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Metformin’s Impact on the Heart Differs in Men and Women

Study showed positive impact for women with type 2 diabetes but….

The researchers looked at three different outcomes to determine the impact of gender on response to diabetes therapies specifically as it relates to heart health. The stated goals were to determine if 1) sex affects the myocardial metabolic response to lipid lowering in T2DM, 2) altering lipid [fatty acid (FA) or triglyceride] delivery to the heart would lower the elevated myocardial lipid metabolism associated with T2DM, and 3) decreasing lipid delivery improves diastolic dysfunction in T2DM. The primary outcome studied was the change in myocardial fatty acid utilization.

The double-blind study included 78 participants (43 women, 35 men) who had T2DM who were randomized to either metformin, metformin plus rosiglitazone, or metformin plus Lovaza; each participant had tests including PET, echocardiograms, and whole body tracer studies at the initiation of the study and at 3 months. All 3 groups showed no significant impact on heart metabolism until gender was separated. In the metformin alone group, women experienced no significant change in whole body or myocardial FA clearance; however, men showed a decrease in whole body FA clearance therefore increasing myocardial FA utilization and oxidation (pre, 98 +/- 11; post, 115 +/- 12 nmol/g/min; P=0.02) resulting in a decrease of myocardial glucose uptake and utilization.

With individualization of treatments becoming more popular, further studies should assess gender-related differences in current diabetes therapy modalities. While this study did show clinically significant differences in the metformin alone group on myocardial metabolism, the study sample was quite small. Future research could assist with determining which therapies are best for men versus women in the treatment of diabetes.

Practice Pearls:

  • Metformin may have a different effect on men and women, and on fatty acid and glucose metabolism in the myocardium.
  • Increasing myocardial fatty acid metabolism will lead to reduced capacity of the heart to metabolize glucose which can result in heart damage and heart failure.
  • Individualization of therapy is important and patients’ lifestyles, adherence, potential underlying causes for T2DM and now gender may also play a role in choosing the right therapy.

Lyons, MR et al. Impact of sex on the heart’s metabolic and functional responses to diabetic therapies. Am J Physiol Heart Circ Physiol. 2013 Dec;305(11):H1584-91