Pioglitazone Improves Blood Sugar but Only Exercise Boosts Fitness in Type 2 Diabetes: Study Finds
Ireland: A recent study published in Diabetes, Obesity and Metabolism has found that while the diabetes medication pioglitazone (PIO) can significantly improve blood sugar control, it does not enhance aerobic capacity or oxygen uptake kinetics in men with type 2 diabetes (T2D). Moreover, when combined with exercise training, pioglitazone offers no additional gains in exercise performance beyond those provided by exercise alone.
The research, led by Dr. Mikel Egaña and colleagues from the Department of Physiology at Trinity College Dublin's School of Medicine, aimed to address a key issue for people with T2D: impaired exercise tolerance. The team sought to determine whether a 12-week course of pioglitazone could boost peak oxygen uptake (V̇O₂peak) and improve the time constant of oxygen uptake (τV̇O₂p) during submaximal exercise, either alone or in combination with exercise training.
The study involved male participants with T2D divided into four groups: a non-exercising control group, a pioglitazone-only group (15 mg/day), an exercise-only group, and a group combining pioglitazone with exercise. The exercise regimen included both aerobic and resistance training three times per week over the 12-week period. Researchers measured aerobic capacity through incremental cycling tests, along with cardiovascular parameters such as mean arterial pressure and cardiac output.
The study led to the following findings:
- Both the pioglitazone-only and pioglitazone-plus-exercise groups showed significant reductions in glycated haemoglobin (HbA1c), indicating the drug’s effectiveness in lowering blood sugar.
- Improvements in peak oxygen uptake (V̇O₂peak) and oxygen uptake time constant (τV̇O₂p) occurred only in the exercise-only and exercise-plus-pioglitazone groups.
- In these exercise groups, aerobic capacity increased and oxygen uptake kinetics improved.
- The degree of improvement in exercise performance was similar whether or not pioglitazone was combined with exercise.
- Pioglitazone alone did not result in measurable changes in aerobic performance or cardiovascular dynamics.
The authors note that their findings emphasize the importance of physical activity for improving exercise tolerance in T2D. While pioglitazone remains an effective tool for glycaemic control, it should not be relied upon to enhance aerobic fitness. “Our results suggest that to improve exercise performance, men with uncomplicated type 2 diabetes taking pioglitazone should also engage in regular structured exercise,” the researchers concluded.
The study acknowledges certain limitations, including a relatively small sample size, lack of placebo control, and the inclusion of only male participants due to slower female recruitment. Although two women completed the combined pioglitazone-and-exercise protocol, incorporating their data did not alter the overall outcomes. Future randomized controlled trials, the authors recommend, should explore possible sex-specific effects of pioglitazone and assess longer-term impacts, including changes in body composition and post-intervention follow-up.
Ultimately, the research reinforces a consistent message in diabetes care: while medication is essential for managing blood sugar, regular exercise remains the cornerstone for improving cardiovascular fitness and overall health in individuals with type 2 diabetes.
Reference:
O'Connor E, Kiely C, Gildea N, O'Shea D, Green S, Egaña M. Effects of pioglitazone with and without exercise training on cardiorespiratory fitness and oxygen uptake kinetics in type 2 diabetes. Diabetes Obes Metab. 2025 Jul 30. doi: 10.1111/dom.16648. Epub ahead of print. PMID: 40735972.
