CHD is the single most important cause of mortality and morbidity in diabetes mellitus. Despite intense management of CHD-targeted risk factors there is still much excess CHD risk in T2DM. The argument is that earlier preventative therapy could be of benefit in reducing the risk of CHD in T2DM.
The Diabetes Prevention Program (DPP) and the Diabetes Prevention Program Outcome Study (DPPOS) is testing the effect of intense lifestyle change and metformin treatment to evaluate the effect on cardiovascular risk profile in diabetic patients.
This study demonstrated a reduction of the development of diabetes mellitus and it showed an improvement in the risk profile of cardiovascular risk factors. The risk of developing diabetes was reduced by 58% with life-style and 31% by metformin.
Unfortunately, there are too few CVD outcome events to assess the effect of these interventions on CVD outcomes. Coronary artery calcium (CAC) measurements reflect total coronary atherosclerotic burden and can be used as an effective non-invasive tool to predict CHD events in cohorts with and without T2DM.
The aim of this part of the DPP study was to assess the effect of treatment of pre-diabetic patients with metformin on the CAC as an early marker of coronary atherosclerosis.
This study included 3234 people with pre-diabetes with a mean age of 64 years and were evaluated for the effect of placebo or metformin and life-style change over 3.2 years for this particular study.
Subclinical atherosclerosis was assessed in 2029 people with coronary artery calcium score measurements at year 10 of follow-up of the original study participants.
There were no differences in the CAC score in the group with lifestyle intervention and in the placebo group in both sexes.
In men, the group who received metformin had a significant reduction in the CAC score and also a significant reduction in the presence of CAC. Multivariate analysis in men showed no influence of anthropometric or metabolic factors or by the use or non-use of statins. In women, there were no effect of metformin in the CAC score.
Metformin previously demonstrated a significant reduction in the development of T2DM in pre-diabetic patients but it was only about half as effective as lifestyle management.
At least 10 years of metformin use in men showed significant reduction in coronary artery calcium scores but lifestyle changes alone did not show this in contrast to its effect on reducing the risk of developing diabetes.
Why women did not benefit is not known, but it could be that women have less coronary atherosclerosis and calcium scores than men and therefore an effect of metformin may be more difficult to show.
This is the first evidence that metformin may protect against coronary atherosclerosis.
Author: Prof James Ker