Effect of Metformin and Lifestyle on Coronary Artery Calcium

Study Questions:

Is there an effect of lifestyle or metformin therapy on coronary artery calcium (CAC) score?


The investigators used the Diabetes Prevention Program (DPP) and its Outcome Study (DPPOS), a long-term intervention study in 3,234 subjects with prediabetes (mean [± standard deviation] age 64 ± 10 years), which showed reduced diabetes risk with lifestyle and metformin compared with placebo over 3.2 years. DPPOS offered periodic group lifestyle sessions to all participants and continued metformin in the originally randomized metformin group. Subclinical atherosclerosis was assessed in 2,029 participants using CAC measurements after 14 years of average follow-up. CAC was expressed both as a continuous variable (CAC severity) and as a categorical variable, mainly using a cut point of 0 (CAC presence), but also using cut points of 10 and 100 Agatston units (AU).


Mean age of participants at the time of scanning was 67 ± 10 years in men and 63 ± 9 years in women, with mean study duration of 13.7 ± 0.08 years since randomization. During DPPOS, 70% of nondiabetic metformin participants took metformin in any amount (mean 9.6 years) compared with 1% of nondiabetic participants in the lifestyle and 3% in the placebo groups (1.7 years in both groups). Statin use increased significantly over time in DPPOS to >50% of participants and not different across treatment groups. After 14 years of follow-up, 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 AU, p = 0.04; CAC presence: 75% vs. 84%, p = 0.02), but no metformin effect was seen in women. CAC severity was higher among statin users for both men and 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/nonuse of statin therapy.


The authors concluded that metformin may protect against coronary atherosclerosis in prediabetes and early diabetes among men.


The initial DPP lifestyle intervention reduced incidence of diabetes by 58% and metformin by 31% compared with placebo during an average follow-up of 3.2 years. The findings suggest metformin either reduces development of atherosclerosis or reduces calcification of plaque compared with lifestyle. The lack of an effect in women is unclear. But the baseline age in women was 49 years and about 30% were between ages 25-44 years, which would reduce baseline coronary atherosclerosis and be associated with the negative effect of estrogens on coronary calcification.

Clinical Topics: Diabetes and Cardiometabolic Disease, Dyslipidemia, Prevention, Atherosclerotic Disease (CAD/PAD), Nonstatins, Novel Agents, Statins

Keywords: Atherosclerosis, Coronary Artery Disease, Diabetes Mellitus, Hydroxymethylglutaryl-CoA Reductase Inhibitors, Life Style, Metabolic Syndrome X, Metformin, Outcome Assessment (Health Care), Plaque, Atherosclerotic, Primary Prevention, Prediabetic State

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