RESUMEN
Objective: Evaluate the effects of sodium-glucose cotransporter 2 inhibitor (SGLT2i) on cardiovascular and cerebrovascular diseases. Methods: Articles of SGLT2i on cardiovascular and cerebrovascular diseases were searched. Two authors independently screened the literature, extracted the data, assessed the quality of the study and performed statistical analyses using Review Manager 5.4. Results: Random-effect model was used to merge the OR values, and the pooled effect showed that SGLT2i had significant preventive effects on cardiovascular death (OR=0.76, 95%CI 0.64 to 0.89), myocardial infarction (OR=0.90, 95%CI 0.84 to 0.96), heart failure (OR=0.69, 95%CI 0.64 to 0.74) and all-cause mortality (OR=0.65, 95%CI 0.58 to 0.73). Empagliflozin, dapagliflozin and canagliflozin all reduced the incidence of heart failure (OR=0.72, 95%CI 0.64 to 0.82; OR=0.56, 95%CI 0.39 to 0.80; OR=0.62, 95%CI 0.53 to 0.73), but only dapagliflozin displayed a favorable effect on inhibiting stroke (OR=0.78, 95%CI 0.63 to 0.98). SGLT2i could prevent stroke (OR=0.86, 95%CI 0.75 to 0.99), heart failure (OR=0.63, 95%CI 0.56 to 0.70) and all-cause mortality (OR=0.64, 95%CI 0.57 to 0.72) compared to DPP-4i. Furthermore, SGLT2i could reduce the incidence of heart failure (OR=0.72, 95%CI 0.67 to 0.77) and cardiovascular death (OR=0.72, 95%CI 0.54 to 0.95) in patients with high-risk factors. Conclusions: SGLT2i affects cardiovascular death, myocardial infarction, heart failure and all-cause mortality. Only dapagliflozin displayed a favorable effect on inhibiting stroke. SGLT2i could prevent stroke, heart failure and all-cause mortality compared to DPP-4i. In addition, SGLT2i significantly reduced the development of heart failure and cardiovascular death in patients with high-risk factors. Systematic review registration: https://www.crd.york.ac.uk/prospero, identifier CRD42024532783.
Asunto(s)
Enfermedades Cardiovasculares , Trastornos Cerebrovasculares , Diabetes Mellitus Tipo 2 , Inhibidores del Cotransportador de Sodio-Glucosa 2 , Humanos , Inhibidores del Cotransportador de Sodio-Glucosa 2/uso terapéutico , Enfermedades Cardiovasculares/mortalidad , Enfermedades Cardiovasculares/prevención & control , Enfermedades Cardiovasculares/tratamiento farmacológico , Trastornos Cerebrovasculares/prevención & control , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Diabetes Mellitus Tipo 2/complicaciones , Compuestos de Bencidrilo/uso terapéutico , Glucósidos/uso terapéutico , Ensayos Clínicos Controlados como Asunto , Hipoglucemiantes/uso terapéuticoRESUMEN
BACKGROUND: Heart failure (HF) is an emerging pandemic associated with increased mortality, recurrent hospitalizations, and reduced quality of life. Guideline-directed medical therapy has been shown to improve outcomes, particularly in patients with HF with reduced ejection fraction (HFrEF). The main goal of HF clinics is optimizing medical therapy. OBJECTIVES: To assess the impact of our HF clinic on medical therapy and clinical outcomes. METHODS: We obtained demographic, echocardiographic, and clinical data of patients listed in our HF clinic during a 4-year period. Medical therapy was evaluated based on patient reports and documented data. Recurrent admissions for HF were documented. RESULTS: A total of 317 patients (74.1% male, median age 66 years, IQR 55-74) were listed in the clinic with a total of 1140 visits. Of these patients, 62.5% had HFrEF, 20.5% presented with mildly reduced ejection fraction, and 17% showed preserved ejection fraction at the time of the first visit. The use of sodium glucose co-transporter 2 inhibitors and mineralocorticoid receptor antagonists was optimized in 92% and 91% of the patients, respectively. In the subgroup of patients with HFrEF, the use of angiotensin-receptor antagonist/neprilysin inhibitor increased from 22.6% to 87.9% (P < 0.001) and SGLT2 inhibitor use increased from 49.2% to 92% (P < 0.001). During the follow-up period (2.2 years, IQR 1.1-3.1), 203 patients (64%) were readmitted to the hospital for HF at least once. The rate of readmissions decreased over time. CONCLUSIONS: An HF clinic plays an important role in optimizing medical therapy and reducing readmissions.
Asunto(s)
Insuficiencia Cardíaca , Antagonistas de Receptores de Mineralocorticoides , Volumen Sistólico , Humanos , Insuficiencia Cardíaca/terapia , Insuficiencia Cardíaca/fisiopatología , Insuficiencia Cardíaca/tratamiento farmacológico , Masculino , Femenino , Persona de Mediana Edad , Anciano , Volumen Sistólico/fisiología , Antagonistas de Receptores de Mineralocorticoides/uso terapéutico , Hospitalización/estadística & datos numéricos , Resultado del Tratamiento , Antagonistas de Receptores de Angiotensina/uso terapéutico , Ecocardiografía/métodos , Inhibidores del Cotransportador de Sodio-Glucosa 2/uso terapéutico , Israel/epidemiología , Readmisión del Paciente/estadística & datos numéricos , Estudios Retrospectivos , Instituciones de Atención Ambulatoria/estadística & datos numéricosRESUMEN
This meta-analysis investigated efficacy of dapagliflozin as adjunctive therapy for patients with type 2 diabetes mellitus (T2DM) and chronic kidney disease (CKD) stages 2-5. A systematic search was conducted of selected databases for randomised controlled trials that reported the mean change in estimated glomerular filtration rate (eGFR) and urine albumin-creatinine ratio (UACR) from baseline. Out of 1,682 identified studies, 9 trials comprising 13,057 patients were included. A pooled estimate of 5 studies indicated that dapagliflozin did not affect eGFR; however, in 2 studies, it significantly reduced chronic eGFR decline compared to placebo (mean difference [MD] ± 2.74; 95% confidence interval [CI]: 1.55, 3.92; P <0.00001). Additionally, a pooled estimate of 4 studies showed that dapagliflozin significantly reduced UACR (MD -23.99%; 95% CI: -34.82--13.15; P <0.0001; I2 = 0%). Therefore, long-term use of dapagliflozin significantly attenuates eGFR decline and reduces albuminuria in patients with T2DM and CKD.
Asunto(s)
Compuestos de Bencidrilo , Diabetes Mellitus Tipo 2 , Glucósidos , Insuficiencia Renal Crónica , Humanos , Glucósidos/uso terapéutico , Glucósidos/farmacología , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Diabetes Mellitus Tipo 2/complicaciones , Compuestos de Bencidrilo/uso terapéutico , Compuestos de Bencidrilo/farmacología , Insuficiencia Renal Crónica/tratamiento farmacológico , Insuficiencia Renal Crónica/fisiopatología , Progresión de la Enfermedad , Tasa de Filtración Glomerular/efectos de los fármacos , Inhibidores del Cotransportador de Sodio-Glucosa 2/uso terapéutico , Inhibidores del Cotransportador de Sodio-Glucosa 2/farmacología , Femenino , MasculinoRESUMEN
Background: Sodiumâglucose cotransporter-2 (SGLT2) inhibitors offer glycaemic and cardiorenal benefits in the early stage of chronic kidney disease (CKD). However, the use of SGLT2 inhibitors may increase the risk of genitourinary tract infection (GUTI). Angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) may also cause deterioration of kidney function. The long-term follow-up of cardiorenal outcomes and GUTI incidence in patients with advanced CKD receiving SGLT2 inhibitors combined with ACEIs/ARBs should be further investigated. Methods: We analysed data from 5,503 patients in Taiwan's Taipei Medical University Research Database (2016-2020) who were part of a pre-end-stage renal disease (ESRD) program (CKD stages 3-5) and received ACEIs/ARBs. SGLT2 inhibitor users were matched 1:4 with nonusers on the basis of sex, CKD, and program entry duration. Results: The final cohort included 205 SGLT2 inhibitor users and 820 nonusers. SGLT2 inhibitor users experienced a significant reduction in ESRD/dialysis risk (aHR = 0.35, 95% CI = 0.190.67), and SGLT2 inhibitor use was not significantly associated with acute kidney injury or acute kidney disease risk. Among SGLT2 inhibitor users, those with a history of cardiovascular disease (CVD) had greater CVD rates. Conversely, those without a CVD history had lower rates of congestive heart failure, arrhythmia, acute pulmonary oedema, and acute myocardial infarction, although the differences were not statistically significant. Notably, SGLT2 inhibitor usage was associated with a greater GUTI incidence (aHR = 1.78, 95% CI = 1.122.84) shortly after initiation, irrespective of prior GUTI history status. Conclusion: Among patients with CKD stages 3-5, SGLT2 inhibitor use was linked to increased GUTI incidence, but it also significantly reduced the ESRD/dialysis risk without an episodic AKI or AKD risk. Clinical physicians should consider a personalized medicine approach by balancing GUTI episodes and cardiorenal outcomes for advanced CKD patients receiving SGLT2 inhibitors.
Asunto(s)
Antagonistas de Receptores de Angiotensina , Inhibidores de la Enzima Convertidora de Angiotensina , Insuficiencia Renal Crónica , Inhibidores del Cotransportador de Sodio-Glucosa 2 , Humanos , Inhibidores del Cotransportador de Sodio-Glucosa 2/efectos adversos , Inhibidores del Cotransportador de Sodio-Glucosa 2/uso terapéutico , Taiwán/epidemiología , Masculino , Femenino , Persona de Mediana Edad , Estudios Retrospectivos , Incidencia , Anciano , Antagonistas de Receptores de Angiotensina/efectos adversos , Antagonistas de Receptores de Angiotensina/uso terapéutico , Insuficiencia Renal Crónica/epidemiología , Insuficiencia Renal Crónica/complicaciones , Inhibidores de la Enzima Convertidora de Angiotensina/efectos adversos , Inhibidores de la Enzima Convertidora de Angiotensina/uso terapéutico , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Diabetes Mellitus Tipo 2/complicaciones , Diabetes Mellitus Tipo 2/epidemiologíaAsunto(s)
Insuficiencia Cardíaca , Inhibidores del Cotransportador de Sodio-Glucosa 2 , Humanos , Insuficiencia Cardíaca/tratamiento farmacológico , Inhibidores del Cotransportador de Sodio-Glucosa 2/uso terapéutico , Inhibidores del Cotransportador de Sodio-Glucosa 2/efectos adversos , Enfermedad Aguda , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Glucósidos/uso terapéutico , Glucósidos/efectos adversos , Glucósidos/administración & dosificación , Ensayos Clínicos Controlados Aleatorios como Asunto , Compuestos de Bencidrilo/uso terapéutico , Compuestos de Bencidrilo/efectos adversosRESUMEN
Sodium-glucose cotransporter-2 inhibitors (SGLT2i) inhibit urinary glucose and sodium reabsorption in the proximal tubule of the nephron and result in glucosuria, natriuresis and diuresis. In patients with T2DM who have atherosclerotic cardiovascular (CV) disease or CV risk factors, SGLT2is have been shown to reduce major CV events and heart failure (HF) hospitalization. The greatest and most consistent effect of SGLT2is in these trials was found to be reduction in HF hospitalization, which raised the possibility of clinical benefit of SGLT2i in HF patients. In DAPA-HF and EMPEROR-Reduced trials in HFrEF patients with or without T2DM, SGLT2is, dapagliflozin and empagliflozin treatment on top of standard HF therapy has been shown to have clear clinical benefit in reducing primary endpoint of CV mortality or HF hospitalization and improving quality of life. Recently published EMPEROR-Preserved and DELIVER trials showed that SGLT2is were also very effective in the treatment of HFpEF (EF >40%). Furthermore, SGLT2is have also been shown to have potential in improving clinical outcomes in hospitalized acute HF patients in EMPULSE and DICTATE-AHF trials. All of this evidence has changed guidelines recommended therapies, not only for HFrEF but also for HFpEF treatment. The aim of this article is to provide a comprehensive overview focused on the role of SGLT2i in the treatment of HF based on the recent evidence.
Asunto(s)
Insuficiencia Cardíaca , Inhibidores del Cotransportador de Sodio-Glucosa 2 , Humanos , Insuficiencia Cardíaca/tratamiento farmacológico , Inhibidores del Cotransportador de Sodio-Glucosa 2/uso terapéutico , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Diabetes Mellitus Tipo 2/complicaciones , Compuestos de Bencidrilo/uso terapéutico , Hospitalización , Glucósidos/uso terapéuticoRESUMEN
AIM: To explore the views of general practitioners (GPs) and nurses on type 2 diabetes (T2D) management, including the use of recently funded T2D medications in New Zealand (NZ) and their perceived barriers to providing optimal care. BACKGROUND: T2D is a significant health concern in NZ, particularly among Maori and Pacific adults. Characterised by prolonged hyperglycaemia, T2D is generally a progressive condition requiring long-term care. METHODS: Semi-structured interviews were conducted between July and December 2022 with 21 primary care clinicians (10 GPs and 11 nurses/nurse prescribers) from nine different general practice clinics across the Auckland and Waikato regions of NZ. Framework analysis was conducted to identify common themes in clinicians' perceptions and experiences with T2D management. FINDINGS: Three themes were identified: health-system factors, new medications, and solution-based approaches. Lack of clinician time, healthcare funding, staff shortages, and burn-out were identified as barriers to T2D management under health-system factors. The two newly funded medications, empagliflozin and dulaglutide, were deemed to be a positive change for T2D care in that they improved patient satisfaction and clinical outcomes, but several clinicians were hesitant to prescribe these medications. Participants suggested that additional education and specialist diabetes support would be helpful to inform optimal medication prescribing and that better use of a multi-disciplinary team (clinical and support staff) could support T2D care by reducing workload, addressing cultural gaps in healthcare delivery, and reducing burnout. An improved primary care work environment, including appropriate professional development to support prescribing of new medications and the value of collaboration with a non-regulated workforce, may be required to facilitate optimal T2D management in primary care. Future research should focus on interventions to increase support for both clinical teams and patients while adopting a culturally appropriate approach to increase patient satisfaction and improve health outcomes.
Asunto(s)
Diabetes Mellitus Tipo 2 , Médicos Generales , Atención Primaria de Salud , Investigación Cualitativa , Inhibidores del Cotransportador de Sodio-Glucosa 2 , Humanos , Nueva Zelanda , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Masculino , Médicos Generales/psicología , Femenino , Inhibidores del Cotransportador de Sodio-Glucosa 2/uso terapéutico , Adulto , Persona de Mediana Edad , Hipoglucemiantes/uso terapéutico , Receptor del Péptido 1 Similar al Glucagón/agonistas , Actitud del Personal de Salud , Pautas de la Práctica en Medicina/estadística & datos numéricos , Enfermeras y Enfermeros/psicología , Entrevistas como AsuntoAsunto(s)
Tasa de Filtración Glomerular , Inhibidores del Cotransportador de Sodio-Glucosa 2 , Humanos , Inhibidores del Cotransportador de Sodio-Glucosa 2/uso terapéutico , Inhibidores del Cotransportador de Sodio-Glucosa 2/efectos adversos , Tasa de Filtración Glomerular/efectos de los fármacos , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Diabetes Mellitus Tipo 2/sangre , Nefropatías Diabéticas/tratamiento farmacológicoRESUMEN
Aim: Sodium-glucose cotransporter protein 2 (SGLT2) inhibitors have been shown to have renoprotective effects in clinical studies. For further validation in terms of genetic variation, drug-targeted Mendelian randomization (MR) was used to investigate the causal role of SGLT2 inhibition on eGFR effects. Methods: Genetic variants representing SGLT2 inhibition were selected as instrumental variables. Drug target Mendelian randomization analysis was used to investigate the relationship between SGLT2 inhibitors and eGFR. The IVW method was used as the primary analysis method. As a sensitivity analysis, GWAS pooled data from another CKDGen consortium was used to validate the findings. Results: MR results showed that hemoglobin A1c (HbA1c) levels, regulated by the SLC5A2 gene, were negatively correlated with eGFR (IVW ß -0.038, 95% CI -0.061 to -0.015, P = 0.001 for multi-ancestry populations; IVW ß -0.053, 95% CI -0.077 to -0.028, P = 2.45E-05 for populations of European ancestry). This suggests that a 1-SD increase in HbA1c levels, regulated by the SLC5A2 gene, is associated with decreased eGFR. Mimicking pharmacological inhibition by lowering HbA1c per 1-SD unit through SGLT2 inhibition reduces the risk of eGFR decline, demonstrating a renoprotective effect of SGLT2 inhibitors. HbA1c, regulated by the SLC5A2 gene, was negatively correlated with eGFR in both validation datasets (IVW ß -0.027, 95% CI -0.046 to -0.007, P=0.007 for multi-ancestry populations, and IVW ß -0.031, 95% CI -0.050 to -0.011, P=0.002 for populations of European origin). Conclusions: The results of this study indicate that the SLC5A2 gene is causally associated with eGFR. Inhibition of SLC5A2 gene expression was linked to higher eGFR. The renoprotective mechanism of SGLT2 inhibitors was verified from the perspective of genetic variation.
Asunto(s)
Tasa de Filtración Glomerular , Análisis de la Aleatorización Mendeliana , Inhibidores del Cotransportador de Sodio-Glucosa 2 , Transportador 2 de Sodio-Glucosa , Humanos , Inhibidores del Cotransportador de Sodio-Glucosa 2/uso terapéutico , Inhibidores del Cotransportador de Sodio-Glucosa 2/farmacología , Transportador 2 de Sodio-Glucosa/genética , Transportador 2 de Sodio-Glucosa/metabolismo , Hemoglobina Glucada/metabolismo , Hemoglobina Glucada/análisis , Polimorfismo de Nucleótido Simple , Estudio de Asociación del Genoma CompletoRESUMEN
Background: Recent clinical studies suggest protective effects of SGLT2 inhibitors on kidney disease outcome. Chronic hypoxia has a critical role in kidney disease development, thus we speculated that canagliflozin, an SGLT2 inhibitor, can improve kidney oxygenation. Methods: A single-arm study was conducted to investigate the effects of canagliflozin on T2* value, which reflects oxygenation level, in patients with type 2 diabetes (T2D) using repeated blood oxygenation level-dependent MRI (BOLD MRI) examinations. Changes in cortical T2* from before (Day 0) to after single-dose treatment (Day 1) and after five consecutive treatments (Day 5) were evaluated using 12-layer concentric objects (TLCO) and region of interest (ROI) methods. Results: In the full analysis set (n=14 patients), the TLCO method showed no change of T2* with canagliflozin treatment, whereas the ROI method found that cortical T2* was significantly increased on Day 1 but not on Day 5. Sensitivity analysis using TLCO in 13 well-measured patients showed that canagliflozin significantly increased T2* on Day 1 with no change on Day 5, whereas a significant improvement in cortical T2* following canagliflozin treatment was found on both Day 1 and 5 using ROI. Conclusions: Short-term canagliflozin treatment may improve cortical oxygenation and lead to better kidney outcomes in patients with T2D.
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Canagliflozina , Diabetes Mellitus Tipo 2 , Riñón , Imagen por Resonancia Magnética , Oxígeno , Inhibidores del Cotransportador de Sodio-Glucosa 2 , Humanos , Canagliflozina/uso terapéutico , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Diabetes Mellitus Tipo 2/sangre , Masculino , Persona de Mediana Edad , Femenino , Imagen por Resonancia Magnética/métodos , Inhibidores del Cotransportador de Sodio-Glucosa 2/uso terapéutico , Riñón/efectos de los fármacos , Riñón/diagnóstico por imagen , Riñón/metabolismo , Anciano , Oxígeno/sangre , Hipoglucemiantes/uso terapéuticoRESUMEN
Background: Sodium-glucose co-transporter-2 inhibitors (SGLT2i) have cardiovascular (CV) benefits, particularly in reducing the risk of heart failure (HF). Pioglitazone (Pio) has shown potential in decreasing the risks of recurrent stroke, non-fatal myocardial infarction (MI), and all-cause mortality but increasing risks of HF. Our study aimed to examine the synergistic effects on CV outcomes in patients with type 2 diabetes mellitus (T2DM) who received the combined treatment of SGLT2i and Pio. Materials and methods: A total of 117,850 patients with T2DM and without a history of HF were selected as the observational study cohort from the Chang Gung Research Database (CGRD) in Taiwan between January 1, 2016, and December 31, 2019. The primary composite outcome was 4-point major adverse CV events (4P-MACE), including CV death, non-fatal MI, non-fatal ischemic stroke, and hospitalization for HF. The study was divided into four groups: a combined treatment group in which SGLT2i and Pio were used, two individual groups in which SGLT2i or Pio was used separately, and a reference group (non-study drugs). Results: Combined treatment of SGLT2i and Pio had the lowest risk of 4P-MACE (adjusted hazard ratio [aHR], 0.66; 95% confidence interval [CI], 0.54-0.80) compared with the reference group after a mean follow-up of 2.2 years. There was no significant difference in risks of hospitalization for HF (adjusted subdistribution hazard ratio, 0.73; 95% CI, 0.49-1.07) compared with the reference group. Conclusions: In T2DM patients without HF, the combined treatment with SGLT2i and Pio may synergistically provide CV benefits without increasing risks of HF.
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Enfermedades Cardiovasculares , Diabetes Mellitus Tipo 2 , Quimioterapia Combinada , Hipoglucemiantes , Pioglitazona , Inhibidores del Cotransportador de Sodio-Glucosa 2 , Humanos , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Diabetes Mellitus Tipo 2/complicaciones , Pioglitazona/uso terapéutico , Inhibidores del Cotransportador de Sodio-Glucosa 2/uso terapéutico , Masculino , Femenino , Persona de Mediana Edad , Anciano , Hipoglucemiantes/uso terapéutico , Enfermedades Cardiovasculares/epidemiología , Taiwán/epidemiología , Sinergismo Farmacológico , Resultado del Tratamiento , Estudios de SeguimientoAsunto(s)
Diabetes Mellitus Tipo 2 , Hipoglucemiantes , Metformina , Vildagliptina , Humanos , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Metformina/uso terapéutico , Metformina/farmacología , Vildagliptina/farmacología , Vildagliptina/uso terapéutico , Hipoglucemiantes/uso terapéutico , Hipoglucemiantes/farmacología , Glucósidos/uso terapéutico , Glucósidos/farmacología , Glucósidos/efectos adversos , Pirrolidinas/uso terapéutico , Pirrolidinas/farmacología , Pirrolidinas/efectos adversos , Quimioterapia Combinada/métodos , Nitrilos/uso terapéutico , Nitrilos/efectos adversos , Adamantano/análogos & derivados , Adamantano/uso terapéutico , Adamantano/efectos adversos , Compuestos de Bencidrilo/uso terapéutico , Compuestos de Bencidrilo/efectos adversos , Compuestos de Bencidrilo/farmacología , Inhibidores del Cotransportador de Sodio-Glucosa 2/uso terapéutico , Inhibidores del Cotransportador de Sodio-Glucosa 2/farmacología , Inhibidores de la Dipeptidil-Peptidasa IV/uso terapéutico , Inhibidores de la Dipeptidil-Peptidasa IV/farmacologíaRESUMEN
SGLT2 inhibitors (gliflozins) have proven their efficacy in reducing complications due to atherosclerotic cardiovascular disease, heart failure and chronic kidney disease both in placebo-controlled clinical trials and in real-life studies versus other glucose-lowering agents (except GLP-1 analogues) in patients with type 2 diabetes. Hence, observational studies demonstrate that they are poorly used in -clinical practice, including in patients at high cardiorenal risk. -Reasons are multiple and involve physicians, patients and health care system with restricted criteria for prescription and reimbursement in many countries. Bridging the gap between scientific proves from evidence-based medicine and clinical practice represents a major health-care issue.
Les inhibiteurs des SGLT2 (gliflozines) ont prouvé leur efficacité pour réduire le risque des complications de la maladie athéromateuse, de l'insuffisance cardiaque et de la maladie rénale chronique dans des essais cliniques contrôlés versus placebo et dans des études de vraie vie versus les autres antidiabétiques (sauf les analogues du GLP-1) chez des patients avec un diabète de type 2. Pourtant, les études observationnelles démontrent qu'ils sont peu utilisés en pratique clinique, y compris chez des patients à haut risque cardiorénal. Les raisons en sont multiples et impliquent le médecin prescripteur, le patient et, éventuellement, le système de soins avec des critères d'utilisation ou de remboursement restreints. Combler le fossé entre l'évidence scientifique apportée par la médecine factuelle et la pratique clinique représente un enjeu majeur de santé publique.
Asunto(s)
Diabetes Mellitus Tipo 2 , Hipoglucemiantes , Inhibidores del Cotransportador de Sodio-Glucosa 2 , Humanos , Inhibidores del Cotransportador de Sodio-Glucosa 2/uso terapéutico , Inhibidores del Cotransportador de Sodio-Glucosa 2/efectos adversos , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Diabetes Mellitus Tipo 2/complicaciones , Hipoglucemiantes/uso terapéutico , Hipoglucemiantes/efectos adversos , Enfermedades Cardiovasculares/prevención & control , Insuficiencia Cardíaca/tratamiento farmacológico , Medicina Basada en la EvidenciaRESUMEN
BACKGROUND: Sodium-glucose cotransporter 2 inhibitors (SGLT-2is) have demonstrated associations with lowering cardiovascular outcomes in patients with type 2 diabetes mellitus (T2DM). However, the impact of SGLT-2is on individuals at dialysis commencement remains unclear. The aim of this real-world study is to study the association between SGLT-2is and outcomes in patients with T2DM at dialysis commencement. METHODS: This is a retrospective cohort study of electronic health records (EHRs) of patients with T2DM from TriNetX Research Network database between January 1, 2012, and January 1, 2024. New-users using intention to treatment design was employed and propensity score matching was utilized to select the cohort. Clinical outcomes included major adverse cardiac events (MACE) and all-cause mortality. Safety outcomes using ICD-10 codes, ketoacidosis, urinary tract infection (UTI) or genital infection, dehydration, bone fracture, below-knee amputation, hypoglycemia, and achieving dialysis-free status at 90 days and 90-day readmission. RESULTS: Of 49,762 patients with T2DM who initiated dialysis for evaluation, a mere 1.57% of patients utilized SGLT-2is within 3 months after dialysis. 771 SGLT-2i users (age 63.3 ± 12.3 years, male 65.1%) were matched with 771 non-users (age 63.1 ± 12.9 years, male 65.8%). After a median follow-up of 2.0 (IQR 0.3-3.9) years, SGLT-2i users were associated with a lower risk of MACE (adjusted Hazard Ratio [aHR] = 0.52, p value < 0.001), all-cause mortality (aHR = 0.49, p < 0.001). SGLT-2i users were more likely to become dialysis-free 90 days after the index date (aHR = 0.49, p < 0.001). No significant differences were observed in the incidence of ketoacidosis, UTI or genital infection, hypoglycemia, dehydration, bone fractures, below-knee amputations, or 90-day readmissions. CONCLUSIONS: Our findings indicated a lower incidence of all-cause mortality and MACE after long-term follow-up, along with a higher likelihood of achieving dialysis-free status at 90 days in SGLT-2i users. Importantly, they underscored the potential cardiovascular protection and safety of SGLT-2is use in T2DM patients at the onset of dialysis.
Asunto(s)
Enfermedades Cardiovasculares , Bases de Datos Factuales , Diabetes Mellitus Tipo 2 , Diálisis Renal , Inhibidores del Cotransportador de Sodio-Glucosa 2 , Humanos , Inhibidores del Cotransportador de Sodio-Glucosa 2/uso terapéutico , Inhibidores del Cotransportador de Sodio-Glucosa 2/efectos adversos , Masculino , Femenino , Estudios Retrospectivos , Diabetes Mellitus Tipo 2/mortalidad , Diabetes Mellitus Tipo 2/diagnóstico , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Persona de Mediana Edad , Anciano , Resultado del Tratamiento , Factores de Tiempo , Diálisis Renal/efectos adversos , Diálisis Renal/mortalidad , Medición de Riesgo , Enfermedades Cardiovasculares/mortalidad , Enfermedades Cardiovasculares/diagnóstico , Enfermedades Cardiovasculares/epidemiología , Enfermedades Cardiovasculares/prevención & control , Factores de Riesgo , Nefropatías Diabéticas/mortalidad , Nefropatías Diabéticas/diagnóstico , Nefropatías Diabéticas/terapia , Registros Electrónicos de SaludAsunto(s)
Receptor del Péptido 1 Similar al Glucagón , Hipolipemiantes , Inhibidores del Cotransportador de Sodio-Glucosa 2 , Humanos , Inhibidores del Cotransportador de Sodio-Glucosa 2/uso terapéutico , Inhibidores del Cotransportador de Sodio-Glucosa 2/farmacología , Receptor del Péptido 1 Similar al Glucagón/agonistas , Hipolipemiantes/uso terapéutico , Hipoglucemiantes/uso terapéutico , Hipoglucemiantes/farmacología , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Enfermedades Cardiovasculares/prevención & controlRESUMEN
BACKGROUND: Sodium-glucose cotransporter 2 (SGLT2) inhibitors improve health status in heart failure (HF) across the left ejection fraction ejection spectrum. However, the effects of SGLT1 and SGLT2 inhibition on health status are unknown. OBJECTIVES: These prespecified analyses of the SOLOIST-WHF (Effect of Sotagliflozin on Cardiovascular Events in Patients with Type 2 Diabetes Post Worsening Heart Failure) trial examined the effects of sotagliflozin vs placebo on HF-related health status. METHODS: SOLOIST-WHF randomized patients hospitalized or recently discharged after a worsening HF episode to receive sotagliflozin or placebo. The primary endpoint was total number of HF hospitalizations, urgent HF visits, and cardiovascular death. Kansas City Cardiomyopathy Questionnaire-12 (KCCQ-12) score was a prespecified secondary endpoint. This analysis evaluated change in the KCCQ-12 score from baseline to month 4. RESULTS: Of 1,222 patients randomized, 1,113 (91%) had complete KCCQ-12 data at baseline and 4 months. The baseline KCCQ-12 score was low overall (median: 41.7; Q1-Q3: 27.1-58.3) and improved by 4 months in both groups. Sotagliflozin vs placebo reduced the risk of the primary endpoint consistently across KCCQ-12 tertiles (Ptrend = 0.54). Sotagliflozin-treated patients vs those receiving placebo experienced modest improvement in KCCQ-12 at 4 months (adjusted mean change: 4.1 points; 95% CI: 1.3-7.0 points; P = 0.005). KCCQ-12 improvements were consistent across prespecified subgroups, including left ventricular ejection fraction <50% or ≥50%. More patients receiving sotagliflozin vs those receiving placebo had at least small (≥5 points) improvements in KCCQ-12 at 4 months (OR: 1.38; 95% CI: 1.06-1.80; P = 0.017). CONCLUSIONS: Sotagliflozin improved symptoms, physical limitations, and quality of life within 4 months after worsening HF, with consistent benefits across baseline demographic and clinical characteristics. (Effect of Sotagliflozin on Cardiovascular Events in Participants With Type 2 Diabetes Post Worsening Heart Failure [SOLOIST-WHF]; NCT03521934).
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Diabetes Mellitus Tipo 2 , Glicósidos , Estado de Salud , Insuficiencia Cardíaca , Inhibidores del Cotransportador de Sodio-Glucosa 2 , Humanos , Insuficiencia Cardíaca/tratamiento farmacológico , Masculino , Femenino , Glicósidos/uso terapéutico , Anciano , Inhibidores del Cotransportador de Sodio-Glucosa 2/uso terapéutico , Persona de Mediana Edad , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Diabetes Mellitus Tipo 2/complicaciones , Método Doble Ciego , Progresión de la Enfermedad , Volumen Sistólico/efectos de los fármacos , Calidad de VidaAsunto(s)
Insuficiencia Cardíaca , Inhibidores del Cotransportador de Sodio-Glucosa 2 , Humanos , Inhibidores del Cotransportador de Sodio-Glucosa 2/uso terapéutico , Inhibidores del Cotransportador de Sodio-Glucosa 2/efectos adversos , Insuficiencia Cardíaca/tratamiento farmacológico , Estado de Salud , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Diabetes Mellitus Tipo 2/complicaciones , Progresión de la EnfermedadRESUMEN
AIMS: Finerenone has been approved for treating diabetic kidney disease (DKD) with reducing cardiorenal risk. Real-world data on finerenone treatment for the management of DKD are presently lacking. This study aimed to investigate the effect of finerenone on the renal parameters of the Chinese DKD population in the real-world medical setting for the first time, especially in combination with renin-angiotensin system inhibitors (RASi) and sodium-glucose cotransporter 2 inhibitors (SGLT2i). METHODS: Forty-two DKD patients were selected and completed a 6-month finerenone treatment. Renal parameters and adverse effects were collected at every visit. RESULTS: The median urine albumin-to-creatinine ratio (UACR) was 1426.11 (755.42, 3638.23) mg/g. Among them, the proportion of patients with a UACR of 300-5000 mg/g was 76.2%, and the proportion of patients with a UACR of >5000 mg/g was 14.3%. The median estimated glomerular filtration rate (eGFR) was 54.50 (34.16, 81.73) mL/min/1.73 m2. Finerenone decreased the UACR significantly throughout the study period (p < .05). The maximal decline of UACR at month 6 was 73%. Moreover, the proportion of patients with a 30% or greater reduction in UACR was 68.42% in month 6. There was a smaller decline (9-11%) in the eGFR after initiating finerenone (p > .05). One patient each discontinued finerenone due to hyperkalemia (2.4%) and acute kidney injury (2.4%). No patient reported hypotension, breast pain, and gynecomastia. CONCLUSIONS: This study from China first demonstrated finerenone decreased UACR with manageable safety in real-world DKD treatment. A triple regimen of RASi, SGLT2i, and finerenone may be a promising treatment strategy for lowering albuminuria and reducing hyperkalemia risk in advanced DKD patients.
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Nefropatías Diabéticas , Tasa de Filtración Glomerular , Naftiridinas , Inhibidores del Cotransportador de Sodio-Glucosa 2 , Humanos , Masculino , Femenino , Nefropatías Diabéticas/tratamiento farmacológico , China , Persona de Mediana Edad , Anciano , Naftiridinas/uso terapéutico , Naftiridinas/efectos adversos , Tasa de Filtración Glomerular/efectos de los fármacos , Inhibidores del Cotransportador de Sodio-Glucosa 2/uso terapéutico , Inhibidores del Cotransportador de Sodio-Glucosa 2/efectos adversos , Albuminuria/tratamiento farmacológico , Antagonistas de Receptores de Mineralocorticoides/uso terapéutico , Antagonistas de Receptores de Mineralocorticoides/efectos adversos , Creatinina/sangre , Creatinina/orina , Inhibidores de la Enzima Convertidora de Angiotensina/uso terapéutico , Sistema Renina-Angiotensina/efectos de los fármacos , Resultado del TratamientoRESUMEN
Diabetic ketoacidosis (DKA) is a life-threatening complication of diabetes mellitus. Sodium-glucose co-transport inhibitors (SGLT-2i), a treatment for type 2 diabetes, have demonstrated a survival benefit in patients with heart failure with reduced ejection fraction (HFrEF). Many patients with HFrEF have been started on SGLT-2i and sometimes transitioned off insulin due to improved glycaemic control. SGLT-2i have demonstrated an association with DKA. Here, we present a case of simultaneous cardiogenic shock and DKA in the setting of recent transition from insulin to an SGLT-2i. DKA in conjunction with decompensated heart failure is a combination that will likely occur more frequently as SGLT-2i use becomes more widespread in patients with HFrEF, and its identification and management require special considerations. Volume status, potassium management and recognition of DKA in these patients must be approached differently than in other cases of DKA.
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Diabetes Mellitus Tipo 2 , Cetoacidosis Diabética , Choque Cardiogénico , Inhibidores del Cotransportador de Sodio-Glucosa 2 , Humanos , Cetoacidosis Diabética/complicaciones , Cetoacidosis Diabética/tratamiento farmacológico , Choque Cardiogénico/etiología , Inhibidores del Cotransportador de Sodio-Glucosa 2/uso terapéutico , Diabetes Mellitus Tipo 2/complicaciones , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Masculino , Hipoglucemiantes/uso terapéutico , Insuficiencia Cardíaca/complicaciones , Persona de Mediana Edad , Femenino , Insulina/uso terapéutico , Insulina/administración & dosificaciónRESUMEN
OBJECTIVE: Sodium-glucose co-transporter-2 inhibitors (SGLT-2i) are a new class of drugs that lower blood glucose and reduce mortality in heart failure patients with reduced ejection fraction (HFrEF). They also have antioxidant effects. The exact mechanism of SGLT-2i is unknown. This study investigated the effects of SGLT-2i on asprosin, matrix metalloproteinase (MMP), and tissue inhibitor of MMP (TIMP-1) concentrations and echocardiographic measurements of strain in the left heart chamber. PATIENTS AND METHODS: This prospective follow-up study included 56 patients with HFrEF and diabetes mellitus (DM) who did not initially receive SGLT-2 inhibitors. The control group consisted of 30 healthy individuals. Patients with HFrEF were administered either empagliflozin (n=28) or dapagliflozin (n=28) in addition to their treatment. The patient group was evaluated for left ventricular global longitudinal strain (LVGLS), left atrial (LA) strain, and LA volumes at the beginning and third month of the study. The control group had blood collected once, while the patient group had it twice: at the start of the trial, on the same day as the echocardiographic evaluation, and at the end of the third month after starting an SGLT-2i. Serum levels of asprosin, MMP-1 and TIMP-1 were assessed. RESULTS: LVGLS increased significantly in HFrEF patients at the third-month assessment compared to baseline (-8.6±2.3% vs. -9±2.5%, respectively; p<0.001), but there was no significant difference in LVEF (p=0.593). A substantial increase was observed in the left atrial ejection fraction (LAEF) compared to baseline values (36.3±9.4% vs. 42.1±8.7%, respectively; p<0.001), driven by a reduction in minimal LA volume [32.5 (19-96) ml vs. 32 (20-86) ml, respectively; p=0.018]. Compared to baseline evaluation, LA reservoir [13 (6-25) vs. 16.5 (2-26), respectively; p<0.001] and contraction strain (7.7±4.3 vs. 9.4±5.6, respectively; p=0.014) values were also enhanced at the third month. Between the baseline and the 3rd month, the patient group's LA conduit strain (p=0.122) and LA maximum volume (p=0.716) remained unchanged. Serum asprosin significantly increased (11.7±5.1 ng/mL vs. 14±9.4 ng/mL, respectively; p=0.032); however, no statistically significant alteration was detected in MMP (p=0.278) and TIMP-1 levels (p=0.401). CONCLUSIONS: SGLT-2i are associated with elevated levels of LVGLS, LAEF, LA contraction strain, and LA reservoir strain. SGLT-2i medications may improve plasma asprosin levels to boost energy metabolism, reduce oxidative stress and reactive oxygen radicals.