Can metformin treatment reverse the protective role of diabetes on the development and course of aneurysms?

Can metformin treatment reverse the protective role of  diabetes on the development and course of aneurysms? -
12.06.17

A new article, published in Journal of Vascular Surgery (May 2017) by Danish Diabetes Academy PhD student Katrine Lawaetz Kristensen, shows that metformin use is not associated with aneurysm rupture among individuals with diabetes. 

DIABETES AS A PROTECTIVE FACTOR AGAINST RAAA

According to Kartine L. Kristensen, 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", states Katrine.

STUDY DESIGN USING DANISH REGISTRY DATA

Using nationwide Danish registry data, they 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.

METFORMIN DOES NOT INCREASE THE RISK OF RAAA IN DIABETICS

"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 was 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", Katrine L. Christensen argues.

Accordingly she concludes that "metformin use does not increase the risk of RAAA among individuals with diabetes".

AUTHORS AND AFFILIATIONS

Kristensen KL1, 2, Pottegaard A3, Hallas J3, RasmussenLM4, Lindholt JS1

1Elitary Research Centre of Individualized Medicine in Arterial Disease (CIMA), Odense University Hospital, Odense, Denmark; Department of Vascular Surgery, Odense University Hospital, Odense, Denmark
2
Danish Diabetes Academy, Odense, Denmark
3Research Unit of Clinical Pharmacology and Pharmacy, Department of Public Health, University of Southern Denmark, Odense, Denmark
4Elitary 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

Source: Journal of Vascular Surgery