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.

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 Effects of Canagliflozin on Heart Failure Outcomes Associated With Preserved and Reduced Ejection Fraction in Type 2 Diabetes Mellitus

Circulation ◽  
2019 ◽  
Vol 139 (22) ◽  
pp. 2591-2593 ◽  
Author(s):  
Gemma A. Figtree ◽  
Karin Rådholm ◽  
Terrance D. Barrett ◽  
Vlado Perkovic ◽  
Kenneth W. Mahaffey ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Heart Failure ◽  
Type 2 Diabetes ◽  
Type 2 Diabetes Mellitus ◽  
Ejection Fraction ◽  
Reduced Ejection Fraction

scholarly journals Association between Markers of Fibrosis and Heart Failure Incidence in Patients with Type 2 Diabetes Mellitus

2021 ◽  
Vol 2021 ◽  
pp. 1-8
Author(s):  
Denis A. Lebedev ◽  
Elena A. Lyasnikova ◽  
Elena Yu. Vasilyeva ◽  
Nikolai P. Likhonosov ◽  
Maria Yu. Sitnikova ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Heart Failure ◽  
Type 2 Diabetes ◽  
Type 2 Diabetes Mellitus ◽  
Type I ◽  
Procollagen Type ◽  
Sodium Glucose Cotransporter ◽  
Increased Risk

Type 2 diabetes mellitus (T2DM) and chronic heart failure (HF) have close association, and several biomarkers have been studied to better understand this association and improve prediction of HF in T2DM. Furthermore, in recent clinical trials, sodium glucose cotransporter 2 inhibitors (SGLT2i), glucose-lowering drugs, improved HF outcomes. The objective of the present study was to evaluate association between circulating biomarkers of fibrosis and incidence of HF with preserved ejection fraction (HFpEF) in patients with T2DM receiving sodium glucose cotransporter 2 inhibitors (SGLT2i). Materials and Methods. At baseline, transthoracic echocardiography and laboratory assessment of N-terminal fragment of the brain natriuretic peptide (Nt-proBNP), soluble suppression of tumorigenesis-2 (sST2), galectin-3 (Gal-3), C-terminal propeptide of procollagen type I (PICP), N-terminal propeptide of procollagen type III (PIIINP), matrix metalloproteinase-9 (MMP-9), and tissue inhibitor of matrix proteinase-1 (TIMP-1) were done. After 3 years of follow-up, information about HF events (hospitalization for HF, established HF in outpatient department by a cardiologist) was obtained. Results. Seventy-two patients were included in the study. The mean age was 57 (49.7; 63.2) years; 44% were female. Most patients had T2DM for more than 4 years. All patients were overweight or had obesity, and 93% patients had arterial hypertension (AH). After 3 years of follow-up, HFpEF was established in 21% patients. Patients were divided into two groups according to the presence of HFpEF, and baseline characteristics were compared. Patients with HF were older and had longer diabetes and AH duration and higher Nt-proBNP, Gal-3, PIIINP, and PICP levels at baseline than patients without HF (all p < 0.05 ). Gal − 3 > 10  ng/ml ( OR = 2.25 ; 95% CI, 1.88–5.66; p = 0.01 ) and NT − pro − BNP > 80  pg/ml ( OR = 2.64 ; 95% CI, 1.56–4.44; p = 0.001 ) were associated with increased risk of HF incidence. Age > 60 years, diabetes duration > 10 years, and presence of abdominal obesity were independent predictors of HFpEF as well. Conclusions. T2DM patients treated with SLGT2i, who developed HFpEF after 3 years of follow-up, had higher PICP, PIIINP, Gal-3, and NT-proBNP serum concentrations at baseline, and Gal-3 level was an independent predictor of HFpEF.

scholarly journals Patients characteristics and prognostic implications of type 2 diabetes mellitus in heart failure with preserved, mid-rang reduced and reduced ejection fraction

2021 ◽  
Vol 72 (1) ◽  
pp. 18-24
Author(s):  
Marija Mrvošević ◽  
Marija Polovina
Keyword(s):  
Diabetes Mellitus ◽  
Heart Failure ◽  
Type 2 Diabetes ◽  
Type 2 Diabetes Mellitus ◽  
Ejection Fraction ◽  
Reduced Ejection Fraction ◽  
One Year ◽  
Unique Predictor ◽  
The Impact

Introduction: Type 2 diabetes mellitus (T2DM) is frequent in patients with heart failure (HF) and correlated with an increased morbidity and mortality. The features and outcomes of patients with and without T2DM, depending on the HF type (HF with preserved: HFpEF, mid-range: HFmrEF; and reduced ejection fraction: HFrEF), are inefficiently explored. Aim: To explore the impact of T2DM on clinical features and one-year overall mortality in patients with HFrEF, HFmrEF and HFpEF. Material and methods: A prospective, observational study was conducted, including patients with HF at the Department of Cardiology, Clinical Center of Serbia, Belgrade. The enrolment occurred between November 2018 and January 2019. The study outcome was one-year all-cause mortality. Results: Study included 242 patients (mean-age, 71 ± 13 years, men 57%). T2DM was present in 31% of patients. The proportion of T2DM was similar amid patients with HFrEF, HFmrEF, and HFpEF. Regardless of the HF type, patients with T2DM were probably older and had a higher prevalence of myocardial infarction, other types of coronary disorder or peripheral arterial disorder (all p < 0.001). Also, chronic kidney disease was more prevalent in T2DM (p < 0.001). In HFpEF, T2DM patients were commonly female, and usually had hypertension and atrial fibrillation (all p < 0.001). Estimated one-year total mortality rates were significantly higher in T2DM patients. It also emerged as a unique predictor of higher mortality in HFrEF (HR; 1.33; 95% CI; 1.34 - 2.00), HFmrEF (HR; 1.13; 95% CI; 1.0 - 1.24) and HFpEF (HR; 1.21; 95% CI; 1.09 - 1.56), all p < 0.05. Conclusion: Compared with non-diabetics, patients with HF and T2DM are older, with higher prevalence of comorbidities and greater one-year mortality, regardless of HF type. Heart failure is a unique predictor of mortality in all HF types in multivariate analysis. Considering the increased risk, T2DM requires meticulous screening/diagnosis and contemporary treatment to improve outcomes.

scholarly journals Modification of the of the cardiometabolic profile using combined therapy of the angiotensin receptor-neprilysin inhibitor and empagliflozin in comorbid patients with Chronic Heart Failure and type 2 Diabetes Mellitus

Kardiologiia ◽  
2020 ◽  
Vol 60 (5) ◽  
pp. 146-152
Author(s):  
O. V. Tsygankova ◽  
V. V. Veretyuk ◽  
V. Yu. Mareev
Keyword(s):  
Diabetes Mellitus ◽  
Heart Failure ◽  
Type 2 Diabetes ◽  
Type 2 Diabetes Mellitus ◽  
Chronic Heart Failure ◽  
Ejection Fraction ◽  
Angiotensin Receptor ◽  
Neprilysin Inhibitor ◽  
Angiotensin Receptor Neprilysin Inhibitor

Chronic heart failure (CHF) and type 2 diabetes mellitus (DM2) and very common comorbidities with bidirectional, mutually aggravating courses. DM2 is known as an independent risk factor of cardiovascular complications whereas a higher CHF functional class is associated with increased risk of DM2. At present time, hypoglycemic drugs of the gliflozin class and the angiotensin receptor-neprilysin inhibitor (ARNI) are widely discussed in connection with their use in the treatment of patients with CHF and DM. The PARADIGM-HF study investigated effects of long-term treatment of CHF with reduced ejection fraction with presently the only representative of the ARNI class, a single supramolecular complex of valsartan-sacubitril. This medicine has already exceled enalapril at the effect not only on the incidence of nonfatal and fatal cardiovascular events but also on general mortality. Mean age of patients included into that study was 63.8±11.5 years; 21 % of them were females. In real-life clinical practice, physicians more frequently see older patients, and most of them are females, particularly with DM2. On the other hand, sodium-glucose cotransporter-2 inhibitors, including empagliflozin, significantly decreased the death rate and the frequency of CHF exacerbations in patients with DM2 and concomitant cardiovascular diseases, including CHF. This article describes a clinical case of initiating the valsartan-sacubitril treatment in combination with empagliflozin in an elderly female patient with congestive CHF with intermediate ejection fraction (EF) and comorbidities, including a history of myocardial infarction and DM2. Of interest is the rapid positive dynamics of clinical, laboratory (NT-proBNP) and instrumental (echocardiography) markers of CHF. At 3 months, the EF “recovered” from intermediate to preserved during the use of a comprehensive cardio-reno-metabolic approach. Both cardiologists and endocrinologists should definitely consider this approach in managing such patients since current cardiological drugs have additional pleiotropic metabolic effects whereas hypoglycemic drugs, in their turn, influence the cardiological prognosis.

Sign in / Sign up

Export Citation Format

Share Document