Key result
Sildenafil administration did not improve exercise capacity (V̇o2peak 31.8 vs 32.1 ml·min−1·kg−1; P=0.42) compared with placebo in subjects with diabetes mellitus.
Why the study?
Exercise capacity is frequently reduced in people with DM, but the contribution of pulmonary microvascular dysfunction remains undefined.
Does sildenafil improve exercise capacity in people with diabetes mellitus?
RCT (n=60)
Double-blind
Crossover
Does sildenafil improve exercise capacity in people with diabetes mellitus?
Absolute Event Rate: 31.8% vs 32.1%
p-value: p=0.42
Sildenafil administration causes modest acute improvements in central hemodynamics but does not improve exercise capacity in people with diabetes mellitus.
Sildenafil should not be prescribed to improve exercise capacity in diabetes; challenges translation of acute hemodynamic benefits to functional gains.
Exercise capacity is frequently reduced in people with diabetes mellitus (DM), and the contribution of pulmonary microvascular dysfunction remains undefined. We hypothesized that pulmonary microvascular disease, measured by a novel exercise echocardiography technique termed pulmonary transit of agitated contrast (PTAC), would be greater in subjects with DM and that the use of pulmonary vasodilator agent sildenafil would improve exercise performance by reducing right ventricular afterload. Forty subjects with DM and 20 matched controls performed cardiopulmonary exercise testing and semisupine exercise echocardiography 1 h after placebo or sildenafil ingestion in a double-blind randomized crossover design. The primary efficacy end point was exercise capacity (V̇o 2peak ) while secondary measures included pulmonary vascular resistance, cardiac output, and change in PTAC. DM subjects were aged 44 ± 13 yr, 73% male, with 16 ± 10 yr DM history. Sildenafil caused marginal improvements in echocardiographic measures of biventricular systolic function in DM subjects. Exercise-induced increases in pulmonary artery systolic pressure and pulmonary vascular resistance were attenuated with sildenafil, while heart rate (+2.4 ±1.2 beats/min, P = 0.04) and cardiac output (+322 ± 21 ml, P = 0.03) improved. However, the degree of PTAC did not change ( P = 0.93) and V̇o 2peak did not increase following sildenafil as compared with placebo (V̇o 2peak : 31.8 ± 9.7 vs. 32.1 ± 9.5 ml·min −1 ·kg −1 , P = 0.42). We conclude that sildenafil administration causes modest acute improvements in central hemodynamics but does not improve exercise capacity. This may be due to the mismatch in action of sildenafil on the pulmonary arteries rather than the distal pulmonary microvasculature and potential adverse effects on peripheral oxygen extraction. NEW & NOTEWORTHY This is one of the largest and most comprehensive studies of cardiopulmonary exercise performance in people with diabetes mellitus and to our knowledge the first to assess the effect of sildenafil using detailed echocardiographic measures during incremental exercise. Sildenafil attenuated the rise in pulmonary vascular resistance while augmenting cardiac output and intriguingly heart rate, without conferring any improvement in exercise capacity. The enhanced central hemodynamic indexes may have been offset by reduced peripheral O 2 extraction.
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Roberts et al. (2019) conducted an RCT in Diabetes mellitus (n=60). Sildenafil vs. Placebo was evaluated on Exercise capacity (V̇o2peak) (p=0.42). Sildenafil administration did not improve exercise capacity (V̇o2peak 31.8 vs 32.1 ml·min−1·kg−1; P=0.42) compared with placebo in subjects with diabetes mellitus.
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