Metformin protects against coronary atherosclerosis in men with prediabetes
Long-term metformin treatment may confer a protective effect against atherosclerotic vascular disease in men, but not women, with prediabetes or early diabetes mellitus, according to a study.
Researchers analysed over 3.2 years of data on the efficacy of lifestyle and metformin vs placebo in 3,234 individuals with prediabetes (mean age 64 years). Among men (n=643), 215 were on metformin, 213 on lifestyle intervention and 215 on placebo. Among women (n=1,418), the respective numbers were 464, 468 and 486.
The coronary artery calcium (CAC) scores were evaluated continuously as CAC severity and categorically as CAC presence (CAC score >0) and reported separately in men and women. Subclinical atherosclerosis was then assessed in 2,029 participants with CAC measurements obtained over an average of 14 years of follow-up.
Lifestyle and placebo intervention groups in either sex did not significantly differ in terms of CAC scores. However, CAC severity and presence were significantly lower among men in the metformin vs the placebo group (age-adjusted mean CAC severity, 39.5 vs 66.9 Agatston units; p=0.04; CAC presence, 75 vs 84 percent; p=0.02). This beneficial effect of metformin was not seen in women.
Demographic, anthropometric or metabolic factors were not found to contribute to the metformin effect in men. Similarly, the effect was not influenced by the development of diabetes mellitus or by use/nonuse of statin therapy.
Coronary heart disease (CHD) is the single most important cause of morbidity and mortality in diabetes, with CHD risk increased by approximately twofold in type 2 diabetes patients. Interventions targeting factors that promote coronary atherosclerosis acceleration, such as dyslipidaemia, hypertension, hyperglycaemia and a procoagulant state, have contributed to the significantly reduced incidence of CHD in the general population in recent years. However, there remains a considerable diabetes-related excess CHD risk, highlighting the potential of lifestyle or pharmacologic interventions for diabetes prevention, implemented early in the progression from prediabetes to diabetes when clinical CHD events are less common. [N Engl J Med 2014;370:1514-1523; Lancet 2010;375:2215-2222; N Engl J Med 2010;362:1563-1574]
Findings of the present study contribute to the evidence base that metformin may protect against atherosclerotic vascular disease early in diabetes development and potentially extends the range of this action to include high-risk male prediabetic individuals, researchers said.
“Whether these findings translate into beneficial effects on CVD events will require ongoing follow-up,” they added.