Effects of pioglitazone with and without exercise training on cardiorespiratory fitness and oxygen uptake kinetics in type 2 diabetes

Aims Exercise tolerance is often impaired in type 2 diabetes (T2D), and barriers to regular exercise are common. This study evaluated whether 12 weeks of pioglitazone (PIO) therapy could enhance peak oxygen uptake (V̇O 2peak ) and the time constant of the primary phase of oxygen uptake (τV̇O 2p ) during submaximal exercise, compared with exercise training, and whether combining PIO with exercise would provide additional benefits in T2D. Materials and Methods Male participants with T2D were assigned to one of the following groups: (1) non‐exercising control ( CON , n = 12), (2) PIO (15 mg/day) alone ( PIO , n = 6), (3) exercise training alone ( EXC , n = 13), or (4) PIO combined with exercise ( PIO + EXC , n = 7). Exercise involved aerobic and resistance training three times per week for 12 weeks. V̇O 2peak (incremental cycling) and τV̇O 2p , mean arterial pressure, and cardiac output (inert gas re‐breathing) during cycling were assessed pre‐ and post‐intervention. Results PIO and PIO + EXC groups showed reductions ( p < 0.01) in glycated haemoglobin (HbA 1c ). V̇O 2peak increased ( p < 0.05) and τV̇O 2p decreased ( p < 0.01) in both the EXC (V̇O 2peak : 2.44 ± 0.38 to 2.73 ± 0.42 L·min −1 ; τV̇O 2p : 42.7 ± 6.2 to 34.3 ± 7.2 s) and PIO + EXC (V̇O 2peak : 2.66 ± 0.43 to 2.88 ± 0.42 L·min −1 ; τV̇O 2p : 40.3 ± 10.6 to 32.7 ± 8.3 s) groups. The magnitude of these effects was not different between the exercising groups. PIO alone did not induce changes in V̇O 2peak or τV̇O 2p . Neither exercise nor PIO altered systemic cardiovascular dynamics. Conclusions Although PO improved glycaemic control, it did not enhance aerobic exercise capacity or V̇O 2 kinetics. Moreover, in combination with exercise training, PIO did not provide additional benefits beyond those achieved through exercise alone.