Próba kliniczna EMPA-REG OUTCOME z zastosowaniem empagliflozyny — nowa era w terapii cukrzycy typu 2

Patients with type 2 diabetes (T2DM) have a significantly higher risk of developing cardiovascular disease (CVD). Despite enormous advances in the prevention and treatment of CVD, the impact of T2DM on CVD outcome remains high. It is well known that the risk of macrovascular diabetic complications increases with the severity of hyperglycemia. However, many effective glucose-lowering agents have been tested for their safety and efficacy in T2DM with CVD unfortunately most of these studies failed to show a significant benefit in terms of CV morbidity and mortality, despite intensive glycemic control. The trial Empagliflozin Cardiovascular Outcome Event Trial in Type 2 Diabetes Mellitus Patients Removing Excess Glucose EMPA-REG OUTCOME trial with empagliflozin was the first to demonstrate significant cardioprotective benefits in this population. The results of the EMPA-REG OUTCOME trial showed that the sodium-glucose co-transporter 2 (SGLT2) inhibitor empagliflozin was associated with a pronounced 38% reduction in cardiovascular mortality in subjects with T2DM and established cardiovascular dis­ease. These benefits were more related to a reduction in incident heart failure (HF) events rather than to ischaemic vascular endpoints. Several mechanisms have been put forward to explain these benefits, which also raise the possibility of using these drugs as therapies not only in the prevention of HF, but also for the treatment of patients with established HF regardless of the presence or absence of diabetetype 2 diabetes mellitus, cardiovascular morbidity and mortality, empagliflozin, sodium glucose cotransporter 2 inhibitors    U chorych na cukrzycę typu 2 (T2DM) ryzyko rozwoju chorób układu sercowo-naczyniowego (CVD) jest znamiennie wyższe. Mimo niezwykłego postępu w prewencji i leczeniu CVD utrzymuje się niekorzystny wpływ T2DM. Wiadomo, że ryzyko powikłań makronaczyniowych w cukrzycy zwiększa się wraz z nasileniem hiperglikemii. Badano liczne preparaty hipoglikemizujące pod względem ich bezpieczeństwa i prewencyjnej skuteczności w T2DM u osób z towarzyszącymi CVD, jednak większość prób klinicznych zawiodła pod względem wykazania znacznych korzyści w zmniejszeniu chorobowości i śmiertelności sercowo-naczyniowej, mimo intensywnej kontroli glikemii. Próba kliniczna The trial Empagliflozin Cardiovascular Outcome Event Trial in Type 2 Diabetes Mellitus Patients Removing Excess Glucose EMPA-REG OUTCOME była pierwszą, w której wykazano znamienną skuteczność prewencji sercowo-naczyniowej w przebiegu T2DM. Wyniki próby klinicznej EMPA-REG OUTCOME udowodniły, że inhibitor kotransportera sodowo-glukozowego 2 (SGLT2) — empagliflozyna znacząco, bo aż o 38%, obniża śmiertelność sercowo-naczyniową wśród chorych na T2DM obciążonych schorzeniami serca i naczyń. Korzyści te były raczej wynikiem ograniczenia częstości incydentów związanych z niewydolnością serca (HF) niż naczyniowych incydentów niedokrwiennych. Zaproponowano wiele mechanizmów, które mogłyby tłumaczyć tak znaczne korzyści, co w konsekwencji doprowadziło do wysunięcia propozycji zastosowania tego leku nie tylko w prewencji HF, ale także w terapii jawnej HF bez względu na obecność towarzyszącej cukrzycy

Beneficial In Vitro Effects of a Low <i>Myo</i>-Inositol Dose in the Regulation of Vascular Resistance and Protein Peroxidation under Inflammatory Conditions

Oxidative stress induces functional changes in arteries. Therefore, the effect of myo-inositol, a possible anti-inflammatory/antioxidant agent was studied on human plasma and rat thoracic arteries. Aortic rings from male Wistar rats (3 months of age) were incubated with myo-inositol (1, 10 and 100 μM, 120 min) and analyzed using the gas chromatography (GC) method. In another experiment, aortic rings were protected first with myo-inositol (1 µM, 60 min) and then subjected to a thromboxane receptor agonist (U-46619, 0.1 nM, 60 min). Therefore, these four groups under the following conditions were studied: (i) the control in the vehicle; (ii) myo-inositol; (iii) the vehicle plus U-46619; (iv) myo-inositol plus U-46619. The hemostatic parameters of human plasma and an H2O2/Fe2+ challenge for lipid and protein peroxidation were also performed. Myo-inositol was not absorbed into the pre-incubated aortic rings as measured by the GC method (0.040 µg/mg, p ≥ 0.8688). The effect of myo-inositol was more significant in the impaired arteries due to U-46619 incubation, which resulted in an improved response to acetylcholine (% Emax: 58.47 vs. 86.69), sodium nitroprusside (logEC50: −7.478 vs. −8.076), CORM-2 (% Emax: 44.08 vs. 83.29), pinacidil (logEC50: −6.489 vs. −6.988) and noradrenaline (logEC50: −7.264 vs. −6.525). This was most likely a possible response to increased nitric oxide release (×2.6-fold, p p = 0.0012). KCl-induced membrane depolarization was not modified (p ≥ 0.4768). Both the plasma protein carbonylation (×0.7-fold, p = 0.0006), and the level of thiol groups (×3.2-fold, p = 0.0462) were also improved, which was not significant for TBARS (×0.8-fold, p = 0.0872). The hemostatic parameters were also not modified (p ≥ 0.8171). A protective effect of myo-inositol was demonstrated against prooxidant damage to human plasma and rat thoracic arteries, suggesting a strong role of this nutraceutical agent on vasculature which may be of benefit against harmful environmental effects