Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 200
Filtrar
2.
Expert Opin Drug Metab Toxicol ; 17(6): 697-705, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-33888031

RESUMO

INTRODUCTION: Recent case reports suggested that concomitant use of sodium-glucose co-transporter 2 (SGLT2) inhibitors with statins could lead to increased statin toxicity. We provide a comprehensive overview of the available pharmacological and clinical evidence on this potential drug-drug interaction (DDI). AREAS COVERED: We searched MEDLINE PubMed until November 2020 for (i) pharmacokinetic studies on SGLT2 inhibitors, statins, and their potential interaction, and (ii) case reports and clinical studies assessing the safety of concomitant use of SGLT2 inhibitors and statins. We also searched regulatory documents submitted to the United States Food and Drug Administration for unpublished data on this potential DDI. EXPERT OPINION: SGLT2 inhibitors are increasingly used for type 2 diabetes, chronic heart failure, and chronic kidney disease, and concomitant use with statins is common given the comorbidity of indications. While pharmacokinetic studies in healthy subjects showed no clinically relevant changes in statin levels during SGLT2 inhibitor co-administration, the published case reports and pharmacologic reasoning support the possibility of an interaction. Underlying mechanisms could be pharmacokinetic or pharmacodynamic, and canagliflozin appears to be the SGLT2 inhibitor with the highest interaction potential. Further research including 'real-world' pharmacoepidemiologic studies is needed to better understand the clinical significance of this DDI.


Assuntos
Canagliflozina/administração & dosagem , Inibidores de Hidroximetilglutaril-CoA Redutases/efeitos adversos , Inibidores do Transportador 2 de Sódio-Glicose/efeitos adversos , Canagliflozina/efeitos adversos , Canagliflozina/farmacologia , Diabetes Mellitus Tipo 2/tratamento farmacológico , Interações Medicamentosas , Insuficiência Cardíaca/tratamento farmacológico , Humanos , Inibidores de Hidroximetilglutaril-CoA Redutases/administração & dosagem , Inibidores de Hidroximetilglutaril-CoA Redutases/farmacocinética , Insuficiência Renal Crônica/tratamento farmacológico , Inibidores do Transportador 2 de Sódio-Glicose/administração & dosagem , Inibidores do Transportador 2 de Sódio-Glicose/farmacologia
3.
Cardiovasc Diabetol ; 20(1): 91, 2021 04 28.
Artigo em Inglês | MEDLINE | ID: mdl-33910574

RESUMO

BACKGROUND: To exam the associations between the use of sodium glucose co-transporter 2 inhibitor (SGLT2i) and the risk of lower limb complications, and to analyze the associated factors. METHODS: Pubmed, Medline, Embase, the Cochrane Center Register of Controlled Trials for Studies and Clinicaltrial.gov were searched from the inception to November 2020. Randomized controlled trials of SGLT2i conducted in population containing diabetic patients with reports of amputation, peripheral arterial disease (PAD) and diabetic foot (DF) events were included. Random-effect model, fixed-effect model and meta-regression analysis were accordingly used. RESULT: The numbers of SGLT2i users versus non-SGLT2i users in the analyses of amputation, PAD and DF were 40,925/33,414, 36,446/28,685 and 31,907/25,570 respectively. Compared with non-SGLT2i users, the risks of amputation and PAD were slightly increased in patients with canagliflozin treatment (amputation: OR = 1.60, 95% CI 1.04 to 2.46; PAD: OR = 1.53, 95 % CI 1.14 to 2.05). Meta-regression analyses indicated that greater weight reduction in SGLT2i users was significantly associated with the increased risks of amputation (ß = - 0.461, 95% CI - 0.726 to - 0.197), PAD (ß = - 0.359, 95% CI - 0.545 to - 0.172) and DF (ß = - 0.476, 95% CI - 0.836 to - 0.116). Lower baseline diastolic blood pressure (ß = - 0.528, 95% CI - 0.852 to - 0.205), more systolic blood pressure reduction (ß = - 0.207, 95% CI - 0.390 to - 0.023) and more diastolic blood pressure reduction (ß = - 0.312, 95% CI - 0.610 to - 0.015) were significantly associated with the increased risks of amputation, PAD and DF respectively in patients with SGLT2i treatment. CONCLUSIONS: The risks of amputation and PAD were slightly increased in patients with canagliflozin treatment. Reductions in body weight and blood pressure were associated with lower limb complications in patients with SGLT2i treatment.


Assuntos
Amputação , Canagliflozina/efeitos adversos , Diabetes Mellitus Tipo 2/tratamento farmacológico , Pé Diabético/cirurgia , Doença Arterial Periférica/cirurgia , Inibidores do Transportador 2 de Sódio-Glicose/efeitos adversos , Pressão Sanguínea/efeitos dos fármacos , Diabetes Mellitus Tipo 2/diagnóstico , Diabetes Mellitus Tipo 2/epidemiologia , Diabetes Mellitus Tipo 2/fisiopatologia , Pé Diabético/diagnóstico , Pé Diabético/epidemiologia , Pé Diabético/fisiopatologia , Humanos , Doença Arterial Periférica/diagnóstico , Doença Arterial Periférica/epidemiologia , Doença Arterial Periférica/fisiopatologia , Ensaios Clínicos Controlados Aleatórios como Assunto , Medição de Risco , Fatores de Risco , Fatores de Tempo , Resultado do Tratamento , Perda de Peso/efeitos dos fármacos
7.
Kidney Int ; 99(4): 814-816, 2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-33745548

RESUMO

The drop in glomerular filtration rate often observed in the first weeks of nephroprotective treatment, whether because of protein restriction or renin-angiotensin system blockade, can be interpreted as a marker of the relationship between the intensity of baseline glomerular anomalies and the potential treatment benefit. In this issue, Oshima et al. reported a post hoc analysis of the Canagliflozin and Renal Events in Diabetes With Established Nephropathy Clinical Evaluation (CREDENCE) study, the results of which confirm that such a relationship is also observed under sodium-glucose cotransporter 2 inhibition in diabetic patients with chronic kidney disease.


Assuntos
Diabetes Mellitus Tipo 2 , Insuficiência Renal Crônica , Inibidores do Transportador 2 de Sódio-Glicose , Canagliflozina/efeitos adversos , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/tratamento farmacológico , Taxa de Filtração Glomerular , Humanos , Insuficiência Renal Crônica/diagnóstico , Insuficiência Renal Crônica/tratamento farmacológico , Inibidores do Transportador 2 de Sódio-Glicose/efeitos adversos
8.
Circ Heart Fail ; 14(3): e007767, 2021 03.
Artigo em Inglês | MEDLINE | ID: mdl-33724883

RESUMO

BACKGROUND: The expense of clinical trials mandates new strategies to efficiently generate evidence and test novel therapies. In this context, we designed a decentralized, patient-centered randomized clinical trial leveraging mobile technologies, rather than in-person site visits, to test the efficacy of 12 weeks of canagliflozin for the treatment of heart failure, regardless of ejection fraction or diabetes status, on the reduction of heart failure symptoms. METHODS: One thousand nine hundred patients will be enrolled with a medical record-confirmed diagnosis of heart failure, stratified by reduced (≤40%) or preserved (>40%) ejection fraction and randomized 1:1 to 100 mg daily of canagliflozin or matching placebo. The primary outcome will be the 12-week change in the total symptom score of the Kansas City Cardiomyopathy Questionnaire. Secondary outcomes will be daily step count and other scales of the Kansas City Cardiomyopathy Questionnaire. RESULTS: The trial is currently enrolling, even in the era of the coronavirus disease 2019 (COVID-19) pandemic. CONCLUSIONS: CHIEF-HF (Canagliflozin: Impact on Health Status, Quality of Life and Functional Status in Heart Failure) is deploying a novel model of conducting a decentralized, patient-centered, randomized clinical trial for a new indication for canagliflozin to improve the symptoms of patients with heart failure. It can model a new method for more cost-effectively testing the efficacy of treatments using mobile technologies with patient-reported outcomes as the primary clinical end point of the trial. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT04252287.


Assuntos
Canagliflozina/uso terapêutico , Insuficiência Cardíaca/tratamento farmacológico , Inibidores do Transportador 2 de Sódio-Glicose/uso terapêutico , Telemedicina , Actigrafia/instrumentação , Canagliflozina/efeitos adversos , Método Duplo-Cego , Tolerância ao Exercício/efeitos dos fármacos , Monitores de Aptidão Física , Insuficiência Cardíaca/diagnóstico , Insuficiência Cardíaca/fisiopatologia , Humanos , Aplicativos Móveis , Qualidade de Vida , Ensaios Clínicos Controlados Aleatórios como Assunto , Recuperação de Função Fisiológica , Inibidores do Transportador 2 de Sódio-Glicose/efeitos adversos , Volume Sistólico/efeitos dos fármacos , Telemedicina/instrumentação , Fatores de Tempo , Resultado do Tratamento , Estados Unidos , Função Ventricular Esquerda/efeitos dos fármacos
9.
Diabetes Metab Syndr ; 15(1): 385-389, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33548908

RESUMO

BACKGROUND AND AIM: To assess short term (3 months) efficacy, safety, and tolerability of canagliflozin 100 mg among type 2 diabetes mellitus (T2DM) initiated during hot humid Indian summer. METHODS: A prospective, observational, multi-center study of 300 T2DM patients with inadequate glycemic control (i.e., HbA1c of ≥6.5%) with or without other antihyperglycemic agents (AHA) were enrolled in the study in the month of March. The objective of the study was to assess the efficacy that is changes in glycated hemoglobin (HbA1c), fasting plasma glucose (FPG), post-prandial plasma glucose (PPG), blood pressure (BP), lipid profile, body mass index (BMI) and safety of canagliflozin with regards to genitourinary infection, fall, diabetic keto acidosis (DKA) episodes, blood ketone and beta-hydroxybutyrate levels. All patients were initiated on canagliflozin 100 mg once daily for 12 weeks, irrespective of background medications. RESULTS: At 12 weeks, a significant reduction was observed in all the glycemic parameters,BMI, BP, total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C). However, a nonsignificant reduction in estimated glomerular filtration rate (eGFR) was observed at 12 weeks. A total of 9 adverse events were reported including 2 episodes of urinary tract infection (UTI) and 4 episodes of genital infection. The blood ketone, beta-hydroxybutyrate levels were found to be within normal limits and no episode of DKA was reported at 12 weeks. None of our patients had reported any volume depletion related adverse events viz. postural hypotension, giddiness etc. CONCLUSION: Canagliflozin 100 mg can be safely initiated in type 2 diabetes patients during hot humid Indian summer, irrespective of background medications and is effective and well tolerated.


Assuntos
Canagliflozina/administração & dosagem , Diabetes Mellitus Tipo 2/tratamento farmacológico , Temperatura Alta/efeitos adversos , Umidade/efeitos adversos , Estações do Ano , Inibidores do Transportador 2 de Sódio-Glicose/administração & dosagem , Adulto , Glicemia/efeitos dos fármacos , Glicemia/metabolismo , Canagliflozina/efeitos adversos , Diabetes Mellitus Tipo 2/epidemiologia , Método Duplo-Cego , Feminino , Taxa de Filtração Glomerular/efeitos dos fármacos , Taxa de Filtração Glomerular/fisiologia , Humanos , Hipoglicemiantes/administração & dosagem , Hipoglicemiantes/efeitos adversos , Índia/epidemiologia , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Inibidores do Transportador 2 de Sódio-Glicose/efeitos adversos , Fatores de Tempo , Resultado do Tratamento
10.
Circulation ; 143(18): 1735-1749, 2021 05 04.
Artigo em Inglês | MEDLINE | ID: mdl-33554616

RESUMO

BACKGROUND: People with type 2 diabetes and chronic kidney disease experience a high burden of hypertension, but the magnitude and consistency of blood pressure (BP) lowering with canagliflozin in this population are uncertain. Whether the effects of canagliflozin on kidney and cardiovascular outcomes vary by baseline BP or BP-lowering therapy is also unknown. METHODS: The CREDENCE trial (Canagliflozin and Renal Events in Diabetes with Established Nephropathy Clinical Evaluation) randomized people with type 2 diabetes and chronic kidney disease to canagliflozin or placebo. In a post hoc analysis, we investigated the effect of canagliflozin on systolic BP across subgroups defined by baseline systolic BP, number of BP-lowering drug classes, and history of apparent treatment-resistant hypertension (BP ≥130/80 mm Hg while receiving ≥3 classes of BP-lowering drugs, including a diuretic). We also assessed whether effects on clinical outcomes differed across these subgroups. RESULTS: The trial included 4401 participants, of whom 3361 (76.4%) had baseline systolic BP ≥130 mm Hg, and 1371 (31.2%) had resistant hypertension. By week 3, canagliflozin reduced systolic BP by 3.50 mm Hg (95% CI, -4.27 to -2.72), an effect maintained over the duration of the trial, with similar reductions across BP and BP-lowering therapy subgroups (all P interaction ≥0.05). Canagliflozin also reduced the need for initiation of additional BP-lowering agents during the trial (hazard ratio, 0.68 [95% CI, 0.61-0.75]). The effect of canagliflozin on kidney failure, doubling of serum creatinine, or death caused by kidney or cardiovascular disease (hazard ratio, 0.70 [95% CI, 0.59-0.82]) was consistent across BP and BP-lowering therapy subgroups (all P interaction ≥0.35), as were effects on other key kidney, cardiovascular, and safety outcomes. CONCLUSIONS: In people with type 2 diabetes and chronic kidney disease, canagliflozin lowers systolic BP across all BP-defined subgroups and reduces the need for additional BP-lowering agents. These findings support use of canagliflozin for end-organ protection and as an adjunct BP-lowering therapy in people with chronic kidney disease. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT02065791.


Assuntos
Canagliflozina/efeitos adversos , Diabetes Mellitus Tipo 2/induzido quimicamente , Insuficiência Renal Crônica/induzido quimicamente , Inibidores do Transportador 2 de Sódio-Glicose/uso terapêutico , Diabetes Mellitus Tipo 2/patologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Insuficiência Renal Crônica/patologia , Inibidores do Transportador 2 de Sódio-Glicose/farmacologia
11.
Cardiovasc Diabetol ; 20(1): 44, 2021 02 13.
Artigo em Inglês | MEDLINE | ID: mdl-33581737

RESUMO

BACKGROUND: Endothelial progenitor cells (EPCs) has been shown to be dysfunctional in both type 2 diabetes mellitus (T2DM) and chronic kidney disease (CKD) leading to poor regeneration of endothelium and renal perfusion. EPCs have been shown to be a robust cardiovascular disease (CVD) risk indicator. Effect of sodium glucose channel inhibitors (SGLT2i) such as Canagliflozin (CG) on a cellular biomarker such as CD34+ve progenitor cells, which may help predict CVD risk, in patients with T2DM with established CKD has not been explored. METHODS: This is a pilot study where 29 subjects taking metformin and/or Insulin were enrolled in a 16 week, double blind, randomized placebo matched trial, with a low dose 100 mg CG as the intervention group compared to matched placebo. Type 2 diabetes subjects (30-70 years old), with hemoglobin A1c (HbA1c) of 7-10%, were enrolled. CD34+ve cell number, migratory function, gene expression along with vascular parameters such as arterial stiffness, serum biochemistry pertaining to cardio-metabolic health, resting energy expenditure and body composition were measured. Data were collected at week 0, 8 and 16. A mixed model regression analysis was done and p value less than 0.05 was considered statistically significant. RESULTS: A significant expression of CXCR4 receptor with a concomittant increase in migratory function of CD34+ve cells was observed in CG treated group as compared to placebo group. Gene expression analysis of CD34+ve cells showed an increase in expression of antioxidants (superoxide dismutase 2 or SOD2, Catalase and Glutathione Peroxidase or GPX) and notable endothelial markers (PECAM1, VEGF-A, and NOS3). A significant reduction in glucose and HbA1c levels were observed along with improved systolic and diastolic blood pressure in the CG group. A significant increase in adiponectin (p = 0.006) was also noted in treatment group. Urinary exosomal protein leak in urine, examining podocyte health (podocalyxin, Wilm's tumor and nephrin) showed reduction with CG CONCLUSION: Low dose Canagliflozin has a beneficial effect on CD34+ cell function, serum biochemistry and urinary podocyte specific exosomes in type 2 diabetes.


Assuntos
Antígenos CD34/metabolismo , Glicemia/efeitos dos fármacos , Canagliflozina/uso terapêutico , Diabetes Mellitus Tipo 2/tratamento farmacológico , Células Progenitoras Endoteliais/efeitos dos fármacos , Inibidores do Transportador 2 de Sódio-Glicose/uso terapêutico , Adulto , Idoso , Biomarcadores/sangue , Glicemia/metabolismo , Canagliflozina/efeitos adversos , Células Cultivadas , Quimiotaxia/efeitos dos fármacos , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/patologia , Diabetes Mellitus Tipo 2/fisiopatologia , Método Duplo-Cego , Quimioterapia Combinada , Células Progenitoras Endoteliais/metabolismo , Células Progenitoras Endoteliais/patologia , Exossomos/efeitos dos fármacos , Exossomos/metabolismo , Feminino , Hemoglobina A Glicada/metabolismo , Humanos , Insulina/uso terapêutico , Masculino , Metformina/uso terapêutico , Pessoa de Meia-Idade , Fenótipo , Projetos Piloto , Inibidores do Transportador 2 de Sódio-Glicose/efeitos adversos , Fatores de Tempo , Resultado do Tratamento
14.
Am J Kidney Dis ; 77(1): 23-34.e1, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-32971190

RESUMO

RATIONALE & OBJECTIVE: Canagliflozin reduces the risk for cardiovascular and kidney outcomes in type 2 diabetes. This study aimed to assess the relative and absolute effects of canagliflozin on clinical outcomes across different KDIGO (Kidney Disease: Improving Global Outcomes) risk categories based on estimated glomerular filtration rate (eGFR) and urinary albumin-creatinine ratio. STUDY DESIGN: Post hoc analysis of the CANagliflozin cardioVascular Assessment Study (CANVAS) Program. SETTINGS & PARTICIPANTS: The CANVAS Program randomly assigned 10,142 participants with type 2 diabetes at high cardiovascular risk and with eGFR≥30mL/min/1.73m2 to treatment with canagliflozin or placebo. INTERVENTION(S): Canagliflozin or matching placebo. OUTCOMES: The primary outcome was a composite of cardiovascular death, nonfatal myocardial infarction, or nonfatal stroke, with a set of other cardiovascular and kidney prespecified outcomes. RESULTS: Of 10,142 participants, 10,031 (98.9%) had available baseline eGFR and urinary albumin-creatinine ratio data. The proportion of participants in low-, moderate-, high-, and very high-risk KDIGO categories was 58.6%, 25.8%, 10.6%, and 5.0%, respectively. The relative effect of canagliflozin on the primary outcome (HR, 0.86; 95% CI, 0.75-0.97) was consistent across KDIGO risk categories (P trend=0.2), with similar results for other cardiovascular and kidney outcomes. Absolute reductions in the primary outcome were greater within higher KDIGO risk categories (P trend=0.03) with a similar pattern of effect for the composite of cardiovascular death or hospitalization for heart failure (P trend=0.06) and for chronic eGFR slope (P trend = 0.04). LIMITATIONS: Predominantly a low kidney risk population, relatively few participants in higher KDIGO risk categories, and exclusion of individuals with eGFR<30mL/min/1.73m2. CONCLUSIONS: Although the relative effects of canagliflozin are similar across KDIGO risk categories, absolute risk reductions are likely greater for individuals at higher KDIGO risk. The KDIGO classification system may be able to identify individuals who might derive greater benefits for end-organ protection from treatment with canagliflozin. FUNDING: This post hoc analysis was not specifically funded. The original CANVAS Program trials were funded by Janssen Research & Development, LLC and were conducted as a collaboration between the funder, an academic steering committee, and an academic research organization, George Clinical. TRIAL REGISTRATION: The original trials of the CANVAS Program were registered at ClinicalTrials.gov with study numbers NCT01032629 and NCT01989754.


Assuntos
Albuminúria , Canagliflozina , Doenças Cardiovasculares , Diabetes Mellitus Tipo 2 , Insuficiência Renal Crônica , Risco Ajustado/métodos , Albuminúria/diagnóstico , Albuminúria/etiologia , Canagliflozina/administração & dosagem , Canagliflozina/efeitos adversos , Doenças Cardiovasculares/epidemiologia , Doenças Cardiovasculares/terapia , Creatinina/sangue , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/tratamento farmacológico , Feminino , Taxa de Filtração Glomerular/efeitos dos fármacos , Hospitalização/estatística & dados numéricos , Humanos , Masculino , Mortalidade , Insuficiência Renal Crônica/diagnóstico , Insuficiência Renal Crônica/epidemiologia , Insuficiência Renal Crônica/etiologia , Insuficiência Renal Crônica/metabolismo , Fatores de Risco , Inibidores do Transportador 2 de Sódio-Glicose/administração & dosagem , Inibidores do Transportador 2 de Sódio-Glicose/efeitos adversos
15.
Ann Pharmacother ; 55(4): 543-548, 2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-32808541

RESUMO

OBJECTIVE: To review the incidence, risk factors, prevention, and management of genital mycotic infections (GMIs) associated with sodium-glucose cotransporter 2 (SGLT2) inhibitors. DATA SOURCES: A literature search of PubMed and Reactions Weekly was performed in February 2020 with updated searches monthly through July 2020 to identify relevant data regarding SGLT2 inhibitors and GMIs. Manufacturers of each agent were contacted, and clinical practice guidelines were consulted. STUDY SELECTION AND DATA EXTRACTION: All available literature was evaluated for inclusion based on relevance to the research question, timeliness of the publication, validity, and impact on current practice. A date limit was not set; however, publications from 2010 to July 2020 were prioritized. DATA SYNTHESIS: The 3- to 4-fold increased incidence of GMIs is considered a classwide effect of SGLT2 inhibitors. Female sex and a prior history of GMIs are factors associated with the highest risk, whereas circumcised males are at the lowest risk of SGLT2 inhibitor-induced GMI. Personal hygiene advice can reduce the infection risk. When candidiasis occurs, it is often mild and responsive to treatment and often does not require discontinuation of the medication. RELEVANCE TO PATIENT CARE AND CLINICAL PRACTICE: This narrative review can assist in shared decision-making discussions with patients who may benefit from SGLT2 inhibitors and provides guidance for health care professionals managing SGLT2 inhibitor-associated GMIs. CONCLUSIONS: SGLT2 inhibitors predispose patients to developing mild GMIs. Strong consideration should be given to avoid SGLT2 inhibitors in female patients with a history of severe, recurrent infections. Preventive strategies are optimized diabetes management and personal hygiene advice.


Assuntos
Candidíase Vulvovaginal/induzido quimicamente , Candidíase Vulvovaginal/prevenção & controle , Gerenciamento Clínico , Genitália/efeitos dos fármacos , Higiene , Inibidores do Transportador 2 de Sódio-Glicose/efeitos adversos , Canagliflozina/efeitos adversos , Canagliflozina/uso terapêutico , Candidíase Vulvovaginal/epidemiologia , Diabetes Mellitus Tipo 2/tratamento farmacológico , Diabetes Mellitus Tipo 2/epidemiologia , Feminino , Genitália/microbiologia , Humanos , Hipoglicemiantes/efeitos adversos , Hipoglicemiantes/uso terapêutico , Masculino , Transportador 2 de Glucose-Sódio/metabolismo , Inibidores do Transportador 2 de Sódio-Glicose/uso terapêutico
16.
Kidney Int ; 99(4): 999-1009, 2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-33316282

RESUMO

Canagliflozin slows the progression of chronic kidney disease in patients with type 2 diabetes and induces a reversible acute drop in estimated glomerular filtration rate (eGFR), believed to be a hemodynamic effect. Predictors of the initial drop and its association with long-term eGFR trajectories and safety outcomes are unknown. To assess this, we performed a post-hoc analysis of 4289 participants in the CREDENCE trial with type 2 diabetes and chronic kidney disease equally split into treatment and placebo groups who had eGFR measured at both baseline and week three. The eGFR was categorized at week three as greater than a 10% decline; between 0 and 10% decline; and no decline. Long-term eGFR trajectories and safety outcomes were estimated in each category of acute eGFR change by linear mixed effects models and Cox regression after adjustment for baseline characteristics and medications use. Significantly more participants in the canagliflozin (45%) compared to the placebo (21%) group experienced an acute drop in eGFR over 10%. An over 30% drop occurred infrequently (4% of participants with canagliflozin and 2% with placebo). The odds ratio for a drop in eGFR over 10% with canagliflozin compared to placebo was significant at 3.03 (95% confidence interval 2.65, 3.47). Following the initial drop in eGFR, multivariable adjusted long-term eGFR trajectories, as well as overall and kidney safety profiles, in those treated with canagliflozin were similar across eGFR decline categories. Thus, although acute drops in eGFR over 10% occurred in nearly half of all participants following initiation of canagliflozin, the clinical benefit of canagliflozin was observed regardless. Additionally, safety outcomes were similar among subgroups of acute eGFR drop.


Assuntos
Diabetes Mellitus Tipo 2 , Insuficiência Renal Crônica , Inibidores do Transportador 2 de Sódio-Glicose , Canagliflozina/efeitos adversos , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/diagnóstico , Diabetes Mellitus Tipo 2/tratamento farmacológico , Taxa de Filtração Glomerular , Humanos , Insuficiência Renal Crônica/diagnóstico , Inibidores do Transportador 2 de Sódio-Glicose/efeitos adversos
17.
Am Heart J ; 233: 141-148, 2021 03.
Artigo em Inglês | MEDLINE | ID: mdl-33358942

RESUMO

We aimed to assess the efficacy and safety of canagliflozin in patients with type 2 diabetes and nephropathy according to prior history of heart failure in the Canagliflozin and Renal Events in Diabetes With Established Nephropathy Clinical Evaluation (CREDENCE) trial. We found that participants with a prior history of heart failure at baseline (15%) were more likely to be older, female, white, have a history of atherosclerotic cardiovascular disease, and use diuretics and beta blockers (all P < .001), and that, compared with placebo, canagliflozin safely reduced renal and cardiovascular events with consistent effects in patients with and without a prior history of heart failure (all efficacy P interaction >.150). These results support the efficacy and safety of canagliflozin in patients with type 2 diabetes and nephropathy regardless of prior history of heart failure.


Assuntos
Canagliflozina/uso terapêutico , Diabetes Mellitus Tipo 2/tratamento farmacológico , Insuficiência Cardíaca/complicações , Insuficiência Renal Crônica/tratamento farmacológico , Inibidores do Transportador 2 de Sódio-Glicose/uso terapêutico , Antagonistas Adrenérgicos beta/uso terapêutico , Fatores Etários , Idoso , Canagliflozina/efeitos adversos , Doenças Cardiovasculares/prevenção & controle , Diuréticos/uso terapêutico , Método Duplo-Cego , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Placebos/uso terapêutico , Fatores Sexuais , Inibidores do Transportador 2 de Sódio-Glicose/efeitos adversos
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...