Metformin Alters Exercise Training Induced Blood Pressure and Aortic Waveform Adaptations in Adults at Risk for Metabolic Syndrome

ABSTRACT Metformin reduces hyperglycemia and cardiovascular disease risk. However, no study has determined if metformin alters blood pressure and/or aortic waveforms in an exercise intensity dependent manner. We tested if metformin alters blood pressure and aortic waveforms before and during insulin‐stimulation following low and high intensity exercise training. In a double‐blind, placebo controlled trial, participants were randomized to low intensity exercise plus placebo (∼55% VO 2 max 5 days/week, LoEx+PL, n = 22) or metformin (2000 mg/day, LoEx+Met, n = 21) and high intensity exercise plus placebo (∼85% VO 2 max 5 days/week, HiEx+PL, n = 24) or metformin (HiEx+Met, n = 24) for 16 weeks. Carotid‐femoral pulse wave velocity (cfPWV) was assessed to determine arterial stiffness. A 120 min euglycemic‐hyperinsulinemic clamp (40mU/m 2 /min, 90 mg/dL) was conducted to assess peripheral and central blood pressures as well as aortic waveforms via applanation tonometry. Inflammatory measures (e.g., hs‐CRP, IL‐8, MMP‐1 and MMP‐7) along with fitness (VO 2 max) and body composition (DXA) were also analyzed. While LoEx+PL tended to decrease cfPWV ( p = 0.051), HiEx+Met reduced fasting peripheral diastolic blood pressure (pDBP; p < 0.05) and all treatments except HiEx+Met increased fasting central pulse pressure ( p < 0.05). Upon insulin‐stimulation, pDBP and reflection magnitude increased while pulse pressure amplification (PPA) decreased after LoEx+Met and HiEx+Met compared with LoEx+PL and HiEx+PL independent of exercise intensity (all, p < 0.05). Interestingly, fasting MMP‐1 ( p < 0.05) and MMP‐7 ( p = 0.063) tended to be higher after Met compared with PL, independent of exercise intensity. In conclusion, metformin altered blood pressure and aortic waveform adaptations in relation to inflammation following exercise training in adults at risk for metabolic syndrome. Trial Registration : NCT03355469