Sodium glucose co-transporter type 2 inhibitors (SGLT-2 inhibitors) are a class of antidiabetics, recently approved for the treatment of patients with T2DM. They feature cardioprotective and renoprotective action, while they exert beneficial effects on metabolic parameters. Non-alcoholic fatty liver disease (NAFLD) is a frequent co-morbidity in diabetic patients. Its prevalence reaches up to 70%. Since there is no specific treatment approved for NAFLD, both experimental and clinical studies have been recently conducted highlighting the efficacy and safety of SGLT-2 inhibitors mainly in animal models and secondarily in patients with T2DM and NAFLD. This class of antidiabetics seems very attractive, improving both glycemic control and liver function tests, while inhibiting NAFLD progression. However, further investigation is required to establish them as a first-line treatment option in T2DM patients with NAFLD, after thorough assessment of their efficacy and safety in clinical practice.

• Klíčová slova
• NAFLD, SGLT-2 inhibitor, T2DM,
• MeSH
• diabetes mellitus 2. typu komplikace   farmakoterapie   metabolismus   MeSH
• glifloziny * MeSH
• glukosa metabolismus   MeSH
• hypoglykemika farmakologie   MeSH
• jaterní testy metody   MeSH
• lidé MeSH
• nealkoholová steatóza jater komplikace   farmakoterapie   metabolismus   MeSH
• transportér 2 pro sodík a glukózu MeSH
• výsledek terapie MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• zvířata MeSH
• Publikační typ
• dopisy MeSH
• Názvy látek
• glifloziny * MeSH
• glukosa MeSH
• hypoglykemika MeSH
• SLC5A2 protein, human MeSH Prohlížeč
• transportér 2 pro sodík a glukózu MeSH

Heart failure is highly prevalent in the population and, from a long-term point of view, a disease that is still difficult to treat. Although a number of medicinal solutions are offered in its treatment, there are still large reserves. The drug portfolio has recently been expanded to include the use of SGLT-2 inhibitors, initially for failure with reduced and now also with preserved ejection fraction. The question of the possibility of using these substances is discussed in the text, focusing on a possible explanation of their therapeutic benefit.

• Klíčová slova
• Ejection fraction, SGLT-2, SGLT2, clinical studies, empagliflozin, gliflozins, heart failure,
• MeSH
• diabetes mellitus 2. typu * farmakoterapie   MeSH
• funkce levé komory srdeční MeSH
• glifloziny * terapeutické užití   farmakologie   MeSH
• lidé MeSH
• srdeční selhání * farmakoterapie   MeSH
• tepový objem MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• glifloziny * MeSH

Cardiovascular diseases are still the most common cause of mortality in patients with type 2 diabetes. Studies on the cardiovascular safety of new antidiabetic treatments, that have significantly expanded the treatment options for type 2 diabetes over the last 20 years, have provided evidence not only for the cardiovascular safety of SGLT-2 inhibitors (SGLT-2i, gliflozins), but also unexpectedly showed a significant effect on the reduction of cardiovascular risk, incidence and progress of heart failure and nephroprotectivity. For the first time, a reduction in cardiovascular and overall mortality was demonstrated for empagliflozin in 2015 in patients at very high cardiovascular risk. Further studies with gliflozins in patients with diabetes, but also in non-diabetic individuals, show that gliflozins have more pharmacological similarities than differences, especially in terms of protection against the development and progression of heart failure and maintenance of glomerular filtration rate. The revolutionary contribution of SGLT-2i is therefore perceived today not only by diabetologists, but also by cardiologists and nephrologists. In ESC guidelines, SGLT-2i are recommended as a first-line antidiabetic treatment for patients with diabetes at high cardiovascular risk, attacking the hitherto unshakable position of metformin at this pole position, and their indications should be considered in patients with type 2 diabetes with atherosclerosis, heart and renal failure regardless of the level of diabetes control (values of HbA1c). In the treatment of heart failure with reduced ejection fraction (with or without diabetes), dapagliflozin and empagliflozin have been recommended by cardiologists since 2021 to prevent hospitalizations for heart failure and to reduce mortality with the strongest class and level of evidence.

• Klíčová slova
• FGF23, SGLT2, SGLT2 inhibitors, cardiovascular risk, chronic kidney disease, clinical studies, dyslipidemia, heart failure, type 2 diabetes, type 2 diabetes,
• MeSH
• benzhydrylové sloučeniny MeSH
• diabetes mellitus 2. typu * komplikace   farmakoterapie   MeSH
• glifloziny * terapeutické užití   MeSH
• glukosidy MeSH
• glykovaný hemoglobin MeSH
• hypoglykemika terapeutické užití   MeSH
• lidé MeSH
• metformin * terapeutické užití   MeSH
• srdeční selhání * farmakoterapie   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• benzhydrylové sloučeniny MeSH
• empagliflozin MeSH Prohlížeč
• glifloziny * MeSH
• glukosidy MeSH
• glykovaný hemoglobin MeSH
• hypoglykemika MeSH
• metformin * MeSH

Cardiovascular disease is still the most common cause of mortality in patients with type 2 diabetes. Some prospective studies have produced unexpected results in connection with the requirements for the demonstration of cardiovascular safety of new antidiabetics, which have significantly expanded the treatment options for diabetes over the past 20 years. Although these studies were statistically designed to exclude excessive cardiovascular risk in patients with type 2 diabetes, some drugs have shown not only cardiovascular safety but also significant cardioprotective and nephroprotective effects in these studies. For the first time, a reduction in cardiovascular and overall mortality was demonstrated for the SGLT2 inhibitor empagliflozin in EMPA-REG OUTCOME trial in patients at very high cardiovascular risk. We already know that a beneficial effect on the risk of heart failure, but also renal failure, is a class effect in gliflozins. The revolutionary benefits of SGLT2 inhibitors are now perceived not only by diabetologists, but also by cardiologists and nephrologists. In European Society of Cardiology clinical guidelines, gliflozins even endanger the still unshakable position of metformin as the first line of antidiabetic therapy in patients with very high cardiovascular risk. Their indication should be today considered in all patients with type 2 diabetes and atherosclerosis, cardiac and renal failure regardless of diabetes control because they can reduce cardiovascular risk, risk of hospitalizations for heart failure and preserve glomerular filtration rate.

• Klíčová slova
• SGLT2 inhibitors, Type 2 diabetes, cardiovascular risk, chronic kidney disease, glucuretics, heart failure,
• MeSH
• benzhydrylové sloučeniny MeSH
• diabetes mellitus 2. typu * komplikace   farmakoterapie   MeSH
• glifloziny * terapeutické užití   MeSH
• hypoglykemika terapeutické užití   MeSH
• kardiovaskulární nemoci * prevence a kontrola   MeSH
• lidé MeSH
• metformin * MeSH
• prospektivní studie MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• benzhydrylové sloučeniny MeSH
• glifloziny * MeSH
• hypoglykemika MeSH
• metformin * MeSH

(1) Background: empagliflozin, sodium-glucose co-transporter 2 (SGLT-2) inhibitor, is an effective antidiabetic agent with strong cardio- and nephroprotective properties. The mechanisms behind its cardio- and nephroprotection are still not fully clarified. (2) Methods: we used male hereditary hypertriglyceridemic (hHTG) rats, a non-obese model of dyslipidaemia, insulin resistance, and endothelial dysfunction fed standard diet with or without empagliflozin for six weeks to explore the molecular mechanisms of empagliflozin effects. Nuclear magnetic resonance (NMR)-based metabolomics; quantitative PCR of relevant genes involved in lipid and glucose metabolism, or senescence; glucose and palmitic acid oxidation in isolated tissues and cell lines of adipocytes and hepatocytes were used. (3) Results: empagliflozin inhibited weight gain and decreased adipose tissue weight, fasting blood glucose, and triglycerides and increased HDL-cholesterol. It also improved insulin sensitivity in white fat. NMR spectroscopy identified higher plasma concentrations of ketone bodies, ketogenic amino acid leucine and decreased levels of pyruvate and alanine. In the liver, adipose tissue and kidney, empagliflozin up-regulated expression of genes involved in gluconeogenesis and down-regulated expression of genes involved in lipogenesis along with reduction of markers of inflammation, oxidative stress and cell senescence. (4) Conclusion: multiple positive effects of empagliflozin, including reduced cell senescence and oxidative stress, could contribute to its long-term cardio- and nephroprotective actions.

• Klíčová slova
• cell senescence, empagliflozin, hereditary hypertriglyceridemic rat model, hypertriglyceridemia, insulin sensitivity, metabolic syndrome,
• MeSH
• aplikace orální MeSH
• benzhydrylové sloučeniny aplikace a dávkování   MeSH
• buňky 3T3-L1 MeSH
• buňky Hep G2 MeSH
• down regulace účinky léků   MeSH
• dyslipidemie farmakoterapie   MeSH
• glifloziny aplikace a dávkování   MeSH
• glukoneogeneze účinky léků   genetika   MeSH
• glukosidy aplikace a dávkování   MeSH
• hmotnostní přírůstek účinky léků   MeSH
• hypertriglyceridemie farmakoterapie   metabolismus   MeSH
• hypoglykemika aplikace a dávkování   MeSH
• inzulinová rezistence MeSH
• játra metabolismus   MeSH
• krysa rodu Rattus MeSH
• ledviny metabolismus   MeSH
• lidé MeSH
• lipogeneze účinky léků   genetika   MeSH
• modely nemocí na zvířatech MeSH
• myši MeSH
• oxidační stres účinky léků   MeSH
• stárnutí buněk účinky léků   MeSH
• tuková tkáň metabolismus   MeSH
• upregulace účinky léků   MeSH
• viabilita buněk účinky léků   MeSH
• výsledek terapie MeSH
• zvířata MeSH
• Check Tag
• krysa rodu Rattus MeSH
• lidé MeSH
• mužské pohlaví MeSH
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• benzhydrylové sloučeniny MeSH
• empagliflozin MeSH Prohlížeč
• glifloziny MeSH
• glukosidy MeSH
• hypoglykemika MeSH

A new class of antidiabetic drugs - gliflozins (inhibitors of sodium glucose cotransporter-2; SGLT-2i) stimulate glucose and sodium excretion, thereby contributing to improved glycemic control, weight loss and blood pressure reduction in diabetic patients. Large clinical trials in patients with type 2 diabetes treated with empagliflozin, canagliflozin or dapagliflozin have demonstrated their excellent efficacy in improving many cardiovascular outcomes, including the reduction of death from cardiovascular diseases, non-fatal myocardial infarction or stroke, and hospitalization for heart failure. Moreover, the beneficial effects of SGLT-2i were also demonstrated in the decrease in proteinuria, which leads to a lower risk of progression to end-stage renal disease and thus a delay in initiation of the renal replacement therapy. Unexpectedly, their cardioprotective and renoprotective effects have been demonstrated not only in patients with diabetes but also in those without diabetes. Recently, much effort has been focused on patients with heart failure (either with reduced or preserved ejection fraction) or liver disease. Experimental studies have highlighted pleiotropic effects of SGLT-2 inhibitors beyond their natriuretic and glycosuric effects, including reduction of fibrosis, inflammation, reactive oxygen species, and others. Our results in experimental non-diabetic models of hypertension, chronic kidney disease and heart failure are partially consistent with these findings. This raises the question of whether the same mechanisms are at work in diabetic and non-diabetic conditions, and which mechanisms are responsible for the beneficial effects of gliflozins under non-diabetic conditions. Are these effects cardio-renal, metabolic, or others? This review will focus on the effects of gliflozins under different pathophysiological conditions, namely in hypertension, chronic kidney disease, and heart failure, which have been evaluated in non-diabetic rat models of these diseases. Key words: SGLT-2 inhibitor, hypertension, chronic kidney disease, heart failure, liver disease, rat.

• Klíčová slova
• SGLT-2 inhibitor, Hypertension, Chronic kidney disease, Heart failure, Liver disease, Rat,
• MeSH
• glifloziny * terapeutické užití   farmakologie   MeSH
• hypoglykemika terapeutické užití   farmakologie   MeSH
• kardiovaskulární nemoci * farmakoterapie   prevence a kontrola   MeSH
• lidé MeSH
• modely nemocí na zvířatech MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH
• Názvy látek
• glifloziny * MeSH
• hypoglykemika MeSH

Sodium glucose transporter type 2 (SGLT2) molecules are found in proximal tubules of the kidney, and perhaps in the brain or intestine, but rarely in any other tissue. However, their inhibitors, intended to improve diabetes compensation, have many more beneficial effects. They improve kidney and cardiovascular outcomes and decrease mortality. These benefits are not limited to diabetics but were also found in non-diabetic individuals. The pathophysiological pathways underlying the treatment success have been investigated in both clinical and experimental studies. There have been numerous excellent reviews, but these were mostly restricted to limited aspects of the knowledge. The aim of this review is to summarize the known experimental and clinical evidence of SGLT2 inhibitors' effects on individual organs (kidney, heart, liver, etc.), as well as the systemic changes that lead to an improvement in clinical outcomes.

• Klíčová slova
• SGLT2, SGLT2 inhibitors, chronic kidney disease, diabetes, heart failure,
• MeSH
• diabetes mellitus 2. typu * farmakoterapie   metabolismus   MeSH
• glifloziny * farmakologie   terapeutické užití   MeSH
• glukosa terapeutické užití   MeSH
• kardiovaskulární systém * metabolismus   MeSH
• lidé MeSH
• sodík metabolismus   MeSH
• transportér 2 pro sodík a glukózu metabolismus   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH
• Názvy látek
• glifloziny * MeSH
• glukosa MeSH
• sodík MeSH
• transportér 2 pro sodík a glukózu MeSH

The sodium-glucose cotransporter 2 inhibitor empagliflozin reduces the risk of cardiovascular death or heart failure hospitalization in patients with chronic heart failure, but whether empagliflozin also improves clinical outcomes when initiated in patients who are hospitalized for acute heart failure is unknown. In this double-blind trial (EMPULSE; NCT04157751 ), 530 patients with a primary diagnosis of acute de novo or decompensated chronic heart failure regardless of left ventricular ejection fraction were randomly assigned to receive empagliflozin 10 mg once daily or placebo. Patients were randomized in-hospital when clinically stable (median time from hospital admission to randomization, 3 days) and were treated for up to 90 days. The primary outcome of the trial was clinical benefit, defined as a hierarchical composite of death from any cause, number of heart failure events and time to first heart failure event, or a 5 point or greater difference in change from baseline in the Kansas City Cardiomyopathy Questionnaire Total Symptom Score at 90 days, as assessed using a win ratio. More patients treated with empagliflozin had clinical benefit compared with placebo (stratified win ratio, 1.36; 95% confidence interval, 1.09-1.68; P = 0.0054), meeting the primary endpoint. Clinical benefit was observed for both acute de novo and decompensated chronic heart failure and was observed regardless of ejection fraction or the presence or absence of diabetes. Empagliflozin was well tolerated; serious adverse events were reported in 32.3% and 43.6% of the empagliflozin- and placebo-treated patients, respectively. These findings indicate that initiation of empagliflozin in patients hospitalized for acute heart failure is well tolerated and results in significant clinical benefit in the 90 days after starting treatment.

• MeSH
• benzhydrylové sloučeniny škodlivé účinky   MeSH
• diabetes mellitus 2. typu * farmakoterapie   MeSH
• dvojitá slepá metoda MeSH
• funkce levé komory srdeční MeSH
• glifloziny * škodlivé účinky   MeSH
• glukosidy MeSH
• hospitalizace MeSH
• lidé MeSH
• srdeční selhání * MeSH
• tepový objem MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• randomizované kontrolované studie MeSH
• Názvy látek
• benzhydrylové sloučeniny MeSH
• empagliflozin MeSH Prohlížeč
• glifloziny * MeSH
• glukosidy MeSH

In solid tumors, hypoxia (lack of oxygen) is developed, which leads to the development of resistance of tumor cells to chemotherapy and radiotherapy through various mechanisms. Nevertheless, hypoxic cells are particularly vulnerable when glycolysis is inhibited. For this reason, in this study, the development of magnetically targetable nanocarriers of the sodium-glucose transporter protein (SGLT2) inhibitor dapagliflozin (DAPA) was developed for the selective delivery of DAPA in tumors. This nanomedicine in combination with radiotherapy or chemotherapy should be useful for effective treatment of hypoxic tumors. The magnetic nanoparticles consisted of a magnetic iron oxide core and a poly(methacrylic acid)-graft-poly(ethyleneglycol methacrylate) (PMAA-g-PEGMA) polymeric shell. The drug (dapagliflozin) molecules were conjugated on the surface of these nanoparticles via in vivo hydrolysable ester bonds. The nanoparticles had an average size of ~ 70 nm and exhibited a DAPA loading capacity 10.75% (w/w) for a theoretical loading 21.68% (w/w). The magnetic responsiveness of the nanoparticles was confirmed with magnetophoresis experiments. The dapagliflozin-loaded magnetic nanoparticles exhibited excellent colloidal stability in aqueous and biological media. Minimal (less than 15% in 24 h) drug release from the nanoparticles occurred in physiological pH 7.4; however, drug release was significantly accelerated in pH 5.5. Drug release was also accelerated (triggered) under the influence of an alternating magnetic field. The DAPA-loaded nanoparticles exhibited higher in vitro anticancer activity (cytotoxicity) against A549 human lung cancer cells than free DAPA. The application of an external magnetic field gradient increased the uptake of nanoparticles by cells, leading to increased cytotoxicity. The results justify further in vivo studies of the suitability of DAPA-loaded magnetic nanoparticles for the treatment of hypoxic tumors.

• Klíčová slova
• cytotoxicity, dapagliflozin, drug targeting, hypoxia, magnetic nanoparticles, tumor,
• MeSH
• benzhydrylové sloučeniny aplikace a dávkování   chemie   MeSH
• buňky A549 MeSH
• glifloziny MeSH
• glukosidy aplikace a dávkování   chemie   MeSH
• lékové transportní systémy metody   MeSH
• lidé MeSH
• magnetické nanočástice aplikace a dávkování   chemie   MeSH
• nádorová hypoxie účinky léků   fyziologie   MeSH
• nádorové buněčné linie MeSH
• nanomedicína metody   MeSH
• nosiče léků aplikace a dávkování   chemie   MeSH
• transportér 2 pro sodík a glukózu MeSH
• uvolňování léčiv MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• benzhydrylové sloučeniny MeSH
• dapagliflozin MeSH Prohlížeč
• glifloziny MeSH
• glukosidy MeSH
• magnetické nanočástice MeSH
• nosiče léků MeSH
• SLC5A2 protein, human MeSH Prohlížeč
• transportér 2 pro sodík a glukózu MeSH

Empagliflozin is agent of new antidiabetic drugs that cause glycosuria blocking the glucose reuptake in the proxi-mal tubule. The loss of 50-100 g of glucose / 24 hours in the urine results in a reduction of fasting glucose, especially post-prandial glucose, the energy expenditure of 200-400 kcal / day and blood pressure lowering. Treatment efficacy does not decrease over time, as it is not dependent on its own insulin production. The work evaluates the safety of modern treatment with empagliflozin which will soon appear in the portfolio of antidiabetic agents in the Czech Republic. The conducted studies with a special focus on empagliflozin treatment have shown high efficacy, safety and good tolerability of drug. It has been described a higher incidence of genital infections with non-severe course, especially in women. The drug does not cause hypoglycaemia. In combination with sulfonylurea hypoglycaemia may occur. Empagliflozin does not cause clinically significant dehydration or hypotension in patients about 60 years of age, but some caution in empagliflozin treatment should be in elderly and fragile patients. The big convenience of empagliflozin is its clinically non-significant interactions with other drugs and simple dosage of 1 tablet / day orally. In conclusion, empagliflozin is highly effective oral antidiabetic agent with a potential of wide application in all stages of type 2 diabetes in monotherapy or combined with other medication. The treatment is associated with weight loss and blood pressure lowering. The drug is effective and safe until eGFR 45 ml / s, in lower values the treatment should be discontinued. The occurrence of side effects is rare, except increased incidence of genital infections especially in women and increased risk of hypoglycaemia when empagliflozin is combined with sulfonylurea.

• MeSH
• benzhydrylové sloučeniny terapeutické užití   MeSH
• diabetes mellitus 2. typu farmakoterapie   metabolismus   MeSH
• glukosidy terapeutické užití   MeSH
• hypoglykemie farmakoterapie   metabolismus   MeSH
• hypoglykemika terapeutické užití   MeSH
• kombinovaná farmakoterapie MeSH
• krevní glukóza MeSH
• kvalita života MeSH
• lidé středního věku MeSH
• lidé MeSH
• senioři MeSH
• transportér 2 pro sodík a glukózu metabolismus   MeSH
• výsledek terapie MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• benzhydrylové sloučeniny MeSH
• empagliflozin MeSH Prohlížeč
• glukosidy MeSH
• hypoglykemika MeSH
• krevní glukóza MeSH
• SLC5A2 protein, human MeSH Prohlížeč
• transportér 2 pro sodík a glukózu MeSH