Katrine L Kristensen1, Anton Pottegård2, Jesper Hallas2, Lars M Rasmussen3, Jes S Lindholt4. 1. Elitary Research Centre of Individualized Medicine in Arterial Disease (CIMA), Odense University Hospital, Odense, Denmark; Department of Vascular Surgery, Odense University Hospital, Odense, Denmark; Danish Diabetes Academy, Odense University Hospital, Odense, Denmark. Electronic address: katrine.lawaetz.kristensen@rsyd.dk. 2. Research Unit of Clinical Pharmacology and Pharmacy, Department of Public Health, University of Southern Denmark, Odense, Denmark. 3. Elitary Research Centre of Individualized Medicine in Arterial Disease (CIMA), Odense University Hospital, Odense, Denmark; Department of Clinical Biochemistry and Pharmacology, Odense University Hospital, Odense, Denmark. 4. Elitary Research Centre of Individualized Medicine in Arterial Disease (CIMA), Odense University Hospital, Odense, Denmark; Department of Vascular Surgery, Odense University Hospital, Odense, Denmark.
Abstract
OBJECTIVE: Diabetes counteracts formation and rupture of abdominal aortic aneurysms, possibly through arterial matrix accumulation. Use of metformin, on the other hand, reduces arterial accumulation of matrix molecules. Consequently, we hypothesized that metformin treatment may reverse the protective role of diabetes on the development and course of aneurysms, that is, that metformin would be associated with aneurysm rupture among individuals with diabetes. METHODS: Using nationwide Danish registry data, we performed a nested case-control study on the association between long-term use of metformin and ruptured abdominal aortic aneurysm (RAAA). The source population was defined as all individuals in Denmark with diabetes. Cases were all individuals within the source population who were hospitalized with a primary diagnosis of RAAA. For each case, 10 controls matched by age and sex were randomly selected from the source population by risk set sampling. The main exposure measure was a cumulative dispensing of 1000 g of metformin between January 1995 and the index date. RESULTS: We identified 362 cases of RAAA during 1998 to 2013, of which 83.7% occurred in men with a median age of 74 years. In total, 22.4% of the case population were long-term metformin users compared with 28.8% of the controls. We found a statistically nonsignificant protective effect of long-term metformin use toward RAAA with crude odds ratio (OR) of 0.74 (confidence interval, 0.54-1.00). When adjusted for covariates, OR increased to 0.84 (confidence interval, 0.61-1.17). None of the subgroups had ORs deviating substantially from the main result. CONCLUSIONS: Metformin use does not increase the risk of RAAA among individuals with diabetes.
OBJECTIVE:Diabetes counteracts formation and rupture of abdominal aortic aneurysms, possibly through arterial matrix accumulation. Use of metformin, on the other hand, reduces arterial accumulation of matrix molecules. Consequently, we hypothesized that metformin treatment may reverse the protective role of diabetes on the development and course of aneurysms, that is, that metformin would be associated with aneurysm rupture among individuals with diabetes. METHODS: Using nationwide Danish registry data, we performed a nested case-control study on the association between long-term use of metformin and ruptured abdominal aortic aneurysm (RAAA). The source population was defined as all individuals in Denmark with diabetes. Cases were all individuals within the source population who were hospitalized with a primary diagnosis of RAAA. For each case, 10 controls matched by age and sex were randomly selected from the source population by risk set sampling. The main exposure measure was a cumulative dispensing of 1000 g of metformin between January 1995 and the index date. RESULTS: We identified 362 cases of RAAA during 1998 to 2013, of which 83.7% occurred in men with a median age of 74 years. In total, 22.4% of the case population were long-term metformin users compared with 28.8% of the controls. We found a statistically nonsignificant protective effect of long-term metformin use toward RAAA with crude odds ratio (OR) of 0.74 (confidence interval, 0.54-1.00). When adjusted for covariates, OR increased to 0.84 (confidence interval, 0.61-1.17). None of the subgroups had ORs deviating substantially from the main result. CONCLUSIONS:Metformin use does not increase the risk of RAAA among individuals with diabetes.
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