Early effects of empagliflozin on exercise tolerance in patients with heart failure: A pilot study

Núñez, Julio; Palau, Patricia; Domínguez, Eloy; Mollar, Anna; Núñez, Eduardo; Ramón, José; Miñana, Gema; Santas, Enrique; Fácila, Lorenzo; Górriz, José Luis; Sanchís, Juan; Bayés‐Genís, Antoni

doi:10.1002/clc.22899

Cited by 29 publications

(26 citation statements)

References 12 publications

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“…Limited data are available on functional improvement of metabolic treatments in HF ( Table 2). 54–60 In a small study, a beneficial effect of metformin on peak VO 2 was not confirmed ( P = 0.08). However, a significant improvement of the slope of the ratio of minute ventilation to carbon dioxide production was present (from 32.9 ± 15.9 to 28.1 ± 8.8, P = 0.034), which reflects cellular metabolism independent of oxygen uptake and has a strong prognostic power in HF 55 .…”

Section: Co‐morbidities Of Heart Failurementioning

confidence: 94%

Improving exercise capacity and quality of life using non‐invasive heart failure treatments: evidence from clinical trials

Haehling

Arzt

Doehner

et al. 2020

European J of Heart Fail

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Endpoints of large‐scale trials in chronic heart failure have mostly been defined to evaluate treatments with regard to hospitalizations and mortality. However, patients with heart failure are also affected by very severe reductions in exercise capacity and quality of life. We aimed to evaluate the effects of heart failure treatments on these endpoints using available evidence from randomized trials. Interventions with evidence for improvements in exercise capacity include physical exercise, intravenous iron supplementation in patients with iron deficiency, and – with less certainty – testosterone in highly selected patients. Erythropoiesis‐stimulating agents have been reported to improve exercise capacity in anaemic patients with heart failure. Sinus rhythm may have some advantage when compared with atrial fibrillation, particularly in patients undergoing pulmonary vein isolation. Studies assessing treatments for heart failure co‐morbidities such as sleep‐disordered breathing, diabetes mellitus, chronic kidney disease and depression have reported improvements of exercise capacity and quality of life; however, the available data are limited and not always consistent. The available evidence for positive effects of pharmacologic interventions using angiotensin‐converting enzyme inhibitors, angiotensin receptor blockers, beta‐blockers, and mineralocorticoid receptor antagonists on exercise capacity and quality of life is limited. Studies with ivabradine and with sacubitril/valsartan suggest beneficial effects at improving quality of life; however, the evidence base is limited in particular for exercise capacity. The data for heart failure with preserved ejection fraction are even less positive, only sacubitril/valsartan and spironolactone have shown some effectiveness at improving quality of life. In conclusion, the evidence for state‐of‐the‐art heart failure treatments with regard to exercise capacity and quality of life is limited and appears not robust enough to permit recommendations for heart failure. The treatment of co‐morbidities may be important for these patient‐related outcomes. Additional studies on functional capacity and quality of life in heart failure are required.

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Section: Co‐morbidities Of Heart Failurementioning

confidence: 94%

Improving exercise capacity and quality of life using non‐invasive heart failure treatments: evidence from clinical trials

Haehling

Arzt

Doehner

et al. 2020

European J of Heart Fail

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“…However, those not on loop diuretics did not experience the same benefit. It is hypothesized that the synergistic effect of the two medications is due to increased sodium delivery to the distal tubules, which amplifies the natriuretic effect of diuretics 56,57…”

Section: Use In the Treatment Of Type 2 Diabetesmentioning

confidence: 99%

<p>Sodium-Glucose Cotransporter-2 (SGLT2) Inhibitors: A Clinician’s Guide</p>

Simes¹,

MacGregor²

2019

DMSO

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This comprehensive review covers the historical background, physiology, application in type 2 diabetes, novel uses, cardiovascular benefits, side effects and contraindications of sodium-glucose cotransporter-2 (SGLT2) inhibitors. SGLT2 inhibitors are an insulin-independent class of oral antihyperglycemic medication that clinicians use in the treatment of type 2 diabetes. Multiple landmark clinical trials support the effectiveness of SGLT2 inhibitors in reducing blood glucose levels, but it is important to understand when to properly utilize them. SGLT2 inhibitors are the most beneficial as an adjunct medication in addition to metformin in patients with a history of cardiovascular or renal disease who need further hemoglobin A1c reduction. The novel mechanism of action also demands clinicians be aware of the side effects not typically experienced with other oral antihyperglycemic drugs, such as genital tract infections, lower leg amputations, electrolyte disturbances and bone fractures. On top of their benefits in type 2 diabetes, novel uses for SGLT2 inhibitors are being uncovered. Diabetic patients with non-alcoholic fatty liver disease, who are at an increased risk of cirrhosis and hepatocellular carcinoma, experience a clinically significant reduction in serum alanine aminotransferase levels. SGLT2 inhibitors are also effective at lowering body weight in obese individuals and decreasing systolic blood pressure. Dual SGLT1/SGLT2 inhibitors are currently being investigated as possibly the first oral medication for type 1 diabetes.

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“…To date, two pilot studies have investigated whether empagliflozin improves cardiorespiratory fitness in patients with T2D with heart failure. Núñez et al[45] showed that short-term (4 wk) empagliflozin treatment increased VO 2peak by 1.21 mL/kg per minute (11.1%) from baseline. Conversely, Carbone et al[46] showed that empagliflozin treatment for 4 wk did not significantly improve VO 2peak (14.5 mL/kg vs 15.8 mL/kg per minute).…”

Section: Sglt2 Inhibitors and Cardiorespiratory Fitnessmentioning

confidence: 99%

“…Intriguingly, patients concomitantly treated with loop diuretics demonstrated improved VO 2peak (+0.9 mL/kg per minute), whereas those without loop diuretics demonstrated a decrease in VO 2peak (−0.9 mL/kg per minute). Indeed, all patients in the study by Núñez et al[45] received loop diuretics. The authors hypothesized that empagliflozin acts on the proximal renal tubules by interacting with sodium/hydrogen exchangers, thereby increasing sodium delivery at the distal renal tubules and enhancing the effect of loop diuretics[47,48].…”

Section: Sglt2 Inhibitors and Cardiorespiratory Fitnessmentioning

confidence: 99%

Effects of glucose-lowering agents on cardiorespiratory fitness

Hamasaki¹

2018

WJD

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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.

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Early effects of empagliflozin on exercise tolerance in patients with heart failure: A pilot study

Abstract: In this pilot study, empagliflozin was associated with 1-month improvement in exercise capacity in T2DM patients with symptomatic HF. This beneficial effect was also found for other surrogates of severity.

Cited by 29 publications

References 12 publications

Improving exercise capacity and quality of life using non‐invasive heart failure treatments: evidence from clinical trials

Improving exercise capacity and quality of life using non‐invasive heart failure treatments: evidence from clinical trials

<p>Sodium-Glucose Cotransporter-2 (SGLT2) Inhibitors: A Clinician’s Guide</p>

Effects of glucose-lowering agents on cardiorespiratory fitness

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