The effect of SGLT-2 inhibitors on cardiorespiratory fitness capacity: A systematic review and meta-analysis

Objective: The study aimed to evaluate the effect of sodium–glucose transporter 2 (SGLT-2) inhibitors on various parameters of exercise capacity and provide an evidence-based basis for type 2 diabetes mellitus (T2DM) combined with heart failure (HF) patients or HF patients without T2DM who use SGLT-2 inhibitors to improve cardiorespiratory fitness (CRF). Methods: According to the participant, intervention, comparison, and outcome (PICO) elements, the effects of SGLT-2 inhibitor administration on VO(2) or VO(2)peak were researched in this study. Weighted mean difference (WMD) and 95% confidence intervals (CIs) were calculated (random-effects model). Heterogeneity was assessed by the I(2) test. Results: Six studies were included according to the eligibility criteria: four were RCTs, and two were non-RCTs. Compared with the control group, the merge results of RCTs showed that SGLT-2 inhibitors could significantly increase the VO(2)peak (WMD, 2.02 ml kg(−1) min(−1), 95% CI: 0.68–3.37, and p = 0.03; I(2) = 0% and p = 0.40) and VAT (WMD, 1.57 ml kg(−1) min(−1), 95% CI: 0.06–3.07, and p = 0.04; I(2) = 0% and p = 0.52) of the obese population, patients with T2DM, and chronic HF patients with or without T2DM. Subgroup analysis showed that SGLT-2 inhibitors improved the VO(2)peak in non-HF patients (WMD, 3.57 ml kg(−1) min(−1), 95% CI: 0.87–6.26, and p = 0.009; I(2) = 4% and p = 0.31) more than in HF patients (WMD, 1.46 ml kg(−1) min(−1), 95% CI: −0.13–3.04, and p = 0.07; I(2) = 0% and p = 0.81). Moreover, the merge of single-arm studies also indicated that empagliflozin could improve VO(2)peak (MD, 1.11 ml kg(−1) min(−1), 95% CI: 0.93–1.30, and p = 0.827, Δ p = 0.000 and I(2) = 0%) of T2DM patients with chronic HF. Conclusion: Despite the limited number of studies and samples involved, the meta-analysis preliminarily demonstrated that SGLT-2 inhibitors could improve some parameters of exercise capacity (VO(2)peak, VAT) in chronic HF patients with or without T2DM and obese individuals, which had a positive effect on promoting cardiopulmonary fitness to help these populations improve their prognosis. Systematic Review Registration: [https://www.crd.york.ac.uk/prospero/#recordDetails], identifier [CRD42020202788].