Impact of sodium-glucose co-transporter inhibitors on cardiac autonomic function and mortality: no time to die

Lim, Ven Gee; He, Hejie; Lachlan, Thomas; Ng, G A; Kyrou, Ioannis; Randeva, Harpal S.; Osman, Faizel

doi:10.1093/europace/euab321

Cited by 11 publications

(9 citation statements)

References 45 publications

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“…Both sodium–glucose transporter-2 (SGLT-2) and angiotensin-converting enzyme (ACE) inhibitors promote preventive and therapeutic effects in attenuating diabetic cardiac dysautonomia [ 25 , 46 , 47 , 48 , 49 , 50 , 51 ]. Despite the lack of SGLT-2 in the heart, studies with gliflozins demonstrated a significant reduction in cardiovascular risk and deaths consequent of DM, which could result in part from the regulation of the autonomic nervous system through the inhibition of renal reabsorption of glucose [ 47 , 50 , 52 ]. Recently, the EMBODY trial indicated that medium-term (6 months) use of empagliflozin (10 mg p.o.…”

Section: Alternative Treatment Of Dm-cardiac Autonomic Neuropathymentioning

confidence: 99%

Diabetes-Induced Cardiac Autonomic Neuropathy: Impact on Heart Function and Prognosis

et al. 2022

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Cardiovascular autonomic neuropathy (CAN) is a severe complication of the advance stage of diabetes. More than 50% of diabetic patients diagnosed with peripheral neuropathy will have CAN, with clinical manifestations including tachycardia, severe orthostatic hypotension, syncope, and physical exercise intolerance. Since the prevalence of diabetes is increasing, a concomitant increase in CAN is expected and will reduce quality of life and increase mortality. Autonomic dysfunction is associated with reduced baroreflex sensitivity and impairment of sympathetic and parasympathetic modulation. Various autonomic function tests are used to diagnose CAN, a condition without adequate treatment. It is important to consider the control of glucose level and blood pressure as key factors for preventing CAN progression. However, altered biomarkers of inflammatory and endothelial function, increased purinergic receptor expression, and exacerbated oxidative stress lead to possible targets for the treatment of CAN. The present review describes the molecular alterations seen in CAN, diagnosis, and possible alternative treatments.

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Section: Alternative Treatment Of Dm-cardiac Autonomic Neuropathymentioning

confidence: 99%

Diabetes-Induced Cardiac Autonomic Neuropathy: Impact on Heart Function and Prognosis

et al. 2022

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“…SGLT2 inhibitors may reduce sympathetic nervous activity but if this is the explanation, a similar reduction in heart rate might have been expected among patients in with sinus rhythm. 16 Alternatively, more patients may have reverted to sinus rhythm in the dapagliflozin group, compared with the placebo group given that an antiarrhythmic and beneficial effect on AF has been suggested for SGLT2 inhibitors. 28,29 Unfortunately, we did not have follow-up ECGs to confirm or refute this hypothesis.…”

Section: Discussionmentioning

confidence: 99%

“…We also examined the effect of dapagliflozin on heart rate and the effect of dapagliflozin according to heart rate across the spectrum of LVEF because there is some mainly experimental, evidence that SGLT2 (sodium-glucose cotransporter-2) inhibitors reduce cardiac sympathetic nerve activity and increase parasympathetic nervous system activity. 16,17 METHODS Data underlying the findings described in this article may be obtained following AstraZeneca's data-sharing policy described at https://astrazenecagrouptrials.pharmacm.com/ ST/Submission/Disclosure.…”

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confidence: 99%

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Efficacy of Dapagliflozin According to Heart Rate: A Patient-Level Pooled Analysis of DAPA-HF and DELIVER

Kondo,

Butt,

Curtain

et al. 2023

Circ: Heart Failure

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Background: Although elevated resting heart rate (HR) is associated with a higher risk of cardiovascular events in patients with heart failure with reduced ejection fraction in sinus rhythm (SR), the relationship between HR and outcomes among patients with heart failure with mildly reduced ejection fraction/heart failure with preserved ejection fraction and in those with atrial fibrillation (AF) is uncertain. The aims of this study were to examine the association between baseline HR and outcomes across the range of left ventricular ejection fraction, in patients with and without AF, and evaluate the effect of dapagliflozin according to HR. Methods: A patient-level pooled analysis of the DAPA-HF (Dapagliflozin and Prevention of Adverse Outcomes in Heart Failure; heart failure with reduced ejection fraction) and DELIVER (Dapagliflozin Evaluation to Improve the Lives of Patients With Preserved Ejection Fraction Heart Failure trial; heart failure with mildly reduced ejection fraction/heart failure with preserved ejection fraction) trials. The primary outcome of each was the composite of worsening heart failure or cardiovascular death. Results: Among patients with SR (n=6401, 64%), the rate of the primary outcome was higher in those with higher HR: 16.8 versus 7.7 per 100 person-years for ≥80 bpm versus <60 bpm. The relationship between HR and risk was steeper in heart failure with reduced ejection fraction versus heart failure with mildly reduced ejection fraction/heart failure with preserved ejection fraction. HR was not associated with outcomes in patients in AF for either heart failure phenotype. The benefit of dapagliflozin on the primary outcome was consistent across the HR range in both SR ( P interaction =0.28) and AF ( P interaction =0.56), for example, for SR <60 bpm, hazard ratio for dapagliflozin versus placebo 0.72 (95% CI, 0.55–0.95); 60 to 69 bpm, 0.78 (0.63–0.97); 70 to 79 bpm, 0.73 (0.59–0.91); ≥80 bpm, 0.77 (0.61–0.97). The benefit was consistent across HR range in both heart failure with reduced ejection fraction and heart failure with mildly reduced ejection fraction/heart failure with preserved ejection fraction. Conclusions: The risk of worsening heart failure or cardiovascular death increased with increasing baseline HR among patients in SR, but this association was not seen among patients in AF, irrespective of left ventricular ejection fraction. The benefit of dapagliflozin was consistent across HR range, irrespective of left ventricular ejection fraction or rhythm. REGISTRATION: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT03036124 and NCT03619213.

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“…However, this is probably opposed by the decreased sympathetic activity that results from treatment with gliflozins. A very thorough review on this topic has recently been published [ 144 ]. A review of reports to the Food and Drug Administration adverse event-reporting system revealed fewer atrial fibrillation events in patients on SGLT2 inhibitors compared to other antidiabetic drugs [ 145 ].…”

Section: Adverse Effectsmentioning

confidence: 99%

Sodium Glucose Cotransporter-2 Inhibitors: Spotlight on Favorable Effects on Clinical Outcomes beyond Diabetes

Chábová

Zakiyanov

2022

IJMS

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Sodium glucose transporter type 2 (SGLT2) molecules are found in proximal tubules of the kidney, and perhaps in the brain or intestine, but rarely in any other tissue. However, their inhibitors, intended to improve diabetes compensation, have many more beneficial effects. They improve kidney and cardiovascular outcomes and decrease mortality. These benefits are not limited to diabetics but were also found in non-diabetic individuals. The pathophysiological pathways underlying the treatment success have been investigated in both clinical and experimental studies. There have been numerous excellent reviews, but these were mostly restricted to limited aspects of the knowledge. The aim of this review is to summarize the known experimental and clinical evidence of SGLT2 inhibitors’ effects on individual organs (kidney, heart, liver, etc.), as well as the systemic changes that lead to an improvement in clinical outcomes.

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Impact of sodium-glucose co-transporter inhibitors on cardiac autonomic function and mortality: no time to die

Cited by 11 publications

References 45 publications

Diabetes-Induced Cardiac Autonomic Neuropathy: Impact on Heart Function and Prognosis

Diabetes-Induced Cardiac Autonomic Neuropathy: Impact on Heart Function and Prognosis

Efficacy of Dapagliflozin According to Heart Rate: A Patient-Level Pooled Analysis of DAPA-HF and DELIVER

Sodium Glucose Cotransporter-2 Inhibitors: Spotlight on Favorable Effects on Clinical Outcomes beyond Diabetes

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