Metformin was associated with a decreased risk of cardiovascular events and death in diabetic patients with elevated NT-proBNP ≥300 pg/mL (HR 0.70, p=0.014).
Observational (n=2,024)
Do metformin and sulfonylureas reduce cardiovascular events and death in patients with diabetes mellitus with different cardiac risk profiles?
Metformin is associated with beneficial cardiovascular outcomes in patients with diabetes specifically when subclinical or clinical cardiovascular risk (indicated by elevated NT-proBNP) is present.
Effect estimate: HR 0.70
p-value: p=0.014
OBJECTIVES/BACKGROUND: Based on previous experiences, the Food and Drug Administration and the European Medicines Agency recommend that clinical trials for novel antidiabetic drugs are powered to detect increased cardiovascular risk. In this context, data concerning licensed drugs such as metformin and sulfonylureas are conflicting. The influence of baseline cardiovascular risk on any treatment effect appears obvious but has not been formally proven. We therefore evaluated association of metformin and sulfonylureas with cardiovascular events in patients with different cardiovascular risk profiles indicated by N-terminal of the prohormone brain natriuretic peptide (NT-proBNP) levels. METHODS: 2024 patients with diabetes mellitus were included in this observational study. The primary endpoint was defined as a combination of cardiovascular events and death. Association of metformin and sulfonylureas was assessed using Cox regression models. Possible differences of these associations in patients with different NT-proBNP levels were studied by stratifying and through interaction analysis. RESULTS: During a median follow-up of 60 months, the primary endpoint occurred in 522 (26%) of patients. The median age was 63 years. A Cox regression analysis was adjusted for site of treatment, concomitant medication, age, gender, body mass index, glycated haemoglobin, duration of diabetes, glomerular filtration rate, cholesterol, and history of smoking and cardiac disease. Metformin was associated with a decreased risk in the cohort with elevated NT-proBNP ≥300 pg/mL (HR 0.70, p=0.014) and a similar association was found for the interaction between metformin and NT-proBNP (p=0.001). There was neither an association for sulfonylureas nor a significant interaction between sulfonylureas and NT-proBNP. CONCLUSIONS: Metformin is associated with beneficial cardiovascular outcomes in patients with diabetes only when (sub)clinical cardiovascular risk defined by NT-proBNP levels is present.
Wurm et al. (Wed,) conducted a observational in diabetes mellitus (n=2,024). metformin and sulfonylureas was evaluated on combination of cardiovascular events and death (HR 0.70, p=0.014). Metformin was associated with a decreased risk of cardiovascular events and death in diabetic patients with elevated NT-proBNP ≥300 pg/mL (HR 0.70, p=0.014).