Investigators have hypothesized that sodium-glucose cotransporter 2 (SGLT2) inhibitors exert diuretic effects that contribute to their ability to reduce serious heart failure events, and this action ...is particularly important in patients with fluid retention.
This study sought to evaluate the effects of the SGLT2 inhibitor empagliflozin on symptoms, health status, and major heart failure outcomes in patients with and without recent volume overload.
This double-blind randomized trial compared the effects of empagliflozin and placebo in 3,730 patients with heart failure and a reduced ejection fraction, with or without diabetes. Approximately 40% of the patients had volume overload in the 4 weeks before study enrollment.
Patients with recent volume overload were more likely to have been hospitalized for heart failure and to have received an intravenous diuretic agent in an outpatient setting in the previous 12 months, and to experience a heart failure event following randomization, even though they were more likely to be treated with high doses of a loop diuretic agent as an outpatient (all p < 0.001). When compared with placebo, empagliflozin reduced the composite risk of cardiovascular death or hospitalization for heart failure, decreased total hospitalizations for heart failure, and improved health status and functional class. Yet despite the predisposition of patients with recent volume overload to fluid retention, the magnitude of these benefits (even after 1 month of treatment) was not more marked in patients with recent volume overload (interaction p values > 0.05). Changes in body weight, hematocrit, and natriuretic peptides (each potentially indicative of a diuretic action of SGLT2 inhibitors) did not track each other closely in their time course or in individual patients.
Taken together, study findings do not support a dominant role of diuresis in mediating the physiological changes or clinical benefits of SGLT2 inhibitors on the course of heart failure in patients with a reduced ejection fraction. (EMPagliflozin outcomE tRial in Patients With chrOnic heaRt Failure With Reduced Ejection Fraction EMPEROR-Reduced; NCT03057977).
A kettes típusú nátrium-glükóz-transzporter (SGLT2) inhibitorok hatásos antidiabetikus terápiának bizonyultak kettes típusú diabetes mellitusban (T2DM) és a javuló glikémiás kontroll mellett testsúly ...és vérnyomáscsökkentő hatással is rendelkeznek. Az SGLT2-inhibitorok nagy, multicentrikus randomizált vizsgálatokban az ejekcós frakció teljes spektrumán a diabéteszes státusztól függetlenül javították a kardiovaszkuláris és renális kimenetelt. Ezen előnyös hatások hátterében álló mechanizmusok jelenleg is intenzív kutatás tárgyát képezik, mivel minden bizonnyal túlmutatnak a javuló glikémiás kontrollon. A korai natriuresis, a plazmatérfogat csökkenése, a vaszkuláris funkció javulása, a vérnyomás csökkenése és a szöveti nátriumszint változása mind közrejátszhatnak ezen hatások kialakulásában. Az SGLT2-inhibitorok további előnyös mechanizmusai közé tartoznak a zsírszövet által közvetített gyulladás csökkenése, a ketontestek, mint energiaforrás felé történő elmozdulás, az oxidatív stressz és a szérum húgysavszintjének csökkenése, illetve a csökkent glomeruláris hiperfiltráció. További, megtartott ejekciós frakcióval és nem diabéteszes vesebetegekkel végzett vizsgálatok még több információt adhatnak majd az SGLT2-gátlók pontos hatásmechanizmusáról.
The synthesis of ketone as a synthetic intermediate of canagliflozin from a gluconolactone‐derived thioester and a Grignard reagent with the aid of copper is likened to making Taiyaki, a Japanese ...fish‐shaped waffle with sweet red bean inside. The thioester (sweet red beans) and the Grignard reagent (waffle batter) are baked on a copper waffle iron to get the desired ketone as Taiyaki. More information can be found in the Research Article by H. Tsurugi, M. Seki, K. Mashima, and co‐workers (DOI: 10.1002/chem.202200474).
Background: Sodium-Glucose Co-Transporter-2 Inhibitors (SGLT2-IS) have been shown to increase hemoglobin (Hb) levels, hematocrit, and erythrocyte count. It has also been found that these agents can ...potentially reduce the risk of anemia and minimize the need for erythropoiesis stimulating agents (ESA) and other treatments in patients with type 2 diabetes (T2D) and chronic kidney disease (CKD). However the precise mechanism for such an effect is still conflicting. Aim: We aimed at providing an overview of the effects of SGLT2-IS on hematological parameters, specifically focusing on their potential to improve anemia and erythropoiesis in patients with diabetes mellitus (DM). Additionally the proposed mechanisms by which SGLT2-IS may improve Hb levels besides their clinical importance and future directions will also be highlighted. Results: Based on the obtained data from latest literatures, SGLT2-IS may improve the status of anemia and other linked abnormalities via their mild diuretic potential, effects on erythropoietin (EPO) production, and possible increase in renal oxygen delivery. Conclusion: SGLT2-IS may have a promising role in improving multiple aspects of blood, circulatory and renal systems health in patients with DM, beyond their primary glucose-lowering role.
BACKGROUND:SGLT2 (sodium-glucose cotransporter 2) inhibitors lower cardiovascular events in type 2 diabetes mellitus but whether they promote direct cardiac effects remains unknown. We sought to ...determine if empagliflozin causes a decrease in left ventricular (LV) mass in people with type 2 diabetes mellitus and coronary artery disease.
METHODS:Between November 2016 and April 2018, we recruited 97 individuals ≥40 and ≤80 years old with glycated hemoglobin 6.5% to 10.0%, known coronary artery disease, and estimated glomerular filtration rate ≥60mL/min/1.73m. The participants were randomized to empagliflozin (10 mg/day, n=49) or placebo (n=48) for 6 months, in addition to standard of care. The primary outcome was the 6-month change in LV mass indexed to body surface area from baseline as measured by cardiac magnetic resonance imaging. Other measures included 6-month changes in LV end-diastolic and -systolic volumes indexed to body surface area, ejection fraction, 24-hour ambulatory blood pressure, hematocrit, and NT-proBNP (N-terminal pro b-type natriuretic peptide).
RESULTS:Among the 97 participants (90 men 93%, mean standard deviation age 62.8 9.0 years, type 2 diabetes mellitus duration 11.0 8.2 years, estimated glomerular filtration rate 88.4 16.9 mL/min/1.73m, LV mass indexed to body surface area 60.7 11.9 g/m), 90 had evaluable imaging at follow-up. Mean LV mass indexed to body surface area regression over 6 months was 2.6 g/m and 0.01 g/m for those assigned empagliflozin and placebo, respectively (adjusted difference −3.35 g/m; 95% CI, −5.9 to −0.81g/m, P=0.01). In the empagliflozin-allocated group, there was significant lowering of overall ambulatory systolic blood pressure (adjusted difference −6.8mmHg, 95% CI −11.2 to −2.3mmHg, P=0.003), diastolic blood pressure (adjusted difference −3.2mmHg; 95% CI, −5.8 to −0.6mmHg, P=0.02) and elevation of hematocrit (P=0.0003).
CONCLUSIONS:Among people with type 2 diabetes mellitus and coronary artery disease, SGLT2 inhibition with empagliflozin was associated with significant reduction in LV mass indexed to body surface area after 6 months, which may account in part for the beneficial cardiovascular outcomes observed in the EMPA-REG OUTCOME (BI 10773 Empagliflozin Cardiovascular Outcome Event Trial in Type 2 Diabetes Mellitus Patients) trial.
CLINICAL TRIAL REGISTRATION:URLhttps://www.clinicaltrials.gov. Unique identifierNCT02998970.
Background: The cost-effectiveness of sodium-glucose cotransporter 2 (SGLT2) inhibitors for chronic kidney disease (CKD) has not been evaluated in Japan, so we analyzed the cost-effectiveness of ...dapagliflozin, an SGLT2 inhibitor, for CKD stages 3a and 3b.Methods and Results: We used the Markov model for CKD to assess the costs and benefits associated with and without dapagliflozin from a health system perspective. We estimated the incremental cost-effectiveness ratio (ICER), expressed as per quality-adjusted life-years (QALYs). An ICER <5 million Japanese yen (JPY)/QALY was judged to be cost-effective. The effect of dapagliflozin on renal and cardiovascular events was based on published clinical trials. In patients with CKD stage 3a, the ICER of dapagliflozin over standard treatment was 4.03 million JPY/QALY gained. With a cost-effectiveness threshold of 5 million JPY/QALY gained, the cost-effectiveness probability of dapagliflozin over standard treatment was 52.6%. In patients with CKD stage 3b, the ICER of dapagliflozin over standard treatment was 0.12 million JPY/QALY gained. The cost-effectiveness probability of dapagliflozin over standard treatment was 75.2%.Conclusions: The results seemed to show acceptable cost-effectiveness when dapagliflozin was used for CKD stage 3b. On the other hand, cost-effectiveness of dapagliflozin for CKD stage 3a was ambiguous, and further validation is needed.
Heart failure (HF), which has a high morbidity and mortality rate, is nevertheless a common and crippling ailment, especially in older populations. The complicated pathophysiology of heart failure ...(HF), which includes oxidative stress, endothelial dysfunction, fibrosis, and inflammation, is frequently not sufficiently treated despite advances in medication. Inhibitors of the sodium-glucose co-transporter 2 (SGLT2) have become a key treatment for HF in patients with varying left ventricular ejection fractions (LVEF). SGLT2 inhibitors have been shown in recent clinical trials to considerably lower hospitalization rates for heart failure, cardiovascular mortality, and all-cause mortality. The mechanisms of SGLT2 inhibitors, such as better ventricular loading, increased heart metabolic efficiency, and decreased inflammation and necrosis, are covered in this review. Additionally, we provide an overview of four important clinical trials—DAPA-HF, EMPEROR-Reduced, EMPEROR-Preserved, and DELIVER—highlighting their effectiveness in lowering unfavourable cardiovascular outcomes for patients with heart failure who have preserved (HFpEF), slightly reduced (HFmrEF), or reduced (HFrEF). The results validate the need for SGLT2 inhibitors in all-inclusive HF treatment plans by highlighting their adaptability and safety in a range of clinical contexts.
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