scholarly journals New SGLT2 inhibitor ertugliflozin: safe and effective in the management of type 2 diabetes

2020 ◽  
pp. 32-41
Author(s):  
V. V. Salukho ◽  
T. A. Ilyinskay
Keyword(s):  
Type 2 Diabetes ◽  
Body Mass ◽  
Clinical Studies ◽  
Sglt2 Inhibitor ◽  
Evidence Base ◽  
Sglt2 Inhibitors ◽  
Adverse Outcomes ◽  
Positive Effects ◽  
Sodium Glucose Cotransporter

Type 2 diabetes mellitus (T2DM) is closely associated with the risk of developing cardiovascular complications. A new approach to treatment of T2DM, based on the inhibition of the sodium-glucose cotransporter type 2 (SGLT2) ensures reliable insulin-independent glycemic control with quick overcome of glucotoxicity, reduction of insulin resistance, and positive effects on body mass, blood pressure and other rates. Besides, pronounces clinical efficacy of SGLT2 inhibitor is marked by its use safety and minimized frequency of adverse events. Along with this, the results of carried-out, randomized clinical studies of cardiovascular safety of different SGLT2 inhibitors showed, that apart from bearing on the risk factors, the inhibition of sodium-glucose cotransporter type 2 leads to cardioand renoprotective effects. In addition, their influence on cardiovascular and renal outcomes is the stronger the more different the pre-existing status of cardiovascular diseases of the patient is, the condition of his renal function and the severity of albuminuria. This article summarizes the main results of carried-out randomized clinical studies of SGLT2 inhibitors, which demonstrate their cardiovascular advantages and compile encouraging results of multicentered studies VERTIS, examining different aspects of the use of the ertugliflazine SGLT2 inhibitor in patients with type 2 diabetes. There is data provided demonstrating a powerful glucoselowering, body-mass lowering and hypotensive impacts of ertugliflazine comparable to the same performance of the best representatives of the class. This article describes an evidence base of the use of the drug in monotherapy and its ability to be combined with other oral hypoglycemic agentsand highlightes a high level of safety of the use of ertugliflazine correspondinding to minimized frequency of adverse outcomes of SGLT2 inhibition and so the potential of SGLT2 inhibitors as a new promising class for the treatment of patients with type 2 diabetes and established cardiovascular disease is revealed.

scholarly journals Impact of sodium–glucose cotransporter 2 inhibitors on renal function in participants with type 2 diabetes and chronic kidney disease with normoalbuminuria

2020 ◽  
Vol 12 (1) ◽  
Author(s):  
Akinobu Nakamura ◽  
Hideaki Miyoshi ◽  
Hiraku Kameda ◽  
Kumiko Yamashita ◽  
Yoshio Kurihara
Keyword(s):  
Type 2 Diabetes ◽  
Chronic Kidney Disease ◽  
Renal Function ◽  
Kidney Disease ◽  
Sglt2 Inhibitor ◽  
Sglt2 Inhibitors ◽  
Creatinine Ratio ◽  
Sodium Glucose Cotransporter ◽  
Clinical Records

Abstract Background We compared the effects of sodium–glucose cotransporter 2 (SGLT2) inhibitors on renal function in participants with type 2 diabetes and chronic kidney disease (CKD) classified by degree of albuminuria. Methods A retrospective review of the clinical records of Japanese participants with type 2 diabetes (age > 20 years; SGLT2 inhibitor treatment > 2 years; estimated glomerular filtration rate (eGFR) < 60 mL/min/1.73 m2) was conducted. Based on the urinary albumin-to-creatinine ratio (UACR) or urinary protein-to-creatinine ratio (UPCR) at the start of SGLT2 inhibitor administration, participants were categorized into three groups: normoalbuminuria (A1; UACR < 30 mg/g Cr or UPCR < 0.15 g/g Cr), microalbuminuria (A2; UACR 30 to < 300 mg/g Cr or UPCR 0.15 to < 0.50 g/g Cr), and macroalbuminuria (A3; UACR ≥ 300 mg/g Cr or UPCR ≥ 0.50 g/g Cr). The study outcome was a comparison of the rates of change in renal function evaluated by eGFR at 2 years after starting SGLT2 inhibitor among the three groups. Results A total of 87 participants (40 females, 47 males) were categorized into three groups: A1 (n = 46), A2 (n = 25), and A3 (n = 16). eGFR was similarly decreased at 2 years before starting SGLT2 inhibitor in all three groups. However, the decline in eGFR was ameliorated at 2 years after starting SGLT2 inhibitor, and eGFR was rather increased in the A1 and A2 groups. Interestingly, the rate of change in eGFR at 2 years after starting SGLT2 inhibitor in the A1 group was significantly higher than that in the A3 group. Conclusions These results demonstrate that more favorable effects of SGLT2 inhibitors on renal function were observed in participants with type 2 diabetes and CKD with normoalbuminuria compared with those with macroalbuminuria. Trial registration UMIN-CTR: UMIN000035263. Registered 15 December 2018

scholarly journals The Effect of Long-term Sodium-glucose Cotransporter 2 Inhibitor Treatment on Renal Function in the Patients with Type 2 Diabetes

2020 ◽  
Vol 95 (4) ◽  
pp. 236-243
Author(s):  
Jong Ha Baek ◽  
Tae Jung Oh ◽  
Ju-Young Moon ◽  
Taehee Kim ◽  
Seung Hyu Ko ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Renal Function ◽  
Kidney Disease ◽  
Sglt2 Inhibitor ◽  
Sglt2 Inhibitors ◽  
Renal Outcomes ◽  
Sodium Glucose Cotransporter ◽  
Inhibitor Treatment

Chronic kidney disease is developed commonly in type 2 diabetes mellitus (T2DM) and is the most common cause of end-stage renal disease and related cardiovascular complications. Meanwhile, despite the current standard of care including optimized glucose control and the use of single-agent blockade of the renin-angiotensin-aldosterone system (RAAS), patients with T2DM remain at increased risk for death and complications from cardiorenal causes. The recent studies using sodium-glucose cotransporter 2 (SGLT2) inhibitors have shown not only glucose lowering effect, but also a reduction in blood pressure, weight loss, and a lowering cardiovascular risk. Regarding renal outcomes, the use of SGLT2 inhibitor slows the progression of kidney disease compared to placebo when added to standard care. However, concern has been raised that currently available SGLT2 inhibitors in Korea may be also associated with improved renal outcomes with long-term treatment. As a result, we aimed to evaluate the effect of long-term SGLT2 inhibitor treatment on renal function in the patients with T2DM using meta-analysis. (Korean J Med 2020;95:236-243)

scholarly journals Roles of sodium-glucose cotransporter 2 of mesangial cells in diabetic kidney disease

2021 ◽  
Author(s):  
Masanori Wakisaka ◽  
Kuniyuki Nakamura ◽  
Toshiaki Nakano ◽  
Takanari Kitazono
Keyword(s):  
Type 2 Diabetes ◽  
Diabetic Nephropathy ◽  
Kidney Disease ◽  
Mesangial Cells ◽  
Sglt2 Inhibitor ◽  
Sglt2 Inhibitors ◽  
Urine Sodium ◽  
Sodium Glucose Cotransporter ◽  
Urine Sodium Excretion

Abstract We have been studying the presence of sodium-glucose cotransporter 2 (SGLT2) in mesangial cells and pericytes since 1992. Recent large placebo-controlled studies of SGLT2 inhibitors in patients with type 2 diabetes mellitus have reported desirable effects of the inhibitors on the diabetic kidney and the diabetic heart. Most studies have indicated that these effects of SGLT2 inhibitors could be mediated by the tubuloglomerular feedback (TGF) system. However, a recent study about urine sodium excretion in the presence of an SGLT2 inhibitor did not show any increases in urine sodium excretion. A very small dose of an SGLT2 inhibitor did not inhibit SGLT2 at the S1 segment of proximal tubules. Moreover, SGLT2 inhibition protects against progression in chronic kidney disease with and without type 2 diabetes. In these circumstances, the TGF hypothesis involves several theoretical concerns that must be clarified. The presence of SGLT2 in mesangial cells seems to be very important for diabetic nephropathy. We now propose a novel mechanism by which the desirable effects of SGLT2 inhibitors on diabetic nephropathy are derived from the direct effect on SGLT2 expressed in mesangial cells.

scholarly journals Potential mechanisms underlying cardiovascular protection by sodium glucose cotransporter 2 inhibitors (empagliflozin)

2021 ◽  
Vol 10 (3) ◽  
pp. 79-89
Author(s):  
I. S. Sabirov ◽  
I. T. Murkamilov ◽  
V. V. Fomin
Keyword(s):  
Type 2 Diabetes ◽  
Cardiovascular Risk ◽  
Cardiovascular Diseases ◽  
Sglt2 Inhibitor ◽  
Sglt2 Inhibitors ◽  
Controlled Clinical Trial ◽  
Sodium Glucose Cotransporter ◽  
Pubmed Database ◽  
Urinary Glucose

The presented literature review is devoted to the cardioprotective capabilities of a new class of antihyperglycemic drugs - sodium-glucose cotransporter 2 inhibitors (SGLT2), which improve glycemic control through an insulin-independent mechanism of action associated with an increase in urinary glucose excretion. The article presents the results of large-scale clinical trials on the use of SGLT2 inhibitors in patients with and without diabetes, and with cardiovascular diseases or multiple cardiovascular risk factors. A number of the most frequently discussed cardiac specific mechanisms mediated by the SGLT2 inhibitor affecting the Abstract           state of the cardiovascular system are presented. Moreover, the article presents the results of a placebo-controlled clinical trial entitled “Empagliflozin reduces mortality in patients with type 2 diabetes at high cardiovascular risk” (EMPA-REG oUtcOmE) to analyze the cardioprotective capabilities of SGLT2 inhibitor empagliflozin in patients with type 2 diabetes and concomitant cardiovascular diseases. The article emphasizes the importance of further research to determine the degree of contribution of the above-mentioned mechanisms to the cardioprotective potential of SGLT2 inhibitors. PubMed database was used to identify relevant studies and systematic reviews.

scholarly journals Euglycemic Diabetic Ketoacidosis Secondary to Dapagliflozin in a Patient with Colon Malignancy

2019 ◽  
Vol 2019 ◽  
pp. 1-4 ◽  
Author(s):  
Eleni Papadokostaki ◽  
Evangelos Liberopoulos
Keyword(s):  
Type 2 Diabetes ◽  
Adverse Effect ◽  
Colon Cancer ◽  
Diabetic Ketoacidosis ◽  
Sglt2 Inhibitor ◽  
Sglt2 Inhibitors ◽  
Sodium Glucose Cotransporter ◽  
Euglycemic Diabetic Ketoacidosis ◽  
Type 2 Diabetic

The use of sodium-glucose cotransporter 2 (SGLT2) inhibitors for the treatment of type 2 diabetes is steadily increasing. SGLT2 inhibitors are associated with weight loss, lowering of blood pressure, and low hypoglycemia risk along with beneficial cardiovascular and renoprotective effects. In view of the increasing use of SGLT2i, physicians must be aware of their adverse effects. Euglycemic diabetic ketoacidosis (euDKA) is a well-recognized adverse effect of SGLT2i. We present here a case of euglycemic diabetic ketoacidosis secondary to dapagliflozin use in a type 2 diabetic patient with colon cancer. To the best of our knowledge, this is first report of SGLT2 inhibitor-associated euDKA in a patient with underlying colon cancer.

Mechanisms of Protective Effects of SGLT2 Inhibitors in Cardiovascular Disease and Renal Dysfunction

2019 ◽  
Vol 19 (20) ◽  
pp. 1818-1849 ◽  
Author(s):  
Ban Liu ◽  
Yuliang Wang ◽  
Yangyang Zhang ◽  
Biao Yan
Keyword(s):  
Diabetes Mellitus ◽  
Heart Failure ◽  
Type 2 Diabetes ◽  
Type 2 Diabetes Mellitus ◽  
Renal Dysfunction ◽  
Sglt2 Inhibitors ◽  
Sodium Glucose Cotransporter ◽  
Glucose Reabsorption ◽  
Renal Glucose Reabsorption

: Type 2 diabetes mellitus is one of the most common forms of the disease worldwide. Hyperglycemia and insulin resistance play key roles in type 2 diabetes mellitus. Renal glucose reabsorption is an essential feature in glycaemic control. Kidneys filter 160 g of glucose daily in healthy subjects under euglycaemic conditions. The expanding epidemic of diabetes leads to a prevalence of diabetes-related cardiovascular disorders, in particular, heart failure and renal dysfunction. Cellular glucose uptake is a fundamental process for homeostasis, growth, and metabolism. In humans, three families of glucose transporters have been identified, including the glucose facilitators GLUTs, the sodium-glucose cotransporter SGLTs, and the recently identified SWEETs. Structures of the major isoforms of all three families were studied. Sodium-glucose cotransporter (SGLT2) provides most of the capacity for renal glucose reabsorption in the early proximal tubule. A number of cardiovascular outcome trials in patients with type 2 diabetes have been studied with SGLT2 inhibitors reducing cardiovascular morbidity and mortality. : The current review article summarises these aspects and discusses possible mechanisms with SGLT2 inhibitors in protecting heart failure and renal dysfunction in diabetic patients. Through glucosuria, SGLT2 inhibitors reduce body weight and body fat, and shift substrate utilisation from carbohydrates to lipids and, possibly, ketone bodies. These pleiotropic effects of SGLT2 inhibitors are likely to have contributed to the results of the EMPA-REG OUTCOME trial in which the SGLT2 inhibitor, empagliflozin, slowed down the progression of chronic kidney disease and reduced major adverse cardiovascular events in high-risk individuals with type 2 diabetes. This review discusses the role of SGLT2 in the physiology and pathophysiology of renal glucose reabsorption and outlines the unexpected logic of inhibiting SGLT2 in the diabetic kidney.

scholarly journals Advantages of therapy with sodium glucose cotransporter type 2 inhibitors in patients with type 2 diabetes mellitus in combination with hyperuricemia and gout

2020 ◽  
Vol 92 (5) ◽  
pp. 110-118 ◽  
Author(s):  
T. S. Panevin ◽  
M. S. Eliseev ◽  
M. V. Shestakova ◽  
E. L. Nasonov
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Metabolic Syndrome ◽  
Type 2 Diabetes Mellitus ◽  
New Drugs ◽  
Positive Effects ◽  
The Metabolic Syndrome ◽  
Sodium Glucose Cotransporter ◽  
The Russian Federation

Currently, only two drugs for reducing uric acid (UA), allopurinol and febuxostat, are registered in the Russian Federation, but their use does not allow to achieve the target level of UA in all cases. According to the results of numerous randomized trials, hyperuricemia and gout are associated with the corresponding components of the metabolic syndrome, including diabetes mellitus. The influence of factors is due to the need to search for new drugs that have a complex effect on several components of metabolic syndrome at once. Potentially attractive in this regard is a new group of drugs for the treatment of type 2 diabetes mellitus inhibitors of the sodium-glucose cotransporter of type 2, which, in addition to the main hypoglycemic actions, showed positive effects on the cardiovascular system, kidneys, as well as lowering UA.

scholarly journals Mitigation of the Adverse Consequences of Nutrient Excess on the Kidney: A Unified Hypothesis to Explain the Renoprotective Effects of Sodium-Glucose Cotransporter 2 Inhibitors

2020 ◽  
Vol 51 (4) ◽  
pp. 289-293 ◽  
Author(s):  
Milton Packer
Keyword(s):  
Type 2 Diabetes ◽  
Adipose Tissue ◽  
Renin Angiotensin System ◽  
Tissue Expansion ◽  
Adenosine Monophosphate ◽  
Sglt2 Inhibitors ◽  
Sirtuin 1 ◽  
Glomerular Hyperfiltration ◽  
Sodium Glucose Cotransporter

The 2 most common causes of chronic kidney disease worldwide (type 2 diabetes and obesity) are states of nutrient excess, suggesting that fuel overabundance leads to deleterious effects on the structure and function of the kidneys. Three pathophysiological pathways may potentially explain this linkage. First, both obesity and type 2 diabetes are characterized by glomerular hyperfiltration, which may result from increased proximal tubular reabsorption of sodium (due to enhanced glucose and sodium transport) coupled with activation of the renin-angiotensin system. Second, both obesity and type 2 diabetes are characterized by adipose tissue expansion and inflammation, followed by the augmented synthesis and release of lipid intermediates and proinflammatory adipocytokines that can have deleterious effects on the kidney. Third, states of nutrient excess cause a diminution in the activation of the energy sensors, sirtuin-1 (SIRT1) and adenosine monophosphate-activated protein kinase (AMPK). The result is a suppression of autophagy, a lysosomal degradative pathway that is responsible for the clearance of damaged organelles that are an important source of oxidative and endoplasmic reticulum stress and inflammation. Sodium-glucose cotransporter 2 (SGLT2) inhibitors induces a transcriptional paradigm that mimics fasting, which leads to the amelioration of glomerular hyperfiltration and adipose tissue inflammation as well as augmentation of AMPK/SIRT1 signaling and autophagy, thereby acting to mute organellar and cellular stress in the kidney. Therefore, SGLT2 inhibitors are positioned to antagonize all 3 pathways by which nutrient excess can lead to nephropathy.

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