Long-term glimepiride use may improve survival in patients with diabetes, chronic HF
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Long-term use of glimepiride may improve survival and reduce hospitalizations in hospitalized patients with concomitant type 2 diabetes and chronic HF, researchers reported.
In addition, high-dose daily glimepiride further reduced risk for CV mortality in this patient population compared with low-dose treatment, according to a prospective study published in the European Journal of Preventive Cardiology.
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“Third-generation [sulfonylureas], such as glimepiride, are widely used for treating [type 2 diabetes] 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,” Wu He, MD, of the division of cardiology at Tongji Hospital, Tongji Medical College, and the Hubei Key Laboratory of Genetics and Molecular Mechanisms of Cardiological Disorders, and colleagues wrote. “The proportion of [sulfonylureas] used in patients with heart failure is as high as 60.4%. Some studies have shown that [sulfonylureas] are neutral in terms of hospitalization rates and adverse cardiovascular events in patients with [sulfonylureas], no standard [randomized clinical trial] of glimepiride has been conducted to study its effect on the prognosis of patients with [type 2 diabetes] and confirmed [chronic HF].”
For the prospective clinical trial, researchers evaluated the clinical outcomes of glimepiride use compared with nonuse in a propensity-matched cohort consisting of 509 patients who used glimepiride and 509 who did not (mean age, 67 years; 67% men). The glimepiride group was divided into high-dose (2-4 mg per day) and low-dose (1 mg per day) arms. Median follow-up was 34.1 months.
Chronic HF was defined as left ventricular ejection fraction less than 50%, N-terminal pro- B-type natriuretic peptide level more than 125 pg/mL and/or LV diameter of 50 mm or more.
The primary outcomes were CV mortality and hospitalizations and emergency visits for HF. Secondary outcomes included were all-cause mortality and hospitalizations for acute MI or stroke.
Long-term glimepiride for diabetes and chronic HF
During follow-up, long-term daily glimepiride was associated with lower risk for all-cause mortality (adjusted HR = 0.47; 95% CI, 0.35-0.63; P < .001), CV mortality (aHR = 0.34; 95% CI, 0.24-0.48; P < .001), hospitalizations and emergency visits for HF (aHR = 0.42; 95% CI, 0.36-0.5; P < .001) and hospitalizations for acute MI or stroke (aHR = 0.53; 95% CI, 0.38-0.73; P < .001) compared with non-use in patients with diabetes and chronic HF.
In addition, high-dose glimepiride was associated with a greater reduction in CV mortality compared with low-dose glimepiride (aHR = 0.55; 95% CI, 0.31-0.99; P = .047).
Glimepiride inhibits soluble epoxide hydrolase
Researchers also conducted analyses to predict the molecular docking of glimepiride with soluble epoxide hydrolase and evaluated the effects of glimepiride on levels of epoxyeicosatrienoic acid.
He and colleagues observed good molecular docking of glimepiride with soluble epoxide hydrolase, with binding energies of –8.51 kcal per mol, according to the study.
Glimepiride also increased levels of epoxyeicosatrienoic acid, decreased levels of dihydroxyeicosatrieonic acids and increased the epoxyeicosatrienoic/dihydroxyeicosatrieonic acids ratio, suggesting that glimepiride may inhibit soluble epoxide hydrolase.
“Our results suggest that glimepiride can reduce all-cause mortality, cardiovascular mortality, hospitalizations and emergency visits for heart failure, and hospitalizations for acute myocardial infarction or stroke in patients with [type 2 diabetes] and [chronic HF] and has similar effects in different subgroups of concern,” the researchers wrote. “Owing to treatment concept changes and the urgency of investigating [type 2 diabetes] combined with [chronic HF], [sulfonylureas] are being reevaluated, of which glimepiride is undoubtedly the most promising.”
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