Prediabetic men had significantly lower calcium score and load when treated with metformin. These benefits were not seen in women. An explanation could by the higher baseline cardiovascular risk in males vs. females. A group of 2,000 participants from DPP and DPPOS studies were followed for about 14 years. More research is needed before we call metformin a direct CVD reducing agent.
Background: Despite the reduced incidence of coronary heart disease (CHD) with intensive risk factor management, people with diabetes and prediabetes remain at increased CHD risk. Diabetes prevention interventions may be needed to reduce CHD risk. This approach was examined in the Diabetes Prevention Program (DPP) and its Outcome Study (DPPOS), a long-term intervention study in 3234 subjects with prediabetes (mean age 64) which showed reduced diabetes risk with lifestyle and metformin compared to placebo over 3.2 years.
Methods: The DPPOS offered periodic group lifestyle sessions to all participants and continued metformin in the originally randomized metformin group. Subclinical atherosclerosis was assessed in 2029 participants using coronary artery calcium (CAC) measurements after 14 years of average followup. The CAC scores were analyzed continuously as CAC severity, and categorically as CAC presence (CAC score>0), and reported separately in men and women.
Results: There were no CAC differences between lifestyle and placebo intervention groups, in either sex. CAC severity and presence were significantly lower among men in the metformin versus the placebo group (age-adjusted mean CAC severity: 39.5 vs 66.9; CAC presence: 75% vs 84%, p=0.02), but no metformin effect was seen in women. In multivariate analysis, the metformin effect in men was not influenced by demographic, anthropometric or metabolic factors, by the development of diabetes, or by use/non-use of statin therapy.
Conclusions: Metformin may protect against coronary atherosclerosis in prediabetes and early diabetes among men.