Empagliflozin, a novel potent and selective SGLT‐2 inhibitor, improves glycaemic control alone and in combination with insulin in streptozotocin‐induced diabetic rats, a model of type 1 diabetes mellitus

Luippold, Gerd; Klein, Thomas; Michael, Mark; Grempler, Rolf

doi:10.1111/j.1463-1326.2012.01569.x

Cited by 67 publications

(62 citation statements)

References 33 publications

(45 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The increase in insulin plasma levels in ZDF rats with different SGLT2i drugs is well documented [25,[46][47][48][49]. Of importance is that empagliflozin was shown to lower blood glucose levels (thereby sparing insulin) in a preclinical model of streptozotocin-induced type 1 diabetes [50] and also in human studies [51,52]. SGLT2i treatment appears to be highly efficient in preventing glucotoxicity, i.e.…”

Section: Discussionmentioning

confidence: 99%

The SGLT2 Inhibitor Empagliflozin Improves the Primary Diabetic Complications in ZDF Rats

Hanf

Steven

Oelze

et al. 2017

Free Radical Biology and Medicine

View full text Add to dashboard Cite

A B S T R A C THyperglycemia associated with inflammation and oxidative stress is a major cause of vascular dysfunction and cardiovascular disease in diabetes. Recent data reports that a selective sodium-glucose co-transporter 2 inhibitor (SGLT2i), empagliflozin (Jardiance ® ), ameliorates glucotoxicity via excretion of excess glucose in urine (glucosuria) and significantly improves cardiovascular mortality in type 2 diabetes mellitus (T2DM). The overarching hypothesis is that hyperglycemia and glucotoxicity are upstream of all other complications seen in diabetes. The aim of this study was to investigate effects of empagliflozin on glucotoxicity, β-cell function, inflammation, oxidative stress and endothelial dysfunction in Zucker diabetic fatty (ZDF) rats. Male ZDF rats were used as a model of T2DM (35 diabetic ZDF-Lepr fa/fa and 16 ZDF-Lepr +/+ controls). Empagliflozin (10 and 30 mg/kg/d) was administered via drinking water for 6 weeks. Treatment with empagliflozin restored glycemic control. Empagliflozin improved endothelial function (thoracic aorta) and reduced oxidative stress in the aorta and in blood of diabetic rats. Inflammation and glucotoxicity (AGE/RAGE signaling) were epigenetically prevented by SGLT2i treatment (ChIP). Linear regression analysis revealed a significant inverse correlation of endothelial function with HbA1c, whereas leukocyte-dependent oxidative burst and C-reactive protein (CRP) were positively correlated with HbA1c. Viability of hyperglycemic endothelial cells was pleiotropically improved by SGLT2i. Empagliflozin reduces glucotoxicity and thereby prevents the development of endothelial dysfunction, reduces oxidative stress and exhibits anti-inflammatory effects in ZDF rats, despite persisting hyperlipidemia and hyperinsulinemia. Our preclinical observations provide insights into the mechanisms by which empagliflozin reduces cardiovascular mortality in humans (EMPA-REG trial).

show abstract

Section: Discussionmentioning

confidence: 99%

The SGLT2 Inhibitor Empagliflozin Improves the Primary Diabetic Complications in ZDF Rats

Hanf

Steven

Oelze

et al. 2017

Free Radical Biology and Medicine

View full text Add to dashboard Cite

show abstract

“…Some of the important studies demonstrated that empagliflozin enhances the urinary glucose excretion with concomitant reductions in the fasting and postprandial glucose levels and glycated hemoglobin (HbA1c) in Zukar Diabetic Fatty (ZDF) rats [47,48]. One important study [49] showed the significance of combinatorial therapy of empagliflozin with insulin in type-1 diabetes mellitus (T1DM) rats. The research work clearly revealed that addition of empagliflozin to insulin pre-treated rats causes prolonged reductions in hyperglycemia, without any episode of hypoglycemia.…”

Section: Empagliflozinmentioning

confidence: 99%

An Emerging Protagonist: Sodium Glucose Co-transporters (SGLTs) as a Burgeoning Target for the Treatment of Diabetes Mellitus

et al. 2014

View full text Add to dashboard Cite

“…Empagliflozin increased urinary glucose excretion (UGE) and improved glycemic control in streptozotocin-induced T1D rats. 10,11 In T1D mice, empagliflozin treatment significantly improved glucose tolerance with improvements in mRNA and serum insulin levels. 10 The authors hypothesized that empagliflozin may help in the preservation of β-cell mass, evidenced by reduction in β-cell apoptosis and stimulation of β-cell proliferation, possibly due to protection of β-cells from glucotoxicity-induced oxidative stress.…”

Section: Clinical Evidence With Sodium-glucose Co-transporter-2 Inhibmentioning

confidence: 99%

“…The prevalence of overweight and obesity among newly diagnosed T1D subjects was 21-22% in the [2][3][4][5][6][7][8][9][10][11][12][13][14][15][16][17][18][19] year age group in the Pediatric Diabetes Consortium and the SEARCH for Diabetes in Youth study. 1,2 This has been attributed to a general worldwide increase in prevalence of obesity and similar risk factors such as family history, ethnicity, and sedentary lifestyle may be contributory.…”

mentioning

confidence: 99%

Sodium-glucose Co-transporter-2 Inhibitors in Type 1 Diabetes—a Dangerous Ally

Priya¹,

Kalra²,

Bhambri³

2017

US Endocrinology

View full text Add to dashboard Cite

There is an unmet need for adjunctive non-insulin-based therapies in type 1 diabetes (T1D). Weight gain, recurrent hypoglycemia and suboptimal glycemic control remain significant challenges. Sodium-glucose co-transporter-2 (SGLT2) inhibitors and dual inhibitors of sodium-glucose co-transporter-1 (SGLT1) and SGLT2 may have a potential role as an add-on therapy to insulin. The benefits include improved glycemic control, weight reduction, and reduced insulin dose requirement. However, the risk of diabetic ketoacidosis with SGLT2 inhibitors is significant and the diagnosis may be delayed due to absence of significant hyperglycemia. At present, SGLT2 inhibitors are not approved for use in T1D, and the risks should be discussed at length with the patient. We propose strategies to minimize the risk of diabetic ketoacidosis associated with off-label use of SGLT2 inhibitors in T1D.

show abstract

Empagliflozin, a novel potent and selective SGLT‐2 inhibitor, improves glycaemic control alone and in combination with insulin in streptozotocin‐induced diabetic rats, a model of type 1 diabetes mellitus

Cited by 67 publications

References 33 publications

The SGLT2 Inhibitor Empagliflozin Improves the Primary Diabetic Complications in ZDF Rats

The SGLT2 Inhibitor Empagliflozin Improves the Primary Diabetic Complications in ZDF Rats

An Emerging Protagonist: Sodium Glucose Co-transporters (SGLTs) as a Burgeoning Target for the Treatment of Diabetes Mellitus

Sodium-glucose Co-transporter-2 Inhibitors in Type 1 Diabetes—a Dangerous Ally

Contact Info

Product

Resources

About