Abstract
Skeletal muscle blood flow is attenuated in older adults performing dynamic exercise which is due, in part, to impaired local vasodilatory mechanisms. Recent preclinical and clinical studies have shown that sodium-glucose cotransporter 2 (SGLT2) inhibitors improve vasodilator function at rest. However, the extent to which this improvement extends to exercise is unknown. PURPOSE: To test the hypothesis that compared with placebo, short-term administration of an SGLT2 inhibitor will increase skeletal muscle blood flow in older adults performing unilateral plantar flexion exercise via increased vascular conductance. METHODS: We utilized a randomized, single-blind, placebo-controlled crossover design. Four older adults (3 women; age 63 ± 7 yrs; height 168 ± 6 cm; weight 77 ± 12 kg) were studied after completing a 7-day regimen of empagliflozin (10 mg/day) or placebo. A 30-day washout period separated the two testing phases. During experimentation, participants performed graded (3, 6, and 9 kg) unilateral plantar flexion exercise with a duty cycle of 1-s contraction and 2-s relaxation (20 contractions/min). Beat-by-beat blood pressure (Finometer) and leg blood flow (duplex ultrasonography of the superficial femoral artery) were recorded in the last minute of each 4-minute stage of exercise. A 1-min rest period separated each exercise stage. Vascular conductance, an index of vasodilation, was calculated as leg blood flow divided by mean arterial blood pressure. The exercise pressor response was calculated as the difference in mean arterial blood pressure measured during each exercise stage and baseline. RESULTS: Leg blood flow, vascular conductance, and mean arterial blood pressure did not differ at rest between placebo and SGLT2 inhibition (all P > 0.3). Compared with placebo (3 kg: Δ 180 ± 111 ml/min, 6 kg: Δ 257 ± 76 ml/min, and 9 kg: Δ 327 ± 55 ml/min), the change in leg blood flow during exercise tended to increase with SGLT2 inhibition (3 kg: Δ 204 ± 67 ml/min, 6 kg: Δ 273 ± 48 ml/min, and 9 kg: Δ 350 ± 60 ml/min; P = 0.1). The increase in vascular conductance during exercise was greater with SGLT2 inhibition (3 kg: Δ 1.8 ± 0.4 ml/min/mmHg, 6 kg: Δ 2.5 ± 0.4 ml/min/mmHg, and 9 kg: Δ 3.2 ± 0.3 ml/min/mmHg) when compared with placebo (3 kg: Δ 1.3 ± 0.6 ml/min/mmHg, 6 kg: Δ 1.9 ± 0.5 ml/min/mmHg, and 9 kg: Δ 2.4 ± 0.5 ml/min/mmHg; P < 0.01). Interestingly, SGLT2 inhibition also attenuated the pressor response across all stages of exercise (placebo: 3 kg, Δ 18 ± 14 mmHg; 6 kg, Δ 23 ± 16 mmHg; 9 kg, Δ 26 ± 17 mmHg vs. SGLT2 inhibition: 3 kg, Δ 11 ± 4 mmHg; 6 kg, Δ 11 ± 2 mmHg; 9 kg, Δ 13 ± 4 mmHg; P < 0.01). CONCLUSIONS: Our preliminary data suggest that SGLT2 inhibition improves peripheral and central hemodynamic responses to exercise in older adults. These findings highlight the potential of SGLT2 inhibitors to enhance functional capacity in this population, which could reduce long-term cardiovascular morbidity and mortality. However, additional data are needed to confirm these initial findings.
Recommended Citation
Peyrovi, Harrison A.; Romero, Steven A.; Tune, Johnathan D.; Ruiz-Pick, Ysabella; Kichloo, Asim; Dick, Gregory M.; and Gilliland, Brenda L.
(2025)
"Effect of Sodium Glucose Cotransporter 2 Inhibition on Exercise Hyperemia in Older Adults,"
International Journal of Exercise Science: Conference Proceedings: Vol. 2:
Iss.
17, Article 56.
Available at:
https://digitalcommons.wku.edu/ijesab/vol2/iss17/56
Included in
Health and Physical Education Commons, Medical Education Commons, Sports Sciences Commons
