and emergency visits for heart failure were the primary outcomes; all-cause mortality and hospitalizations for acute myocardial infarction or stroke were considered secondary outcomes. The clinical outcomes of the glimepiride treatment were analyzed using Propensity score matching (PSM).

• During hospitalization- 7 patients (0.9%) in the glimepiride group and 731 in the non-glimepiride group (3.5%) died (P=0.001).
• During follow-up, the all-cause mortality relatively reduced by 53% [adjusted hazard ratio (HR), 0.47; 95% confidence interval (CI), 0.35–0.63; P<0.001], cardiovascular mortality relatively reduced by 66% (adjusted HR, 0.34; 95% CI, 0.24–0.48; P><0.001), and a number of hospitalizations and emergency visits for heart failure relatively reduced by 58% (adjusted HR, 0.42; 95% CI, 0.36–0.50; P><0.001) and hospitalizations for acute myocardial infarction or stroke relatively reduced by 47% (adjusted HR, 0.53; 95% CI, 0.38–0.73; P>< 0.001) were significantly lower in the glimepiride group.
• Glimepiride treatment was more effective in reducing cardiovascular mortality, adjusted HR, 0.26; 95% CI, 0.16–0.41; P<0.001 in the in the >50 mm left ventricular diameter subgroup; adjusted HR, 0.23; 95% CI, 0.14–0.38; P<0.001 in the <8% HbA1c level subgroup.
• All-cause mortality (adjusted HR, 0.54; 95% CI, 0.34–0.87; P=0.010) and cardiovascular mortality (adjusted HR, 0.55; 95% CI, 0.31–0.99; P= 0.047) were significantly lower in the high-dose (2–4 mg/day) group than in the low-dose group.
• The cardiovascular mortality (log-rank p=0.009; adjusted HR, 0.51; 95% CI, 0.32–0.82; p=0.005), number of hospitalizations and emergency visits for heart failure (log-rank p<0.001; adjusted HR, 0.49; 95% CI, 0.39–0.62; p< 0.001), and number of hospitalizations for acute myocardial infarction or stroke (log-rank p=0.048; adjusted HR, 0.59; 95% CI, 0.38–0.93; p=0.024) were significantly lower in the low-dose (1 mg/day) group than in the non-glimepiride group.
• It was noteworthy that glimepiride exhibited good molecular docking with soluble epoxide hydrolase (sEH) and increased epoxyeicosatrienoic acid (EET), which inhibit inflammation, endothelial dysfunction, cardiac remodelling, and fibrosis, potentially responsible for its cardioprotective effects.

Kaplan–Meier survival curve for all-cause mortality between glimepiride group and non-glimepiride group. Adapted from W. He et.al, Glimepiride Use is Associated with Reduced Cardiovascular Mortality in Patients with Type 2 Diabetes and Chronic Heart Failure: A Prospective Cohort Study Eur J Prev Cardiol. 2022;zwac312

Kaplan–Meier survival curve for cardiovascular mortality between glimepiride group and non-glimepiride group. Adapted from W. He et.al, Glimepiride Use is Associated with Reduced Cardiovascular Mortality in Patients with Type 2 Diabetes and Chronic Heart Failure: A Prospective Cohort Study Eur J Prev Cardiol. 2022;zwac312

Clinical Care Points:

✔ The therapeutic options for people with T2DM have evolved due to the development of novel antihyperglycemic medications that can considerably lower mortality and morbidity from heart failure. Therefore, hypoglycaemic drug selection may impact the prognosis for CHF and other cardiovascular outcomes. (4)

✔ In patients with T2D and CHF, long-term continuous glimepiride treatment is linked with reduced mortality, fewer emergency room visits and hospitalizations for heart failure, and fewer hospitalizations for acute myocardial infarction or stroke. (3)

✔ Greater cardiovascular preventive benefits are associated with high-dose glimepiride compared to low-dose glimepiride. The cardiovascular protective effect of glimepiride may be related to an increase in EET levels through sEH inhibition. (3)

✔ The consistent reductions in cardiovascular mortality and CHF hospitalizations with glimepiride suggest that they could be considered in patients with T2DM with CHF.(3)

Reference:

1. Pop-Busui R, Januzzi JL, Bruemmer D, et al. Heart Failure: An Underappreciated Complication of Diabetes. A Consensus Report of the American Diabetes Association. Diabetes Care. 2022;45(7):1670-1690. doi:10.2337/dci22-0014

2. Shen J, Greenberg BH. Diabetes Management in Patients with Heart Failure. Diabetes Metab J. 2021;45(2):158-172.

3. He W, Yuan G, Han Y, et al. Glimepiride Use is Associated with Reduced Cardiovascular Mortality in Patients with Type 2 Diabetes and Chronic Heart Failure: A Prospective Cohort Study [published online ahead of print, 2022 Dec 27]. Eur J Prev Cardiol. 2022;zwac312. doi:10.1093/eurjpc/zwac312

4. Mazin I, Chernomordik F, Fefer P, Matetzky S, Beigel R. The Impact of Novel Anti-Diabetic Medications on CV Outcomes: A New Therapeutic Horizon for Diabetic and Non-Diabetic Cardiac Patients. Journal of Clinical Medicine. 2022; 11(7):1904