Recent reports suggest that the negative association between diabetes mellitus and abdominal aortic aneurysm (AAA) may be driven by metformin, the world's most common antidiabetic drug, rather than diabetes per se. We sought to investigate the association between AAA growth rate, chemokine profile and metformin prescription in a contemporary Swedish cohort. Patients under surveillance for small AAA were identified at four Swedish vascular centers with active AAA screening programs. Annual AAA

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... owth rate, medical history and prescribed medications were recorded for linear regression analysis. In a subset of patients with AAA and controls without AAA or diabetes, plasma samples were available and analyzed for forty inflammatory chemokines. 526 patients were included for AAA growth analysis; 428 without type two diabetes mellitus (T2DM), 65 with T2DM and metformin prescription and 33 with T2DM but without metformin prescription. Patients were included form 2005 to 2017 with mean follow up of 3.2 (1.7) years and median annual AAA growth rate 1.6 mm, range -4.8 to 15.4 mm. Mean (SD) annual AAA growth rates were 2.3 (2.2) mm in non-T2DM patients versus 1.1 (1.1) mm in T2DM patients with metformin prescription and 1.6 (1.4) mm amongst those with T2DM without metformin prescription. With non-T2DM patients as reference in an unadjusted and two adjusted models, metformin prescription was significantly associated with reduced AAA growth rate (p<0.001, p=0.005 and p=0.024 respectively), but not T2DM without metformin prescription (p=0.137 p=0.331 and p=0.479 respectively). Amongst 240 patients with AAA (152 without T2DM, 51 with T2DM and metformin and 37 with T2DM without metformin) and 59 without AAA or T2DM, metformin prescription was associated with reduced expression of chemokines representing all classes of leukocytes. Metformin prescription is associated with reduced AAA growth rate, possibly mediated by broad anti-inflammatory effects. A randomized controlled trial is needed to determine what role metformin may play in AAA disease, particularly in absence of T2DM.