Does Metformin inhibit growth of small abdominal aortic aneurysms? A randomised controlled trial(MetAAA)

Title [sv]

Minskar Metformin tillväxten av små bukaortaaneurysm? En randomiserad kontrollerad studie(MetAAA)

Title [en]

Abstract [sv]

Bakgrund: Worldwide ~20 million people have an abdominal aortic aneurysm (AAA) and the main complication of AAA, aortic rupture, leads to about 200,000 deaths each year. To prevent rupture, early detection by screening risk groups and surgical repair when appropriate is recommended. A general AAA screening program, targeting 65-year-old men, has gradually been introduced in Sweden since 2006, reaching nationwide coverage in 2015. Most AAAs detected are small and treatment could be instigated to avoid later requirement for surgery or rupture. Currently however there is no drug therapy for AAA. Experimental and observational studies suggest that the drug metformin, the most widely used antidiabetic drug for type II diabetes in the world, inhibits AAA growth by inhibiting key pathological mechanisms, including inflammation and extracellular matrix (ECM) remodeling.Målsättning: The purpose of this multi-center randomized controlled trial is to examine if metformin slows AAA growth. The primary aim is to examine if 1.5g metformin administered daily for a two year period slows AAA growth in patients with small AAAs who do not have diabetes measured as computed tomography (CT) imaging assessed AAA diameter (80% power to detect <20% difference). The secondary aims are to examine if metformin (vs placebo); a) limits increase in CT-assessed AAA volume; b) ultrasound assessed AAA diameter; c) favorably modify circulating inflammation and matrix remodeling biomarkers; d) improve health-related QoL; and e) represent a cost-effective treatment to limit AAA surgery. Long-term follow-up will be studied in a post-randomization phase cohort study.Arbetsplan: 300 men with small AAAs from four sites with established screening programs and research infrastructure (Uppsala, Malmö, Falun, Gävle) will be randomized to treatment with metformin or placebo for two years. CT and ultrasound imaging, blood sampling and QoL assessment will be performed at baseline and after two years. The Swedish nationwide AAA screening program together with a study organization with the required expertise and experience gives us a unique opportunity to perform this trial.Betydelse: Access to a growth-inhibiting treatment of small AAA would be of great importance, with fewer who need to undergo major surgery and/or rupture of their AAA. It has great potential for the individual patient as well as for society, with saved lives, reduced suffering with better quality of life and cost-saving.

Abstract [en]

Bakgrund: Worldwide ~20 million people have an abdominal aortic aneurysm (AAA) and the main complication of AAA, aortic rupture, leads to about 200,000 deaths each year. To prevent rupture, early detection by screening risk groups and surgical repair when appropriate is recommended. A general AAA screening program, targeting 65-year-old men, has gradually been introduced in Sweden since 2006, reaching nationwide coverage in 2015. Most AAAs detected are small and treatment could be instigated to avoid later requirement for surgery or rupture. Currently however there is no drug therapy for AAA. Experimental and observational studies suggest that the drug metformin, the most widely used antidiabetic drug for type II diabetes in the world, inhibits AAA growth by inhibiting key pathological mechanisms, including inflammation and extracellular matrix (ECM) remodeling.Målsättning: The purpose of this multi-center randomized controlled trial is to examine if metformin slows AAA growth. The primary aim is to examine if 1.5g metformin administered daily for a two year period slows AAA growth in patients with small AAAs who do not have diabetes measured as computed tomography (CT) imaging assessed AAA diameter (80% power to detect <20% difference). The secondary aims are to examine if metformin (vs placebo); a) limits increase in CT-assessed AAA volume; b) ultrasound assessed AAA diameter; c) favorably modify circulating inflammation and matrix remodeling biomarkers; d) improve health-related QoL; and e) represent a cost-effective treatment to limit AAA surgery. Long-term follow-up will be studied in a post-randomization phase cohort study.Arbetsplan: 300 men with small AAAs from four sites with established screening programs and research infrastructure (Uppsala, Malmö, Falun, Gävle) will be randomized to treatment with metformin or placebo for two years. CT and ultrasound imaging, blood sampling and QoL assessment will be performed at baseline and after two years. The Swedish nationwide AAA screening program together with a study organization with the required expertise and experience gives us a unique opportunity to perform this trial.Betydelse: Access to a growth-inhibiting treatment of small AAA would be of great importance, with fewer who need to undergo major surgery and/or rupture of their AAA. It has great potential for the individual patient as well as for society, with saved lives, reduced suffering with better quality of life and cost-saving.

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