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4.
Rev Med Suisse ; 17(747): 1397-1403, 2021 Aug 25.
Artigo em Francês | MEDLINE | ID: mdl-34431632

RESUMO

The relationships between sodium-glucose cotransporter type 2 inhibitors (SGLT2is) and kidney are complex: reduction of the glucose-lowering effect with the decline of glomerular filtration rate (GFR), biphasic effects on GFR along with treatment duration, low risk of acute kidney injury, rapid reduction of albuminuria, and, most importantly in clinical practice, a remarkable nephroprotection, with a decrease of the risk of end-stage renal disease or death from renal cause. This article describes the renal outcomes in the main clinical trials and analyses the impact of treatment with SGLT2is on renal prognosis according to different patient baseline characteristics. A nephroprotection is observed whatever the severity (even if GFR < 45 ml/min/1,73 m²) and type (with or without albuminuria, with or without diabetes) of renal disease.


Assuntos
Diabetes Mellitus Tipo 2 , Nefropatias Diabéticas , Inibidores do Transportador 2 de Sódio-Glicose , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/tratamento farmacológico , Nefropatias Diabéticas/tratamento farmacológico , Nefropatias Diabéticas/prevenção & controle , Taxa de Filtração Glomerular , Humanos , Rim , Inibidores do Transportador 2 de Sódio-Glicose/uso terapêutico
5.
Int J Mol Sci ; 22(15)2021 Jul 26.
Artigo em Inglês | MEDLINE | ID: mdl-34360742

RESUMO

Sodium-glucose co-transporter 2 inhibitors (SGLT2i) are emerging as a new treatment strategy for heart failure with reduced ejection fraction (HFrEF) and-depending on the wistfully awaited results of two clinical trials (DELIVER and EMPEROR-Preserved)-may be the first drug class to improve cardiovascular outcomes in patients suffering from heart failure with preserved ejection fraction (HFpEF). Proposed mechanisms of action of this class of drugs are diverse and include metabolic and hemodynamic effects as well as effects on inflammation, neurohumoral activation, and intracellular ion homeostasis. In this review we focus on the growing body of evidence for SGLT2i-mediated effects on cardiac intracellular Na+ as an upstream mechanism. Therefore, we will first give a short overview of physiological cardiomyocyte Na+ handling and its deterioration in heart failure. On this basis we discuss the salutary effects of SGLT2i on Na+ homeostasis by influencing NHE1 activity, late INa as well as CaMKII activity. Finally, we highlight the potential relevance of these effects for systolic and diastolic dysfunction as well as arrhythmogenesis.


Assuntos
Arritmias Cardíacas/tratamento farmacológico , Cardiotônicos/uso terapêutico , Miocárdio/metabolismo , Miócitos Cardíacos/metabolismo , Inibidores do Transportador 2 de Sódio-Glicose/uso terapêutico , Transportador 2 de Glucose-Sódio/metabolismo , Animais , Arritmias Cardíacas/metabolismo , Arritmias Cardíacas/patologia , Humanos , Miocárdio/patologia , Miócitos Cardíacos/patologia
6.
Am J Nurs ; 121(9): 25, 2021 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-34438427

RESUMO

Dapagliflozin (Farxiga) is now approved to reduce the risk of declining kidney function, kidney failure, cardiovascular death, and hospitalization for heart failure in adults with chronic kidney disease with or without type 2 diabetes.


Assuntos
Compostos Benzidrílicos/uso terapêutico , Complicações do Diabetes/prevenção & controle , Diabetes Mellitus Tipo 2/tratamento farmacológico , Glucosídeos/uso terapêutico , Insuficiência Cardíaca/prevenção & controle , Hipoglicemiantes/uso terapêutico , Inibidores do Transportador 2 de Sódio-Glicose/uso terapêutico , Insuficiência Cardíaca/complicações , Humanos , Nefropatias , Fatores de Tempo
8.
Lancet ; 398(10300): 583-598, 2021 08 14.
Artigo em Inglês | MEDLINE | ID: mdl-34370970

RESUMO

BACKGROUND: Tirzepatide is a novel dual glucose-dependent insulinotropic polypeptide and GLP-1 receptor agonist under development for the treatment of type 2 diabetes. We aimed to assess the efficacy and safety of tirzepatide versus titrated insulin degludec in people with type 2 diabetes inadequately controlled by metformin with or without SGLT2 inhibitors. METHODS: In this open-label, parallel-group, multicentre (122 sites), multinational (13 countries), phase 3 study, eligible participants (aged ≥18 years) had a baseline glycated haemoglobin (HbA1c) of 7·0-10·5%, body-mass index of at least 25 kg/m2, stable weight, and were insulin-naive and treated with metformin alone or in combination with an SGLT2 inhibitor for at least 3 months before screening. Participants were randomly assigned (1:1:1:1), using an interactive web-response system, to once-weekly subcutaneous injection of tirzepatide (5, 10, or 15 mg) or once-daily subcutaneous injection of titrated insulin degludec, and were stratified by country, HbA1c, and concomitant use of oral antihyperglycaemic medications. Tirzepatide was initially given at 2·5 mg and the dose was escalated by 2·5 mg every 4 weeks until the assigned dose was reached. Insulin degludec was initially given at 10 U per day and was titrated once weekly to a fasting self-monitored blood glucose of less than 5·0 mmol/L (<90 mg/dL), following a treat-to-target algorithm, for 52 weeks. The primary efficacy endpoint was non-inferiority of tirzepatide 10 mg or 15 mg, or both, versus insulin degludec in mean change from baseline in HbA1c at week 52. Key secondary efficacy endpoints were non-inferiority of tirzepatide 5 mg versus insulin degludec in mean change from baseline in HbA1c at week 52, superiority of all doses of tirzepatide versus insulin degludec in mean change from baseline in HbA1c and bodyweight, and the proportion of participants achieving HbA1c of less than 7·0% (<53 mmol/mol) at week 52. We used a boundary of 0·3% to establish non-inferiority in HbA1c difference between treatments. Efficacy and safety analyses were assessed in the modified intention-to-treat population (all participants who received at least one dose of study drug). This trial is registered with ClinicalTrials.gov, number NCT03882970, and is complete. FINDINGS: Between April 1 and Nov 15, 2019, we assessed 1947 participants for eligibility, 1444 of whom were randomly assigned to treatment. The modified intention-to-treat population was 1437 participants from the tirzepatide 5 mg (n=358), tirzepatide 10 mg (n=360), tirzepatide 15 mg (n=359), and insulin degludec (n=360) groups. From a mean baseline HbA1c of 8·17% (SD 0·91), the reductions in HbA1c at week 52 were 1·93% (SE 0·05) for tirzepatide 5 mg, 2·20% (0·05) for tirzepatide 10 mg, and 2·37% (0·05) for tirzepatide 15 mg, and 1·34% (0·05) for insulin degludec. The non-inferiority margin of 0·3% was met. The estimated treatment difference (ETD) versus insulin degludec ranged from -0·59% to -1·04% for tirzepatide (p<0·0001 for all tirzepatide doses). The proportion of participants achieving a HbA1c of less than 7·0% (<53 mmol/mol) at week 52 was greater (p<0·0001) in all three tirzepatide groups (82%-93%) versus insulin degludec (61%). At week 52, from a baseline of 94·3 kg (SD 20·1), all three tirzepatide doses decreased bodyweight (-7·5 kg to -12·9 kg), whereas insulin degludec increased bodyweight by 2·3 kg. The ETD versus insulin degludec ranged from -9·8 kg to -15·2 kg for tirzepatide (p<0·0001 for all tirzepatide doses). The most common adverse events in tirzepatide-treated participants were mild to moderate gastrointestinal events that decreased over time. A higher incidence of nausea (12-24%), diarrhoea (15-17%), decreased appetite (6-12%), and vomiting (6-10%) was reported in participants treated with tirzepatide than in those treated with insulin degludec (2%, 4%, 1%, and 1%, respectively). Hypoglycaemia (<54 mg/dL or severe) was reported in five (1%), four (1%), and eight (2%) participants on tirzepatide 5, 10, and 15 mg, respectively, versus 26 (7%) on insulin degludec. Treatment discontinuation due to an adverse event was more common in the tirzepatide groups than in the insulin degludec group. Five participants died during the study; none of the deaths were considered by the investigators to be related to the study treatment. INTERPRETATION: In patients with type 2 diabetes, tirzepatide (5, 10, and 15 mg) was superior to titrated insulin degludec, with greater reductions in HbA1c and bodyweight at week 52 and a lower risk of hypoglycaemia. Tirzepatide showed a similar safety profile to that of GLP-1 receptor agonists. FUNDING: Eli Lilly and Company.


Assuntos
Diabetes Mellitus Tipo 2/tratamento farmacológico , Polipeptídeo Inibidor Gástrico/administração & dosagem , Hipoglicemiantes/administração & dosagem , Insulina de Ação Prolongada/uso terapêutico , Metformina/uso terapêutico , Inibidores do Transportador 2 de Sódio-Glicose/uso terapêutico , Feminino , Hemoglobina A Glicada/efeitos dos fármacos , Humanos , Injeções Subcutâneas , Internacionalidade , Masculino , Pessoa de Meia-Idade
9.
J Fam Pract ; 70(6S): S1-S6, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-34432617

RESUMO

LEARNING OBJECTIVES: 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.


Assuntos
Doenças Cardiovasculares/tratamento farmacológico , Doenças Cardiovasculares/prevenção & controle , Inibidores do Transportador 2 de Sódio-Glicose/uso terapêutico , Sistema Cardiovascular/efeitos dos fármacos , Diabetes Mellitus Tipo 2/tratamento farmacológico , Diabetes Mellitus Tipo 2/prevenção & controle , Cardiomiopatias Diabéticas/tratamento farmacológico , Cardiomiopatias Diabéticas/prevenção & controle , Nefropatias Diabéticas/tratamento farmacológico , Nefropatias Diabéticas/prevenção & controle , Inibidores da Dipeptidil Peptidase IV/uso terapêutico , Humanos , Hipoglicemiantes/uso terapêutico , Resultado do Tratamento
10.
Medicine (Baltimore) ; 100(30): e26431, 2021 Jul 30.
Artigo em Inglês | MEDLINE | ID: mdl-34397684

RESUMO

BACKGROUND: Sodium glucose cotransporter 2 (SGLT2) inhibitors and glucagon-like peptide 1 receptor agonists (GLP-1 RAs) have been demonstrated to be able to improve the cardiovascular and renal prognosis in patients with type 2 diabetes (T2D). However, the relative efficacy of various SGLT2 inhibitors and GLP-1 RAs on cardiorenal outcomes is unestablished. METHODS: We searched PubMed and Embase for relevant cardiovascular or renal outcome trials (CVOTs). Endpoints of interest were major adverse cardiovascular events (MACE), stroke, myocardial infarction (MI), cardiovascular death (CVD), all-cause death (ACD), kidney function progression (KFP), and hospitalization for heart failure (HHF). Bayesian network meta-analysis was conducted to produce pooled hazard ratio (HR) and 95% confidence interval (CI). We calculated the probability values of surface under the cumulative ranking curve to rank active and placebo interventions. RESULTS: Fourteen COVTs were included in analysis. Sotagliflozin (HR 0.76, 95% CI 0.61-0.94), subcutaneous semaglutide, and albiglutide lowered MACE versus lixisenatide among others. Sotagliflozin (HR 0.59, 95% CI 0.40-0.89), canagliflozin, and empagliflozin lowered HHF versus subcutaneous semaglutide among others. Dapagliflozin and empagliflozin lowered KFP versus exenatide among others. Empagliflozin and oral semaglutide lowered CVD versus dapagliflozin among others. Sotagliflozin (HR 0.65, 95% CI 0.47-0.91) and albiglutide lowered MI versus ertugliflozin among others. Sotagliflozin (HR 0.56, 95% CI 0.37-0.85) and subcutaneous semaglutide lowered stroke versus empagliflozin among others. Oral semaglutide and empagliflozin lowered ACD versus subcutaneous semaglutide among others. The maximum surface under the cumulative ranking curve values followed sotagliflozin, subcutaneous semaglutide, and albiglutide in lowering MACE; sotagliflozin, canagliflozin, and empagliflozin in lowering HHF; dapagliflozin and empagliflozin in lowering KFP; empagliflozin and oral semaglutide in lowering CVD; sotagliflozin and albiglutide in lowering MI; sotagliflozin and subcutaneous semaglutide in lowering stroke; and oral semaglutide and empagliflozin in lowering ACD. CONCLUSIONS: This updated network meta-analysis reproduced the findings in the first network meta-analysis, and moreover revealed that sotagliflozin was one of the most effective drugs as for lowering MI, stroke, MACE, and HHF, whereas ertugliflozin was not. These findings will provide the according evidence regarding the usage of specific SGLT2 inhibitors and GLP-1 RAs in T2D patients for prevention of specific cardiorenal endpoints.


Assuntos
Diabetes Mellitus Tipo 2/tratamento farmacológico , Receptor do Peptídeo Semelhante ao Glucagon 1/antagonistas & inibidores , Coração/efeitos dos fármacos , Rim/efeitos dos fármacos , Inibidores do Transportador 2 de Sódio-Glicose/efeitos adversos , Diabetes Mellitus Tipo 2/fisiopatologia , Receptor do Peptídeo Semelhante ao Glucagon 1/uso terapêutico , Coração/fisiopatologia , Humanos , Rim/fisiopatologia , Metanálise em Rede , Inibidores do Transportador 2 de Sódio-Glicose/uso terapêutico , Resultado do Tratamento
11.
Int J Mol Sci ; 22(16)2021 Aug 16.
Artigo em Inglês | MEDLINE | ID: mdl-34445519

RESUMO

Cardiovascular disease is the leading cause of morbidity and mortality in diabetes. Recent clinical studies indicate that sodium-glucose co-transporter 2 (SGLT2) inhibitors improve cardiovascular outcomes in patients with diabetes. The mechanism underlying the beneficial effect of SGLT2 inhibitors is not completely clear but may involve direct actions on vascular cells. SGLT2 inhibitors increase the bioavailability of endothelium-derived nitric oxide and thereby restore endothelium-dependent vasodilation in diabetes. In addition, SGLT2 inhibitors favorably regulate the proliferation, migration, differentiation, survival, and senescence of endothelial cells (ECs). Moreover, they exert potent antioxidant and anti-inflammatory effects in ECs. SGLT2 inhibitors also inhibit the contraction of vascular smooth muscle cells and block the proliferation and migration of these cells. Furthermore, studies demonstrate that SGLT2 inhibitors prevent postangioplasty restenosis, maladaptive remodeling of the vasculature in pulmonary arterial hypertension, the formation of abdominal aortic aneurysms, and the acceleration of arterial stiffness in diabetes. However, the role of SGLT2 in mediating the vascular actions of these drugs remains to be established as important off-target effects of SGLT2 inhibitors have been identified. Future studies distinguishing drug- versus class-specific effects may optimize the selection of specific SGLT2 inhibitors in patients with distinct cardiovascular pathologies.


Assuntos
Complicações do Diabetes/prevenção & controle , Inibidores do Transportador 2 de Sódio-Glicose/farmacologia , Remodelação Vascular/efeitos dos fármacos , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/uso terapêutico , Antioxidantes/farmacologia , Antioxidantes/uso terapêutico , Complicações do Diabetes/metabolismo , Células Endoteliais/citologia , Células Endoteliais/efeitos dos fármacos , Células Endoteliais/metabolismo , Humanos , Óxido Nítrico/metabolismo , Inibidores do Transportador 2 de Sódio-Glicose/uso terapêutico
13.
Lancet ; 398(10296): 262-276, 2021 07 17.
Artigo em Inglês | MEDLINE | ID: mdl-34216571

RESUMO

SGLT2 inhibitors and GLP-1 receptor agonists are used in patients with type 2 diabetes as glucose lowering therapies, with additional benefits of weight loss and blood pressure reduction. Data from cardiovascular outcome trials have highlighted that these drugs confer protection against major cardiovascular disease in those with established atherosclerotic cardiovascular disease, reduce the risk of admission to hospital for heart failure, and reduce cardiovascular and all-cause mortality. Ongoing research using hard renal endpoints such as end stage kidney disease rather than surrogate markers might clarify the renoprotective benefits of both agents. When used for glucose lowering, SGLT2 inhibitors are most effective if the estimated glomerular filtration rate is more than 60 ml per min per 1·73m2 at initiation and should be avoided where there is a risk of diabetic ketoacidosis. GLP-1 receptor agonists are contraindicated in those with a history of medullary thyroid cancer and used with caution in patients with a history of pancreatitis of a known cause. These drugs are now second-line, or even arguably first-line, glucose lowering therapies in patients with cardiorenal disease, irrespective of glycaemic control. If an SGLT2 inhibitor or GLP-1 receptor agonist is considered suitable in patients with type 2 diabetes, treatment should be prioritised according to existing evidence: GLP-1 receptor agonists should be considered in patients at a high risk of, or with established, cardiovascular disease and SGLT2 inhibitors considered for patients with heart failure (with reduced ejection fraction) or chronic kidney disease (with or without established cardiovascular disease). There is now compelling data on the benefits of these drugs for a range of other clinical indications even without type 2 diabetes, including for GLP-1 receptor agonists in patients with obesity and overweight with weight-related comorbidities.


Assuntos
Diabetes Mellitus Tipo 2/tratamento farmacológico , Receptor do Peptídeo Semelhante ao Glucagon 1/uso terapêutico , Inibidores do Transportador 2 de Sódio-Glicose/uso terapêutico , Insuficiência Cardíaca/prevenção & controle , Humanos , Inibidores do Transportador 2 de Sódio-Glicose/farmacologia
14.
Medicine (Baltimore) ; 100(27): e26417, 2021 Jul 09.
Artigo em Inglês | MEDLINE | ID: mdl-34232173

RESUMO

BACKGROUND: Currently, there are a number of sodium glucose co-transport-2 (SGLT2) inhibitors that are under development or in clinical trials. Prior meta-analyses had established the safety and efficacy of SGLT2 inhibitors in type 1 diabetes mellitus (T1DM), but with low level of evidences and inconsistent conclusions. However, recently many new randomized clinical trials (RCTs) have been published, we hence try to design a study protocol to assess the effect of SGLT2 inhibitors on cardiovascular events via a comprehensive meta-analysis of data from much more RCTs, including sensitivity and subgroup analyses. METHODS: We will follow the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) reporting guidelines to conduct this meta-analysis. Two investigators will perform a systematic search of scientific literature in the databases (from conception through June 12, 2021), including PubMed, Embase, and Cochrane Central Register of Controlled Trials. This meta-analysis will be conducted using RevMan statistical software. The risk of bias for each included study will be assessed using the Cochrane Risk of Bias Assessment Tool. RESULTS: Our protocol is conceived to test the hypothesis that SGLT2 inhibitors could lead to better outcomes in patients presenting with T1DM. REGISTRATION NUMBER: 10.17605/OSF.IO/ZD8WX.


Assuntos
Diabetes Mellitus Tipo 1/tratamento farmacológico , Hipoglicemiantes/uso terapêutico , Inibidores do Transportador 2 de Sódio-Glicose/uso terapêutico , Diabetes Mellitus Tipo 1/sangue , Controle Glicêmico , Humanos
15.
Medicine (Baltimore) ; 100(28): e26561, 2021 Jul 16.
Artigo em Inglês | MEDLINE | ID: mdl-34260534

RESUMO

BACKGROUND: The factors affecting the efficacy of gliflozins in patients with heart failure (HF) are not clear. We aimed to evaluate the effects of 11 important factors on the efficacy of gliflozins in HF patients. METHODS: Randomized trials assessing gliflozins in HF patients were included. The outcome of interest was composite HF outcome, a composite of cardiovascular death, or hospitalization for HF. Meta-analysis was done according to 11 factors: status of type 2 diabetes, sex, use of angiotensin receptor-neprilysin inhibitor, age, history of hospitalization for HF, estimated glomerular filtration rate, body mass index, New York Heart Association (NYHA) class, race, region, and left ventricular ejection fraction. RESULTS: Compared with placebo, gliflozins reduced the risk of composite HF outcome by 14% in the subgroup of patients with NYHA class III or IV (hazard ratios [HR] 0.86, 95% confidence intervals [CI] 0.75-0.99), by 34% in the subgroup of patients with NYHA class II (HR 0.66, 95% CI 0.59-0.74), and by 85% in the subgroup of patients with NYHA class I (HR 0.15, 95% CI 0.03-0.73). This between-group difference was approximate to statistical significance (Psubgroup = .06). The benefit of gliflozins in HF patients was not affected by the other 10 factors (Psubgroup ≥ .123). CONCLUSIONS: Gliflozins are applicable for a broad population of HF patients as for preventing HF events, while gliflozins may lead to greater benefits in patients with mild HF than in those with moderate to severe HF.


Assuntos
Insuficiência Cardíaca/tratamento farmacológico , Inibidores do Transportador 2 de Sódio-Glicose/uso terapêutico , Fatores Etários , Índice de Massa Corporal , Grupos de Populações Continentais , Diabetes Mellitus Tipo 2/epidemiologia , Taxa de Filtração Glomerular , Insuficiência Cardíaca/epidemiologia , Hospitalização/estatística & dados numéricos , Humanos , Ensaios Clínicos Controlados Aleatórios como Assunto , Fatores Sexuais , Inibidores do Transportador 2 de Sódio-Glicose/administração & dosagem , Volume Sistólico
16.
Int J Mol Sci ; 22(14)2021 Jul 16.
Artigo em Inglês | MEDLINE | ID: mdl-34299225

RESUMO

COVID-19 infection poses an important clinical therapeutic problem, especially in patients with coexistent diseases such as type 2 diabetes. Potential pathogenetic links between COVID-19 and diabetes include inflammation, effects on glucose homeostasis, haemoglobin deoxygenation, altered immune status and activation of the renin-angiotensin-aldosterone system (RAAS). Moreover, drugs often used in the clinical care of diabetes (dipeptidyl peptidase 4 inhibitors, glucagon-like peptide 1 receptor agonists, sodium-glucose cotransporter 2 inhibitors, metformin and insulin) may influence the course of SARS-CoV-2 infection, so it is very important to verify their effectiveness and safety. This review summarises the new advances in diabetes therapy and COVID-19 and provides clinical recommendations that are essential for medical doctors and for patients suffering from type 2 diabetes.


Assuntos
COVID-19/terapia , Diabetes Mellitus Tipo 2/terapia , Inibidores da Enzima Conversora de Angiotensina/uso terapêutico , COVID-19/complicações , COVID-19/epidemiologia , COVID-19/fisiopatologia , Diabetes Mellitus Tipo 2/fisiopatologia , Diabetes Mellitus Tipo 2/virologia , Inibidores da Dipeptidil Peptidase IV/uso terapêutico , Receptor do Peptídeo Semelhante ao Glucagon 1/agonistas , Humanos , Hipoglicemiantes/uso terapêutico , Insulina/uso terapêutico , Metformina/uso terapêutico , SARS-CoV-2/isolamento & purificação , Inibidores do Transportador 2 de Sódio-Glicose/uso terapêutico
17.
Kardiologiia ; 61(6): 4-10, 2021 Jul 01.
Artigo em Russo, Inglês | MEDLINE | ID: mdl-34311683

RESUMO

Major principles for treatment of chronic heart failure with reduced left ventricular ejection fraction <40% (HFrEF) include a "triple neurohormonal blockade" as a main approach. However, in recent 6 years, two new classes of drugs for the treatment of HFrEF have appeared, which beneficially influence the prognosis. These drugs are angiotensin receptor neprilysin inhibitors (ARNI) and type 2 sodium-glucose cotransporter 2 (SGLT2) inhibitors.Aim    To compare the net effect of simultaneous treatment with ARNI and SGLT2 inhibitors with the triple neurohormonal blockade in stable or decompensated patients with CHF based on Russian data.Material and methods    We analyzed the risk of death per 100 patient-years in patients with HFrEF. Stable patients were followed up at the A.L. Myasnikov Institute of Cardiology (presently, A.L. Myasnikov Research Institute of Clinical Cardiology of the National Medical Research Center of Cardiology) from 2006 through 2007; data from the EPOCH-Decompensation-CHF study were used for decompensated patients (12.2 % and 36.8 %, respectively).Results    When patients with stable HFrEF were successively switched from renin-angiotensin-aldosterone system (RAAS) inhibitors to ARNI (-16 %) and subsequently supplemented with SGLT2 (-13 %) the risk of death per 100 patient-years decreased from 12.2 % to 8.9 % (total risk decreased by 27 %; to save one patient the ARNI+ SGLT2 combination has to be prescribed to 30 patients). The estimated risk of death upon discharge from the hospital for the patients with decompensated CHF switched from RAAS inhibitors to ARNI (-16 %) and subsequently supplemented with SGLT2 (-13 %) was 26.9 deaths per 100 patient-years, whereas the number of patients to be treated for saving one life was only 10. Based on available data that demonstrate a greater effect of ARNI+ SGLT2 in patients immediately after CHF aggravation, the risk of death was recalculated. According to this analysis, the death rate per 1000 patient-years decreased from 36.8 to 19.9 % (relative risk decrease, 46 %), and to save one life only 6 patients had to be treated after they have achieved compensation of HFrEF.Conclusions    This analysis shows the importance of early initiation of the ARNI+ SGLT2 therapy in patients with both decompensated and with stable HFrEF.


Assuntos
Antagonistas de Receptores de Angiotensina/uso terapêutico , Insuficiência Cardíaca , Neprilisina , Inibidores do Transportador 2 de Sódio-Glicose/uso terapêutico , Angiotensinas , Glucose , Insuficiência Cardíaca/tratamento farmacológico , Humanos , Neprilisina/antagonistas & inibidores , Prognóstico , Federação Russa , Sódio , Volume Sistólico , Função Ventricular Esquerda
18.
BMJ Open ; 11(7): e049130, 2021 07 09.
Artigo em Inglês | MEDLINE | ID: mdl-34244276

RESUMO

OBJECTIVES: Assess values, preferences and burden of treatment that patients with type 2 diabetes consider when initiating glucagon-like peptide-1 receptor agonists (GLP-1 RA) or sodium-glucose cotransporter-2 inhibitors (SGLT-2i) compared with other glucose-lowering options. METHODS: Paired reviewers independently included studies reporting quantitative or qualitative methods to assess values, preferences and burden of treatment reported by patients with type 2 diabetes regarding the initiation of GLP-1 RA or SGLT-2i over other alternatives. A systematic search in MEDLINE, Scopus, EMBASE, Web of Science and Cochrane Central Register of Controlled Trials from inception until May 2020 was performed by an experienced librarian. Risk of bias was assessed with a specifically designed tool for values and preferences studies. RESULTS: 17 studies (7296 patients) proved eligible. Studies fulfilling criteria for SGLT-2i were not identified. Five studies (2662 patients) evaluated preferences for GLP-1 RA compared with other glucose-lowering medications. 12 studies (4634 patients) evaluated preferences between, at least, two kinds of GLP-1 RA or their injection devices based on the following attributes: efficacy, dose, application frequency, device characteristics. Among studies comparing GLP-1 RA to other glucose-lowering medications, some preferences were observed for dypeptil peptidase-4 inhibitors compared with once daily liraglutide. Comparing different attributes of GLP-1 RA drugs and devices, cardiovascular risk reduction, glucose lowering potential, once weekly and simple administered regimens were the most preferred. CONCLUSIONS: As no evidence for preferences on SGLT-2i was available, only preferences for GLP-1 RA were assessed; however, evidence is still limited for the latter. Studies comparing preferences for GLP1-RA to other glucose-lowering alternatives only included twice daily or once daily injection regimens of GLP-1 RA drugs. According to our findings, once weekly alternatives are widely preferred than the formers. The extent to which patients with type 2 diabetes value reduced adverse cardiovascular and kidney outcomes, weighed benefits against harms and burden of treatment is limited and with very low certainty. PROSPERO REGISTRATION NUMBER: CRD42020159284.


Assuntos
Diabetes Mellitus Tipo 2 , Preparações Farmacêuticas , Inibidores do Transportador 2 de Sódio-Glicose , Adulto , Diabetes Mellitus Tipo 2/tratamento farmacológico , Receptor do Peptídeo Semelhante ao Glucagon 1 , Humanos , Hipoglicemiantes/uso terapêutico , Inibidores do Transportador 2 de Sódio-Glicose/uso terapêutico
19.
Int Heart J ; 62(4): 843-849, 2021 Jul 30.
Artigo em Inglês | MEDLINE | ID: mdl-34276009

RESUMO

The DAPA-HF trial demonstrated that sodium-glucose cotransporter 2 inhibitors (SGLT2i) reduced worsening heart failure (HF) events in chronic HF patients with or without type 2 diabetic mellitus (T2DM). However, it remains unclear whether the effectiveness of SGLT2i is also observed in patients with decompensated HF irrespective of HbA1c level. Eighty-one T2DM patients hospitalized due to decompensated HF were enrolled and divided into 2 groups according to their HbA1c levels (group H, HbA1c 6.9-13.0%, n = 41; group L, HbA1c < 6.9%, n = 40). After the initial management of HF, one of the SGLT2i (canagliflozin 100 mg/day or dapagliflozin 5 mg/day or empagliflozin 10 mg/day) was non-randomly administered, and clinical parameters associating with HF and T2DM were followed for 7 days. No symptomatic hypoglycemia was observed in any patient. In both groups, urine glucose excretion was increased significantly after the administration of SGLT2i. However, its amount was greater in group H than group L. Urine volume was increased significantly at day 1 in both groups. Urine volume returned to the baseline after one week in group L. In contrast, the increase in urine volume persisted at least for one week in group H. Of note, a decrease in B-type natriuretic peptide levels after the initiation of SGLT2i was observed in both groups similarly despite differences in urine output and excretion of urine glucose. In conclusion, SGLT2i can improve decompensated HF in patients with T2DM irrespective of the HbA1c level.


Assuntos
Diabetes Mellitus Tipo 2/tratamento farmacológico , Hemoglobina A Glicada/metabolismo , Insuficiência Cardíaca/tratamento farmacológico , Inibidores do Transportador 2 de Sódio-Glicose/uso terapêutico , Idoso , Idoso de 80 Anos ou mais , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/urina , Feminino , Insuficiência Cardíaca/sangue , Insuficiência Cardíaca/complicações , Insuficiência Cardíaca/urina , Humanos , Masculino , Estudos Prospectivos
20.
Int Heart J ; 62(4): 885-890, 2021 Jul 30.
Artigo em Inglês | MEDLINE | ID: mdl-34276019

RESUMO

Sodium-glucose cotransporter 2 inhibitor (SGLT2i) reduces mortality and morbidity in patients with chronic heart failure (HF). However, the clinical implication of SGLT2i therapy in patients with acute decompensated HF remains uncertain. We prospectively studied 86 type 2 diabetic mellitus (T2DM) patients (71.8 ± 12.1 years, 55 men) who were hospitalized for acute decompensated HF and received SGLT2i during the index hospitalization. Among the patients, 56 continued SGLT2i at discharge and 30 did not. The continued group experienced fewer HF re-hospitalizations than the discontinued group (24% versus 39%, P = 0.008) with a hazard ratio of 0.29 (95% confidence interval 0.10-0.85) adjusted for other significant potential confounders. In conclusion, long-term SGLT2i therapy might prevent unplanned HF re-hospitalization in patients with T2DM and acute decompensated HF.


Assuntos
Diabetes Mellitus Tipo 2/tratamento farmacológico , Insuficiência Cardíaca/tratamento farmacológico , Inibidores do Transportador 2 de Sódio-Glicose/uso terapêutico , Idoso , Idoso de 80 Anos ou mais , Diabetes Mellitus Tipo 2/complicações , Feminino , Insuficiência Cardíaca/complicações , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Resultado do Tratamento
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