Metformin may protect against coronary atherosclerosis in men with prediabetes
Effect of Long-Term Metformin and Lifestyle in the Diabetes Prevention Program and its Outcome Study on Coronary Artery Calcium
Literature - Goldberg RB, Aroda VR, Bluemke DA, et al, on behalf of the Diabetes Prevention Program Research Group - Circulation 2017; published online ahead of printBackground
The Diabetes Prevention Program (DPP) and its Outcome Study (DPPOS) are evaluating the effects of therapeutic interventions on long-term health outcomes in subjects with prediabetes. So far it was shown that intensive lifestyle change or metformin treatment reduce the incidence of diabetes and the CVD risk in subjects at high risk for diabetes [1-3].
Coronary artery calcium (CAC) is an early marker of subclinical coronary atherosclerosis and predicts CHD events in individuals at high CHD risk, with or without diabetes [4,5].
In this analysis, the DPP/DPPOS treatment effects on CAC measurements were assessed, using CAC severity, derived from the logarithmically transformed CAC score ([log(CAC+1)]) as the primary measure, and the presence of CAC (CAC>0) as the secondary measure.
Main results
- CAC severity was significantly higher in men compared with women (p<0.001).
- In men, CAC severity was significantly lower in the metformin group compared with the lifestyle group in unadjusted analyses, and after age-adjustment, it was 41% lower in the metformin group compared with placebo.
- No effect of metformin to lower CAC severity was seen in women.
- Among men, but not in women, the presence of CAC>0 was significantly lower in the metformin group compared with the other two groups (10.7% lower versus placebo and 11.7% lower versus lifestyle), but this was not the case for the CAC>10 or CAC>100 categories.
- By age groups, both CAC severity and CAC>0 were significantly lower in the 25-44 year age group among men in the metformin versus placebo groups, with a similar tendency in the older age groups.
- CAC severity was significantly higher in the lifestyle group compared with the placebo group among women in the 25-44 year age group.
- CAC severity and presence among men in the metformin group tended to be lower in both those with and without diabetes and in all race/ethnic subgroups although this did not reach significance (except for CAC>0 in those without diabetes).
- Among women, there was an interaction between diabetes status and treatment group for CAC severity (p=0.04).
- CAC severity was higher among statin users for both men and women.
Conclusion
In the Diabetes Prevention Program and its Outcome Study, men, but not women with prediabetes treated with metformin for an average duration of 14 years had lower coronary calcium scores compared with the placebo group. No difference in coronary calcium scores was observed in the group receiving a lifestyle intervention as compared to the placebo group. These findings provide evidence that metformin may protect against coronary atherosclerosis in men with prediabetes.
References
1. Knowler WC, Barrett-Connor E, Fowler SE, et al. Reduction in the incidence of type 2 diabetes with lifestyle intervention or metformin. N Engl J Med. 2002;346:393-403.
2. The Diabetes Prevention Program Research Group, Goldberg RB, Temprosa M, Haffner S, et al. The Effect of Progression from Impaired Glucose Tolerance to Diabetes on Cardiovascular Risk Factors and its Amelioration by Lifestyle and Metformin Intervention: The Diabetes Prevention Program Randomized Trial. Diabetes Care. 2009;32:726-732.
3. Goldberg RB, Temprosa MG, Mather KJ, et al; for the Diabetes Prevention Program Research Group*. Lifestyle and Metformin Interventions Have a Durable Effect to Lower CRP and tPA Levels in the Diabetes Prevention Program Except in Those Who Develop Diabetes. Diabetes Care. 2014;37:2253-2260.
4. Detrano R, Guerci AD, Carr JJ, et al. Coronary calcium as a predictor of coronary events in four racial or ethnic groups. N Engl J Med. 2008;358:1336-1345.
5. Khaleeli E., Peters S.R., Bobrowsky K., et al.: Diabetes and the associated incidence of subclinical atherosclerosis and coronary artery disease: implications for management. Am Heart J. 2001;141:637-644.
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