SGLT2 Inhibition with Empagliflozin Increases Circulating Provascular Progenitor Cells in People with Type 2 Diabetes Mellitus

Hess, David A.; Terenzi, Daniella C.; Trac, Justin Z.; Quan, Adrian; Mason, Tamique; Al‐Omran, Mohammed; Bhatt, Deepak L.; Dhingra, Natasha; Rotstein, Ori D.; Leiter, Lawrence A.; Zinman, Bernard; Sabongui, Sandra; Yan, Andrew T.; Teoh, Hwee; Mazer, C. David; Connelly, Kim A.; Verma, Subodh

doi:10.1016/j.cmet.2019.08.015

Cited by 82 publications

(47 citation statements)

References 15 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…113 Conversely, Hess and colleagues have recently reported that a therapy with empagliflozin can increase Aldehyde dehydrogenase-expressing cells. 114 Unfortunately, the identify of these cells is still unclear, as is their role in T2D complications, such that there is so far no evidence that cardiorenal protection by SGLT2i can be attributed to effects on regenerative circulating stem/progenitor cells.…”

Section: Epicardial Adipose Tissue Volumementioning

confidence: 99%

<p>Extraglycemic Effects of SGLT2 Inhibitors: A Review of the Evidence</p>

Bonora

Avogaro

Fadini

2020

DMSO

131

View full text Add to dashboard Cite

Patients with type 2 diabetes (T2D) are often overweight/obese and affected by arterial hypertension, dyslipidaemia, and have high serum levels of uric acid. Moreover, T2D patient have a higher risk of developing cardiovascular or renal complications, which are leading causes of morbidity and mortality in this population. Sodium-glucose cotransporter-2 inhibitors (SGLT2i) are a new class of glucose-lowering medications that block the reabsorption of glucose in the kidney, thereby increasing urinary glucose excretion, and lowering blood glucose levels. The beneficial effects of SGLT2 inhibition extend beyond glycaemic control, and include improvement in blood pressure, body weight, uric acid concentrations, liver steatosis, oxidative stress, and inflammation. In dedicated cardiovascular outcome trials, SGLT2i treatment was associated with a significant reduction in the rate of cardiovascular events and renal endpoints. In this review, we summarize the evidence for extra-glycemic effects of SGLT2i and the potential mechanisms driving cardiorenal protection exerted by this class of medications.

show abstract

Section: Epicardial Adipose Tissue Volumementioning

confidence: 99%

<p>Extraglycemic Effects of SGLT2 Inhibitors: A Review of the Evidence</p>

Bonora

Avogaro

Fadini

2020

DMSO

131

View full text Add to dashboard Cite

show abstract

“…Clinical trials examining the cardiovascular and renal effects of SGLT2 inhibitors have shown that this class of antihyperglycemic agents is beneficial for patients with type 2 diabetes and/or heart failure [ [1] , [2] , [3] , [4] ]. Accordingly, there is tremendous interest to elucidate the mechanisms responsible for these benefits [ [10] , [11] , [12] , [13] , [14] , [15] , [16] , [17] , [18] ]. In the context of a randomized trial, the present analysis explores the impact of empagliflozin (vs. placebo) on cardiac autonomic activity.…”

Section: Discussionmentioning

confidence: 99%

Does empagliflozin modulate the autonomic nervous system among individuals with type 2 diabetes and coronary artery disease? The EMPA-HEART CardioLink-6 Holter analysis

et al. 2020

Self Cite

View full text Add to dashboard Cite

Context We examined if empagliflozin was associated with modulation of cardiac autonomic tone among subjects with type 2 diabetes and stable coronary artery disease (CAD) relative to placebo. Methods Using ambulatory 24-h Holter electrocardiographic data prospectively collected from a randomized trial, we compared changes in heart rate variability (HRV) parameters between empagliflozin- and placebo-assigned subjects over a follow-up period of 6 months. Measured HRV domains included: standard deviation (SD) of NN intervals (SDNN), SD of average NN intervals per 5-min (SDANN), root mean square of successive RR interval differences (RMSSD), % successive NN intervals differing >50 ms (ms) (pNN50), low frequency (LF), high frequency (HF) and the LF/HF ratio (LF:HF). Differences in HRV parameters between the 2 groups were compared with analysis of covariance (ANCOVA). Statistical measures of significance were reported as adjusted differences between the 2 groups and their corresponding 95% confidence intervals. Results Sixty-six subjects completed 24-h Holter monitoring at baseline and 6-months. Over 6 months, the change in HRV was similar between subjects treated with empagliflozin vs. placebo for the following parameters: RMSSD -1.2 ms (-6.0 to 3.6 ms); pNN50 0.5% (-2.6 to 3.6%); VLF -907.8 ms 2 (-2388.8 to 573.1 ms 2 ); LF -341 ms 2 (-878.7 to 196.7 ms 2 ); HF -33.8 ms 2 (-111.1 to 43.5 ms 2 ); LF:HF -0.1 (-0.4 to 0.2). Subjects who received placebo experienced an increase in SDNN 18.6 ms (2.8–34.3 ms) and SDANN 20.2 ms (3.2–37.3 ms) relative to those treated with empagliflozin. Conclusion Compared to placebo, empagliflozin did not result in changes in autonomic tone among individuals with type 2 diabetes and stable coronary artery disease.

show abstract

“…T2DM-associated regenerative cell depletion, which may contribute to the MACE benefit observed in clinical trials (104).…”

Section: Improvement In Vascular Progenitor Cellsmentioning

confidence: 99%

Mechanisms by Which Glucagon-Like-Peptide-1 Receptor Agonists and Sodium-Glucose Cotransporter-2 Inhibitors Reduce Cardiovascular Risk in Adults With Type 2 Diabetes Mellitus

Sharma

Verma

2020

Canadian Journal of Diabetes

Self Cite

View full text Add to dashboard Cite

Some glucagon-like-peptide-1 (GLP-1) receptor agonists and sodium-glucose cotransporter-2 (SGLT-2) inhibitors have demonstrated efficacy in reducing the risk of cardiovascular outcomes. There are extensive overlapping and distinct mechanisms of action for each class of drugs. GLP-1 receptor agonists mechanisms of action appear to reduce atherothrombotic outcomes, whereas SGLT-2 inhibitors mechanisms of action preferentially target heart failure outcomes.

show abstract

SGLT2 Inhibition with Empagliflozin Increases Circulating Provascular Progenitor Cells in People with Type 2 Diabetes Mellitus

Cited by 82 publications

References 15 publications

<p>Extraglycemic Effects of SGLT2 Inhibitors: A Review of the Evidence</p>

<p>Extraglycemic Effects of SGLT2 Inhibitors: A Review of the Evidence</p>

Does empagliflozin modulate the autonomic nervous system among individuals with type 2 diabetes and coronary artery disease? The EMPA-HEART CardioLink-6 Holter analysis

Mechanisms by Which Glucagon-Like-Peptide-1 Receptor Agonists and Sodium-Glucose Cotransporter-2 Inhibitors Reduce Cardiovascular Risk in Adults With Type 2 Diabetes Mellitus

Contact Info

Product

Resources

About