Raphael Wurm1, Michael Resl2, Stephanie Neuhold3, Rudolf Prager4, Helmut Brath5, Claudia Francesconi6, Greisa Vila7, Guido Strunk8, Martin Clodi9, Anton Luger7, Richard Pacher1, Martin Hülsmann1. 1. Department of Cardiology, Medical University of Vienna, Vienna, Austria. 2. Department of Endocrinology, Medical University of Vienna, Vienna, Austria Department of Internal Medicine, Barmherzige Brüder, Linz, Austria. 3. Division of Cardiothoracic and Vascular Anaesthesia and Intensive Care, Department of Anaesthesia, General Intensive Care and Pain Control, Medical University of Vienna, Vienna, Austria. 4. Karl Landsteiner Institute for Nephrology and Diabetes, Hietzing Hospital Vienna, Vienna, Austria. 5. Diabetes Outpatient Clinic, Health Center South, Vienna, Austria. 6. Diabetes Outpatient Clinic, Health Center Strohgasse, Vienna, Austria. 7. Department of Endocrinology, Medical University of Vienna, Vienna, Austria. 8. Complexity-Research, Research Institute for Complex Systems, Vienna, Austria. 9. Department of Internal Medicine, Barmherzige Brüder, Linz, Austria.
Abstract
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. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/
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. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/
Authors: Alexey V Zilov; Sulaf Ibrahim Abdelaziz; Afaf AlShammary; Ali Al Zahrani; Ashraf Amir; Samir Helmy Assaad Khalil; Kerstin Brand; Nabil Elkafrawy; Ahmed A K Hassoun; Adel Jahed; Nadim Jarrah; Sanaa Mrabeti; Imran Paruk Journal: Diabetes Metab Res Rev Date: 2019-07-24 Impact factor: 4.876