scholarly journals Sodium–glucose Cotransporter 2 Inhibitors in Heart Failure: Potential Mechanisms of Action, Adverse Effects and Future Developments

2019 ◽  
Vol 14 (1) ◽  
pp. 23-32 ◽  
Author(s):  
Juan Tamargo
Keyword(s):  
Heart Failure ◽  
Glycaemic Control ◽  
Adverse Effects ◽  
Major Cardiovascular Events ◽  
Sodium Glucose Cotransporter ◽  
Urinary Glucose ◽  
Patients With Diabetes ◽  
Near Future ◽  
Glucose Excretion

Heart failure is a common complication in patients with diabetes, and people with both conditions present a worse prognosis. Sodium– glucose cotransporter 2 inhibitors (SGLT2Is) increase urinary glucose excretion, improving glycaemic control. In type 2 diabetes (T2D), some SGLT2Is reduce major cardiovascular events, heart failure hospitalisations and worsening of kidney function independent of glycaemic control. Multiple mechanisms (haemodynamic, metabolic, hormonal and direct cardiac/renal effects) have been proposed to explain these cardiorenal benefits. SGLT2Is are generally well tolerated, but can produce rare serious adverse effects, and the benefit/risk ratio differs between SGLT2Is. This article analyses the mechanisms underlying the cardiorenal benefits and adverse effects of SGLT2Is in patients with T2D and heart failure and outlines some questions to be answered in the near future.

scholarly journals Treatment of Heart Failure with Sodium-Glucose Cotransporter 2 Inhibitors and Other Anti-diabetic Drugs

2019 ◽  
Vol 5 (1) ◽  
pp. 27-30 ◽  
Author(s):  
Thomas A Zelniker ◽  
Eugene Braunwald
Keyword(s):  
Heart Failure ◽  
Type 2 Diabetes ◽  
Renal Failure ◽  
Cardiovascular Death ◽  
Cardiovascular Outcomes ◽  
Sodium Glucose Cotransporter ◽  
Increased Risk ◽  
Patients With Diabetes ◽  
Glucagon Like Peptide 1

Patients with type 2 diabetes are at increased risk of developing heart failure, cardiovascular death and renal failure. The recent results of three large sodium-glucose cotransporter 2 inhibitor cardiovascular outcomes trials have demonstrated a reduction in heart failure hospitalisation and progressive renal failure. One trial also showed a fall in cardiovascular and total death. A broad spectrum of patients with diabetes benefit from these salutary effects in cardiac and renal function and so these trials have important implications for the management of patients with type 2 diabetes. Selected glucagon-like peptide 1 receptor agonists have also been shown to reduce adverse cardiovascular outcomes.

scholarly journals Perspective of the β-blockers for the patients with diabetes and heart failure 

2020 ◽  
Vol 8 (4) ◽  
pp. 97-99
Author(s):  
Hiroshi BANDO
Keyword(s):  
Heart Failure ◽  
Adverse Outcomes ◽  
Control Group ◽  
Sodium Glucose Cotransporter ◽  
Strict Glycemic Control ◽  
Cardiovascular Assessment ◽  
Patients With Diabetes ◽  
Outcome Trial ◽  
Β Blockers

Patients with diabetes and heart failure have been increasing due to Japanese Cardiac Registry of Heart Failure in Cardiology (JCARE-CARD) study. β-blockers showed significantly suppressed cardiovascular events in the strict glycemic control group. Sodium-glucose Cotransporter-2 Inhibitors (SGLT2i) seem to be beneficial for diabetes and heart failure. Clinical efficacy of β-blockers would be suggested from three studies including Empagliflozin Cardiovascular Outcome Event Trial in Type 2 Diabetes Mellitus Patients-Removing Excess Glucose (EMPA-REG OUTCOME) trial, Canagliflozin cardioVascular Assessment Study (CANVAS) and Dapagliflozin and Prevention of Adverse Outcomes in Heart Failure (DAPA-HF) study. Further discussion will be expected with research in detail.

scholarly journals Sodium glucose cotransporter 2 inhibitors: mechanisms of action in heart failure

2020 ◽  
Author(s):  
Mieczysław Dutka ◽  
Rafał Bobiński ◽  
Izabela Ulman-Włodarz ◽  
Maciej Hajduga ◽  
Jan Bujok ◽  
...  
Keyword(s):  
Heart Failure ◽  
Glycaemic Control ◽  
Experimental Studies ◽  
Mechanisms Of Action ◽  
New Class ◽  
Current State ◽  
Sodium Glucose Cotransporter ◽  
Patients With Diabetes ◽  
Clinical Benefits ◽  
Treatment Of Diabetes

Abstract Diabetes is a key independent risk factor in the development of heart failure (HF) and a strong, adverse prognostic factor in HF patients. HF remains the primary cause of hospitalisation for diabetics and, as previous studies have shown, when HF occurs in these patients, intensive glycaemic control does not directly improve the prognosis. Recent clinical studies assessing a new class of antidiabetic drugs, sodium-glucose cotransporter 2 inhibitors (SGLT2is) showed some unexpected beneficial results. Patients treated with SGLT2is had a significant decrease in both cardiovascular (CV) and all-cause mortality and less hospitalisations due to HF compared to those given a placebo. These significant clinical benefits occurred quickly after the drugs were administered and were not solely due to improved glycaemic control. These groundbreaking clinical trials’ results have already changed clinical practice in the management of patients with diabetes at high CV risk. These trials have triggered numerous experimental studies aimed at explaining the mechanisms of action of this unique group of drugs. This article presents the current state of knowledge about the mechanisms of action of SGLT2is developed for the treatment of diabetes and which, thanks to their cardioprotective effects, may, in the future, become a treatment for patients with HF.

scholarly journals Insulin enhances renal glucose excretion: relation to insulin sensitivity and sodium-glucose cotransport

2020 ◽  
Vol 8 (1) ◽  
pp. e001178 ◽  
Author(s):  
Ele Ferrannini ◽  
Ricardo Pereira-Moreira ◽  
Marta Seghieri ◽  
Eleni Rebelos ◽  
Aglécio L Souza ◽  
...  
Keyword(s):  
Sodium Excretion ◽  
Insulin Infusion ◽  
Glucose Production ◽  
Whole Body ◽  
Glucose Disposal ◽  
Sodium Glucose Cotransporter ◽  
Urinary Glucose ◽  
Patients With Diabetes ◽  
Sglt2 Inhibition ◽  
Glucose Excretion

IntroductionInsulin regulates renal glucose production and utilization; both these fluxes are increased in type 2 diabetes (T2D). Whether insulin also controls urinary glucose excretion is not known.MethodsWe applied the pancreatic clamp technique in 12 healthy subjects and 13 T2D subjects. Each participant received a somatostatin infusion and a variable glucose infusion to achieve (within 1 hour) and maintain glycemia at 22 mmol/L for 3 hours; next, a constant insulin infusion (240 pmol/min/kg) was added for another 3 hours. Urine was collected separately in each period for glucose and creatinine determination.ResultsDuring saline, glucose excretion was lower in T2D than controls in absolute terms (0.49 (0.32) vs 0.69 (0.18) mmol/min, median (IQR), p=0.01) and as a fraction of filtered glucose (16.2 (6.4) vs 19.9 (7.5)%, p<0.001). With insulin, whole-body glucose disposal rose more in controls than T2D (183 (48) vs 101 (48) µmol/kgFFM/min, p<0.0003). Insulin stimulated absolute and fractional glucose excretion in controls (p<0.01) but not in T2D. Sodium excretion paralleled glucose excretion. In the pooled data, fractional glucose excretion was directly related to whole-body glucose disposal and to fractional sodium excretion (r=0.52 and 0.54, both p<0.01). In another group of healthy controls, empagliflozin was administered before starting the pancreatic clamp to block sodium-glucose cotransporter 2 (SGLT2). Under these conditions, insulin still enhanced both glucose and sodium excretion.ConclusionsAcute exogenous insulin infusion jointly stimulates renal glucose and sodium excretion, indicating that the effect may be mediated by SGLTs. This action is resistant in patients with diabetes, accounting for their increased retention of glucose and sodium, and is not abolished by partial SGLT2 inhibition by empagliflozin.

scholarly journals Effect of Luseogliflozin on Heart Failure With Preserved Ejection Fraction in Patients With Diabetes Mellitus

2020 ◽  
Vol 9 (16) ◽  
Author(s):  
Kentaro Ejiri ◽  
Toru Miyoshi ◽  
Hajime Kihara ◽  
Yoshiki Hata ◽  
Toshihiko Nagano ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Heart Failure ◽  
Type 2 Diabetes ◽  
Type 2 Diabetes Mellitus ◽  
Ejection Fraction ◽  
Sodium Glucose Cotransporter ◽  
Significant Difference ◽  
Patients With Diabetes ◽  
To Receive

Background Effects of sodium‐glucose cotransporter 2 inhibitors on reducing hospitalization for heart failure have been reported in randomized controlled trials, but their effects on patients with heart failure with preserved ejection fraction ( HF p EF ) are unknown. This study aimed to evaluate the drug efficacy of luseogliflozin, a sodium‐glucose cotransporter 2 inhibitor, in patients with type 2 diabetes mellitus and HF p EF . Methods and Results We performed a multicenter, open‐label, randomized, controlled trial for comparing luseogliflozin 2.5 mg once daily with voglibose 0.2 mg 3 times daily in patients with type 2 diabetes mellitus suffering from HF p EF (left ventricular ejection fraction >45% and BNP [B‐type natriuretic peptide] concentrations ≥35 pg/mL) in a 1:1 randomization fashion. The primary outcome was the difference from baseline in BNP levels after 12 weeks of treatment between the 2 drugs. A total of 173 patients with diabetes mellitus and HF p EF were included. Of these, 83 patients were assigned to receive luseogliflozin and 82 to receive voglibose. There was no significant difference in the reduction in BNP concentrations after 12 weeks from baseline between the 2 groups. The ratio of the mean BNP value at week 12 to the baseline value was 0.79 in the luseogliflozin group and 0.87 in the voglibose group (percent change, −9.0% versus −1.9%; ratio of change with luseogliflozin versus voglibose, 0.93; 95% CI, 0.78–1.10; P =0.26). Conclusion In patients with type 2 diabetes mellitus and HF p EF , there is no significant difference in the degree of reduction in BNP concentrations after 12 weeks between luseogliflozin and voglibose. Registration URL : https://www.umin.ac.jp/ctr/index.htm ; Unique identifier: UMIN 000018395.

scholarly journals Cardiometabolic Risk Reduction: A Review of Clinical Guidelines and the Role of SGLT-2 Inhibitors

2021 ◽  
Vol 70 (6 Supplement) ◽  
Author(s):  
Reid
Keyword(s):  
Diabetes Mellitus ◽  
Heart Failure ◽  
Type 2 Diabetes ◽  
Chronic Kidney Disease ◽  
Cardiometabolic Risk ◽  
Sodium Glucose Cotransporter ◽  
Patients With Diabetes ◽  
Recommended Therapy

At the end of the activity, participants will be able to: • Identify how heart failure (HF), chronic kidney disease (CKD), and type 2 diabetes mellitus (T2DM) and associated cardiovascular (CV) risks are interconnected. • Initiate guideline-recommended therapy to reduce CV risk in patients with HF, CKD, and/or T2DM. • Apply evidence for sodium-glucose cotransporter-2 inhibitors (SGLT-2 inhibitors) to clinical practice, based on recent and emerging trials. • Review evidence suggesting increased incidence and severity of COVID-19 infection in patients with diabetes.

scholarly journals Sodium-glucose cotransporter type 2 inhibitors: successful running after two hares

2021 ◽  
Vol 26 (2S) ◽  
pp. 4534
Author(s):  
N. B. Perepech ◽  
I. E. Mikhailova
Keyword(s):  
Heart Failure ◽  
Cardiovascular Events ◽  
Large Scale ◽  
Randomized Clinical Trials ◽  
Drug Action ◽  
Sglt2 Inhibitors ◽  
Reduced Ejection Fraction ◽  
Sodium Glucose Cotransporter ◽  
Patients With Diabetes

The review is devoted to the clinical efficacy of sodium-glucose cotransporter type 2 (SGLT2) inhibitors. Information on the mechanisms of drug action is given, as well as rationale for their use in the management of patients with diabetes and heart failure (HF) is provided. The results of large-scale randomized clinical trials evaluating the efficacy of SGLT2 inhibitors are discussed. We showed the beneficial effect of SGLT-2 inhibitors on the risk of cardiovascular events in patients with type 2 diabetes. In addition, an evidence of the ability of dapagliflozin and empagliflozin to improve the prognosis of patients with HF with reduced ejection fraction without diabetes are presented. The evidence and mechanisms of the nephroprotective action of SGLT2 inhibitors in patients with diabetes and HF are considered.

Adverse Effects Associated With Newer Diabetes Therapies

2016 ◽  
Vol 30 (2) ◽  
pp. 238-244 ◽  
Author(s):  
Oluwaranti F. Akiyode ◽  
Adebola A. Adesoye
Keyword(s):  
Type 2 Diabetes ◽  
Adverse Effects ◽  
Dipeptidyl Peptidase 4 ◽  
Health Care Practitioners ◽  
Sodium Glucose Cotransporter ◽  
Dipeptidyl Peptidase 4 Inhibitors ◽  
Patients With Diabetes ◽  
Glucagon Like Peptide ◽  
Glucagon Like Peptide 1

The increasing number of newer type 2 diabetes therapies has allowed providers an increased armamentarium for the optimal management of patients with diabetes. In fact, these newer agents have unique benefits in the management of type 2 diabetes. However, they are also associated with certain adverse effects. This review article aims to describe the notable adverse effects of these newer antidiabetic therapies including the glucagon-like peptide 1 receptor agonists, dipeptidyl peptidase-4 inhibitors, and the sodium-glucose cotransporter 2 inhibitors. The adverse effects reviewed herein include pancreatitis, medullary thyroid carcinoma, heart failure, gastrointestinal disturbances, renal impairment, and genitourinary infections. More clinical data are necessary to solidify the association of some of these adverse effects with the newer diabetes agents. However, it is important for health care practitioners to be well informed and prepared to properly monitor patients for these adverse effects.

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.

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