Effects of glucose-lowering agents on cardiorespiratory fitness

Exercise therapy is essential for the management of type 2 diabetes (T2D). However, patients with T2D show lower physical activity and reduced cardiorespiratory fitness than healthy individuals. It would be ideal for clinicians to co-prescribe glucose-lowering agents that improve cardiorespiratory fitness or exercise capacity in conjunction with exercise therapy. Metformin does not improve cardiorespiratory fitness and may attenuate any beneficial effect of exercise in patients with T2D. In contrast, thiazolidinediones appear to improve cardiorespiratory fitness in patients with T2D. Although evidence is limited, sodium–glucose cotransporter 2 (SGLT2) inhibitors may improve cardiorespiratory fitness in patients with heart failure, and the effect of glucagon-like peptide-1 (GLP-1) receptor agonists on cardiorespiratory fitness is controversial. Recent clinical trials have shown that both SGLT2 inhibitors and GLP-1 receptor agonists exert a favorable effect on cardiovascular disease. It becomes more important to choose drugs that have beneficial effects on the cardiovascular system beyond glucose-lowering effects. Further studies are warranted to determine an ideal glucose-lowering agent combined with exercise therapy for the treatment of T2D.