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1.
Diabetes Obes Metab ; 23(1): 263-269, 2021 01.
Artículo en Inglés | MEDLINE | ID: mdl-32991065

RESUMEN

Sodium-glucose co-transporter-2 (SGLT2) inhibitors are widely prescribed in people with type 2 diabetes. We aimed to investigate whether SGLT2 inhibitor prescription is associated with COVID-19, when compared with an active comparator. We performed a propensity-score-matched cohort study with active comparators and a negative control outcome in a large UK-based primary care dataset. Participants prescribed SGLT2 inhibitors (n = 9948) and a comparator group prescribed dipeptidyl peptidase-4 (DPP-4) inhibitors (n = 14 917) were followed up from January 30 to July 27, 2020. The primary outcome was confirmed or clinically suspected COVID-19. The incidence rate of COVID-19 was 19.7/1000 person-years among users of SGLT2 inhibitors and 24.7/1000 person-years among propensity-score-matched users of DPP-4 inhibitors. The adjusted hazard ratio was 0.92 (95% confidence interval 0.66 to 1.29), and there was no evidence of residual confounding in the negative control analysis. We did not observe an increased risk of COVID-19 in primary care amongst those prescribed SGLT2 inhibitors compared to DPP-4 inhibitors, suggesting that clinicians may safely use these agents in the everyday care of people with type 2 diabetes during the COVID-19 pandemic.


Asunto(s)
/epidemiología , Susceptibilidad a Enfermedades , Inhibidores del Cotransportador de Sodio-Glucosa 2/efectos adversos , Anciano , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Femenino , Humanos , Masculino , Persona de Mediana Edad , Pandemias , Puntaje de Propensión , Estudios Retrospectivos , Inhibidores del Cotransportador de Sodio-Glucosa 2/uso terapéutico
3.
Lancet Diabetes Endocrinol ; 8(12): 949-959, 2020 12.
Artículo en Inglés | MEDLINE | ID: mdl-33217335

RESUMEN

BACKGROUND: Patients with type 2 diabetes and atherosclerotic cardiovascular disease are at high clinical risk. We assessed the effect of the sodium-glucose co-transporter-2 inhibitor, empagliflozin, on total cardiovascular events and admissions to hospital in the EMPA-REG OUTCOME trial. METHODS: The EMPA-REG OUTCOME trial was a randomised, double-blind, non-inferiority trial of patients (aged ≥18 years) with type 2 diabetes and atherosclerotic cardiovascular disease done between August, 2010, and April, 2015. Participants were randomly assigned (1:1:1) to empagliflozin 10 mg or 25 mg, or placebo. The primary outcome was major adverse cardiovascular events: a composite of cardiovascular death, non-fatal stroke, or non-fatal myocardial infarction. As prespecified, the effects of pooled empagliflozin versus placebo were assessed on total (first plus recurrent) events of major adverse cardiovascular events, fatal or non-fatal myocardial infarction, fatal or non-fatal stroke, and admission to hospital for heart failure. We also did post-hoc analyses on additional cardiovascular and admission to hospital outcomes. We used statistical models that preserve randomisation and account for correlation of recurrent events, including negative binomial regression, as prespecified for the primary analyses. The EMPA-REG OUTCOME trial is registered with ClinicalTrials.gov, NCT01131676, and is closed to accrual. FINDINGS: In the EMPA-REG OUTCOME trial, 7020 patients were randomly assigned and treated with empagliflozin 10 mg (n=2345), empagliflozin 25 mg (n=2342), or placebo (n=2333) and followed up for a median of 3·2 years (IQR 2·2 to 3·6) in the pooled empagliflozin group and 3·1 years (2·2 to 3·5) in the placebo group. Analysing total (first plus recurrent) events, empagliflozin versus placebo reduced the risk of major adverse cardiovascular events (rate ratio [RR] 0·78 [95% CI 0·67 to 0·91]; p=0·0020; 12·88 [95% CI 3·74 to 22·02] events prevented per 1000 patient-years); fatal or non-fatal myocardial infarction (0·79 [0·62 to 0·998]; p=0·049; 4·97 [-0·68 to 10·61] events prevented per 1000 patient-years); the composite of fatal or non-fatal myocardial infarction, or coronary revascularisation (0·80 [0·67 to 0·95]; p=0·012; 11·65 [1·25 to 22·05] events prevented per 1000 patient-years); admission to hospital for heart failure (0·58 [0·42 to 0·81]; p=0·0012; 9·67 [3·07 to 16·28] events prevented per 1000 patient-years); and all-cause admission to hospital (0·83 [0·76 to 0·91]; p<0·0001; 50·41 [26·20 to 74·63] events prevented per 1000 patient-years). For outcomes significantly reduced with empagliflozin, risk reductions were numerically larger for total events than for first events. Total fatal or non-fatal stroke was not significantly different between treatment groups (RR 1·10 [95% CI 0·82 to 1·49]; p=0·52). INTERPRETATION: Empagliflozin reduced the total burden of cardiovascular complications and all-cause admission to hospital in patients with type 2 diabetes and atherosclerotic cardiovascular disease. FUNDING: The Boehringer Ingelheim and Lilly Alliance.


Asunto(s)
Aterosclerosis/prevención & control , Compuestos de Bencidrilo/uso terapéutico , Biomarcadores/análisis , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Glucósidos/uso terapéutico , Hospitalización/estadística & datos numéricos , Inhibidores del Cotransportador de Sodio-Glucosa 2/uso terapéutico , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Aterosclerosis/epidemiología , Compuestos de Bencidrilo/efectos adversos , Glucemia/análisis , Método Doble Ciego , Estudios de Equivalencia como Asunto , Femenino , Estudios de Seguimiento , Glucósidos/efectos adversos , Hemoglobina A Glucada/análisis , Humanos , Incidencia , Masculino , Persona de Mediana Edad , Pronóstico , Factores de Riesgo , Inhibidores del Cotransportador de Sodio-Glucosa 2/efectos adversos , Estados Unidos/epidemiología , Adulto Joven
6.
Drug Saf ; 43(12): 1211-1221, 2020 12.
Artículo en Inglés | MEDLINE | ID: mdl-33095409

RESUMEN

Sodium-glucose cotransporter 2 (SGLT2) inhibitors are a major advance in the fields of diabetology, nephrology, and cardiology. The cardiovascular and renal benefits of SGLT2 inhibitors are likely largely independent of their glycaemic effects, and this understanding is central to the use of these agents in the high-risk population of people with type 2 diabetes and chronic kidney disease. There are a number of potential safety issues associated with the use of SGLT2 inhibitors. These include the rare but serious risks of diabetic ketoacidosis and necrotising fasciitis of the perineum. The data regarding a possibly increased risk of lower limb amputation and fracture with SGLT2 inhibitor therapy are conflicting. This article aims to explore the potential safety issues associated with the use of SGLT2 inhibitors, with a particular focus on the safety of these drugs in people with type 2 diabetes and chronic kidney disease. We discuss strategies that clinicians can implement to minimise the risk of adverse effects including diabetic ketoacidosis and volume depletion. Risk mitigation strategies with respect to SGLT2 inhibitor-associated diabetic ketoacidosis are of particular importance during the current coronavirus disease 2019 (COVID-19) pandemic.


Asunto(s)
Diabetes Mellitus Tipo 2/tratamiento farmacológico , Cetoacidosis Diabética/inducido químicamente , Fascitis Necrotizante/inducido químicamente , Hipovolemia/inducido químicamente , Insuficiencia Renal Crónica/complicaciones , Inhibidores del Cotransportador de Sodio-Glucosa 2/efectos adversos , Lesión Renal Aguda/inducido químicamente , Amputación/estadística & datos numéricos , Diabetes Mellitus Tipo 2/complicaciones , Diabetes Mellitus Tipo 2/metabolismo , Gangrena de Fournier/inducido químicamente , Fracturas Óseas/inducido químicamente , Humanos , Hipoglucemia/inducido químicamente , Educación del Paciente como Asunto , Perineo , Infecciones del Sistema Genital/inducido químicamente , Factores de Riesgo , Infecciones Urinarias/inducido químicamente
8.
Ann Intern Med ; 173(8): JC40, 2020 10 20.
Artículo en Inglés | MEDLINE | ID: mdl-33075260

RESUMEN

SOURCE CITATION: Liu J, Li L, Li S, et al. Sodium-glucose co-transporter-2 inhibitors and the risk of diabetic ketoacidosis in patients with type 2 diabetes: a systematic review and meta-analysis of randomized controlled trials. Diabetes Obes Metab. 2020;22:1619-27. 32364674.


Asunto(s)
Diabetes Mellitus Tipo 2 , Cetoacidosis Diabética , Inhibidores del Cotransportador de Sodio-Glucosa 2 , Simportadores , Diabetes Mellitus Tipo 2/complicaciones , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Cetoacidosis Diabética/inducido químicamente , Glucosa , Humanos , Hipoglucemiantes/efectos adversos , Ensayos Clínicos Controlados Aleatorios como Asunto , Sodio , Inhibidores del Cotransportador de Sodio-Glucosa 2/efectos adversos
9.
Postgrad Med ; 132(8): 697-701, 2020 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-33016178

RESUMEN

BACKGROUND: Type 2 diabetes mellitus (T2DM) in postmenopausal women is associated with a high incidence of urogenital infections, which negatively impact the quality of life and increase morbidity, mortality, and health-care costs. Glucosuria is a known risk factor for these infections; therefore, it is of interest to determine if increased glucosuria secondary to sodium-glucose cotransporter-2 inhibitors (SGLT2in) impacts the incidence and severity of urogenital infections in postmenopausal women with T2DM. METHODS: The study was conducted at Gaffrée Guinle University Hospital on two groups of postmenopausal women with T2DM: with and without SGLT2in therapy (n = 80 in each group). Medical records and laboratory parameters (urinary dipstick test and culture; blood glucose, glycosylated hemoglobin, and creatinine; cervical cytologic study) of all subjects were carefully assessed at baseline and thrice during the 12-month study period. RESULTS: We observed a significant incidence of vulvovaginitis (relative risk [RR], 2.37; 95% confidence interval [CI], 1.10-5.10; P = 0.03) and asymptomatic bacteriuria (RR, 2.47; 95% CI, 1.09-5.60; P = 0.03), but not of urinary tract infections (RR, 2.08; 95% CI, 0.74-5.81; P = 0.16), secondary to SGLT2in therapy. Genital infection was severe enough to warrant treatment discontinuation in 57.89% of patients in group 1. All urinary tract infections were of mild intensity with a good response to antibiotic therapy. CONCLUSION: Glucosuria induced by SGLT2in therapy may lead to a high incidence of urogenital infections in postmenopausal women with T2DM and can be considered a risk factor for these infections.


Asunto(s)
Diabetes Mellitus Tipo 2/tratamiento farmacológico , Glucosuria/inducido químicamente , Glucosuria/complicaciones , Posmenopausia , Inhibidores del Cotransportador de Sodio-Glucosa 2/efectos adversos , Infecciones Urinarias/etiología , Anciano , Antibacterianos/uso terapéutico , Bacteriuria/etiología , Glucemia , Estudios de Casos y Controles , Creatinina/sangre , Femenino , Hemoglobina A Glucada , Humanos , Incidencia , Estudios Longitudinales , Persona de Mediana Edad , Estudios Prospectivos , Factores de Riesgo , Índice de Severidad de la Enfermedad , Inhibidores del Cotransportador de Sodio-Glucosa 2/uso terapéutico , Infecciones Urinarias/tratamiento farmacológico , Vulvovaginitis/etiología
11.
J Coll Physicians Surg Pak ; 30(10): 110-111, 2020 10.
Artículo en Inglés | MEDLINE | ID: mdl-33115581

RESUMEN

Sodium glucose cotransporter 2 (SGLT2) inhibitors are among the new generation oral anti-diabetic drugs that have started to be used in the treatment of type 2 diabetes mellitus. Although these drugs are highly beneficial, life-threatening side effects such as euglycemic diabetic ketoacidosis (eDKA) are reported with their use. In eDKA, metabolic acidosis and anion gap appear in blood gases and serum glucose in less than 200 mg/dl.This can delay diagnosis and treatment. In our case, a 42-year female presented to the Emergency Room with nausea and vomiting. It was observed that the patient had been using empagliflozin for a year. Her blood gas analyses and laboratory tests showed metabolic acidosis and ketosis. The patient was initially suspected to be a case of coronavirus disease-2019 (COVID-19) complicating the course of diabetes, finally it was diagnosed as a case of eDKA due to empagliflozin use. We noticed that during the current pandemic, some other diagnoses can be missed or their diagnosis can be delayed. Key Words: Euglycemic diabetic ketoacidosis, Empagliflozin, COVID-19, Diabetes mellitus.


Asunto(s)
Compuestos de Bencidrilo/efectos adversos , Cetoacidosis Diabética/inducido químicamente , Glucósidos/efectos adversos , Inhibidores del Cotransportador de Sodio-Glucosa 2/efectos adversos , Adulto , Betacoronavirus , Infecciones por Coronavirus/diagnóstico , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Diagnóstico Diferencial , Femenino , Humanos , Pandemias , Neumonía Viral/diagnóstico
12.
Diabetes Res Clin Pract ; 169: 108465, 2020 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-32971151

RESUMEN

Fasting from dawn to sunset, during the holy month of Ramadan, constitutes one of the five main pillars in Islam and is observed by the majority of Muslims. Owing to important physiological changes, Ramadan fasting holds a crucial place in the context of diabetes management. Approximately one-fifth of the world's Muslim population resides in the Middle East and Africa (MEA) region. To discuss the challenges and management of diabetes during Ramadan fasting in the MEA region, a panel of 12 experts in the field of diabetes from across the MEA region attended two expert committee meetings held in Dubai. The key point of discussion was the safety and efficacy of the use of sodium-glucose co-transporter 2 inhibitors (SGLT2i) during Ramadan, based on outcomes of the recent clinical trials with SGLT2i. This is the first consensus recommendation on the management of diabetes with SGLT2i across the MEA region during Ramadan. The document summarizes expert views and opinions on the current management of diabetes with SGLT2i during Ramadan and aims to enhance the current knowledge and understanding on the issue of diabetes management during Ramadan. This will aid the physicians of the MEA region with appropriate decision-making for their patients during Ramadan.


Asunto(s)
Diabetes Mellitus/tratamiento farmacológico , Ayuno , Islamismo , Guías de Práctica Clínica como Asunto , Inhibidores del Cotransportador de Sodio-Glucosa 2/uso terapéutico , África , Consenso , Deshidratación/epidemiología , Cetoacidosis Diabética/epidemiología , Femenino , Humanos , Hiperglucemia/epidemiología , Hipoglucemia/epidemiología , Masculino , Medio Oriente , Factores de Riesgo , Inhibidores del Cotransportador de Sodio-Glucosa 2/efectos adversos , Infecciones Urinarias/epidemiología
13.
Lancet ; 396(10254): 819-829, 2020 09 19.
Artículo en Inglés | MEDLINE | ID: mdl-32877652

RESUMEN

BACKGROUND: Both DAPA-HF (assessing dapagliflozin) and EMPEROR-Reduced (assessing empagliflozin) trials showed that sodium-glucose co-transporter-2 (SGLT2) inhibition reduced the combined risk of cardiovascular death or hospitalisation for heart failure in patients with heart failure with reduced ejection fraction (HFrEF) with or without diabetes. However, neither trial was powered to assess effects on cardiovascular death or all-cause death or to characterise effects in clinically important subgroups. Using study-level published data from DAPA-HF and patient-level data from EMPEROR-Reduced, we aimed to estimate the effect of SGLT2 inhibition on fatal and non-fatal heart failure events and renal outcomes in all randomly assigned patients with HFrEF and in relevant subgroups from DAPA-HF and EMPEROR-Reduced trials. METHODS: We did a prespecified meta-analysis of the two single large-scale trials assessing the effects of SGLT2 inhibitors on cardiovascular outcomes in patients with HFrEF with or without diabetes: DAPA-HF (assessing dapagliflozin) and EMPEROR-Reduced (assessing empagliflozin). The primary endpoint was time to all-cause death. Additionally, we assessed the effects of treatment in prespecified subgroups on the combined risk of cardiovascular death or hospitalisation for heart failure. These subgroups were based on type 2 diabetes status, age, sex, angiotensin receptor neprilysin inhibitor (ARNI) treatment, New York Heart Association (NYHA) functional class, race, history of hospitalisation for heart failure, estimated glomerular filtration rate (eGFR), body-mass index, and region (post-hoc). We used hazard ratios (HRs) derived from Cox proportional hazard models for time-to-first event endpoints and Cochran's Q test for treatment interactions; the analysis of recurrent events was based on rate ratios derived from the Lin-Wei-Yang-Ying model. FINDINGS: Among 8474 patients combined from both trials, the estimated treatment effect was a 13% reduction in all-cause death (pooled HR 0·87, 95% CI 0·77-0·98; p=0·018) and 14% reduction in cardiovascular death (0·86, 0·76-0·98; p=0·027). SGLT2 inhibition was accompanied by a 26% relative reduction in the combined risk of cardiovascular death or first hospitalisation for heart failure (0·74, 0·68-0·82; p<0·0001), and by a 25% decrease in the composite of recurrent hospitalisations for heart failure or cardiovascular death (0·75, 0·68-0·84; p<0·0001). The risk of the composite renal endpoint was also reduced (0·62, 0·43-0·90; p=0·013). All tests for heterogeneity of effect size between trials were not significant. The pooled treatment effects showed consistent benefits for subgroups based on age, sex, diabetes, treatment with an ARNI and baseline eGFR, but suggested treatment-by-subgroup interactions for subgroups based on NYHA functional class and race. INTERPRETATION: The effects of empagliflozin and dapagliflozin on hospitalisations for heart failure were consistent in the two independent trials and suggest that these agents also improve renal outcomes and reduce all-cause and cardiovascular death in patients with HFrEF. FUNDING: Boehringer Ingelheim.


Asunto(s)
Compuestos de Bencidrilo/efectos adversos , Glucósidos/efectos adversos , Insuficiencia Cardíaca/tratamiento farmacológico , Inhibidores del Cotransportador de Sodio-Glucosa 2/efectos adversos , Volumen Sistólico/efectos de los fármacos , Anciano , Antagonistas de Receptores de Angiotensina/uso terapéutico , Compuestos de Bencidrilo/uso terapéutico , Índice de Masa Corporal , Estudios de Casos y Controles , Causas de Muerte/tendencias , Ensayos Clínicos como Asunto , Muerte , Diabetes Mellitus Tipo 2/complicaciones , Quimioterapia Combinada , Femenino , Tasa de Filtración Glomerular/efectos de los fármacos , Tasa de Filtración Glomerular/fisiología , Glucósidos/uso terapéutico , Insuficiencia Cardíaca/clasificación , Insuficiencia Cardíaca/fisiopatología , Hospitalización/estadística & datos numéricos , Humanos , Masculino , Persona de Mediana Edad , Neprilisina/antagonistas & inhibidores , Evaluación del Resultado de la Atención al Paciente , Inhibidores del Cotransportador de Sodio-Glucosa 2/uso terapéutico
14.
N Engl J Med ; 383(15): 1425-1435, 2020 10 08.
Artículo en Inglés | MEDLINE | ID: mdl-32966714

RESUMEN

BACKGROUND: The cardiovascular effects of ertugliflozin, an inhibitor of sodium-glucose cotransporter 2, have not been established. METHODS: In a multicenter, double-blind trial, we randomly assigned patients with type 2 diabetes and atherosclerotic cardiovascular disease to receive 5 mg or 15 mg of ertugliflozin or placebo once daily. With the data from the two ertugliflozin dose groups pooled for analysis, the primary objective was to show the noninferiority of ertugliflozin to placebo with respect to the primary outcome, major adverse cardiovascular events (a composite of death from cardiovascular causes, nonfatal myocardial infarction, or nonfatal stroke). The noninferiority margin was 1.3 (upper boundary of a 95.6% confidence interval for the hazard ratio [ertugliflozin vs. placebo] for major adverse cardiovascular events). The first key secondary outcome was a composite of death from cardiovascular causes or hospitalization for heart failure. RESULTS: A total of 8246 patients underwent randomization and were followed for a mean of 3.5 years. Among 8238 patients who received at least one dose of ertugliflozin or placebo, a major adverse cardiovascular event occurred in 653 of 5493 patients (11.9%) in the ertugliflozin group and in 327 of 2745 patients (11.9%) in the placebo group (hazard ratio, 0.97; 95.6% confidence interval [CI], 0.85 to 1.11; P<0.001 for noninferiority). Death from cardiovascular causes or hospitalization for heart failure occurred in 444 of 5499 patients (8.1%) in the ertugliflozin group and in 250 of 2747 patients (9.1%) in the placebo group (hazard ratio, 0.88; 95.8% CI, 0.75 to 1.03; P = 0.11 for superiority). The hazard ratio for death from cardiovascular causes was 0.92 (95.8% CI, 0.77 to 1.11), and the hazard ratio for death from renal causes, renal replacement therapy, or doubling of the serum creatinine level was 0.81 (95.8% CI, 0.63 to 1.04). Amputations were performed in 54 patients (2.0%) who received the 5-mg dose of ertugliflozin and in 57 patients (2.1%) who received the 15-mg dose, as compared with 45 patients (1.6%) who received placebo. CONCLUSIONS: Among patients with type 2 diabetes and atherosclerotic cardiovascular disease, ertugliflozin was noninferior to placebo with respect to major adverse cardiovascular events. (Funded by Merck Sharp & Dohme and Pfizer; VERTIS CV ClinicalTrials.gov number, NCT01986881.).


Asunto(s)
Aterosclerosis/tratamiento farmacológico , Compuestos Bicíclicos Heterocíclicos con Puentes/uso terapéutico , Enfermedades Cardiovasculares/epidemiología , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Hospitalización/estadística & datos numéricos , Inhibidores del Cotransportador de Sodio-Glucosa 2/uso terapéutico , Anciano , Aterosclerosis/complicaciones , Compuestos Bicíclicos Heterocíclicos con Puentes/administración & dosificación , Compuestos Bicíclicos Heterocíclicos con Puentes/efectos adversos , Enfermedades Cardiovasculares/mortalidad , Diabetes Mellitus Tipo 2/complicaciones , Nefropatías Diabéticas/complicaciones , Método Doble Ciego , Femenino , Humanos , Masculino , Persona de Mediana Edad , Placebos/uso terapéutico , Inhibidores del Cotransportador de Sodio-Glucosa 2/administración & dosificación , Inhibidores del Cotransportador de Sodio-Glucosa 2/efectos adversos
16.
N Engl J Med ; 383(15): 1413-1424, 2020 10 08.
Artículo en Inglés | MEDLINE | ID: mdl-32865377

RESUMEN

BACKGROUND: Sodium-glucose cotransporter 2 (SGLT2) inhibitors reduce the risk of hospitalization for heart failure in patients regardless of the presence or absence of diabetes. More evidence is needed regarding the effects of these drugs in patients across the broad spectrum of heart failure, including those with a markedly reduced ejection fraction. METHODS: In this double-blind trial, we randomly assigned 3730 patients with class II, III, or IV heart failure and an ejection fraction of 40% or less to receive empagliflozin (10 mg once daily) or placebo, in addition to recommended therapy. The primary outcome was a composite of cardiovascular death or hospitalization for worsening heart failure. RESULTS: During a median of 16 months, a primary outcome event occurred in 361 of 1863 patients (19.4%) in the empagliflozin group and in 462 of 1867 patients (24.7%) in the placebo group (hazard ratio for cardiovascular death or hospitalization for heart failure, 0.75; 95% confidence interval [CI], 0.65 to 0.86; P<0.001). The effect of empagliflozin on the primary outcome was consistent in patients regardless of the presence or absence of diabetes. The total number of hospitalizations for heart failure was lower in the empagliflozin group than in the placebo group (hazard ratio, 0.70; 95% CI, 0.58 to 0.85; P<0.001). The annual rate of decline in the estimated glomerular filtration rate was slower in the empagliflozin group than in the placebo group (-0.55 vs. -2.28 ml per minute per 1.73 m2 of body-surface area per year, P<0.001), and empagliflozin-treated patients had a lower risk of serious renal outcomes. Uncomplicated genital tract infection was reported more frequently with empagliflozin. CONCLUSIONS: Among patients receiving recommended therapy for heart failure, those in the empagliflozin group had a lower risk of cardiovascular death or hospitalization for heart failure than those in the placebo group, regardless of the presence or absence of diabetes. (Funded by Boehringer Ingelheim and Eli Lilly; EMPEROR-Reduced ClinicalTrials.gov number, NCT03057977.).


Asunto(s)
Compuestos de Bencidrilo/uso terapéutico , Enfermedades Cardiovasculares/prevención & control , Glucósidos/uso terapéutico , Insuficiencia Cardíaca/tratamiento farmacológico , Hospitalización/estadística & datos numéricos , Inhibidores del Cotransportador de Sodio-Glucosa 2/uso terapéutico , Anciano , Compuestos de Bencidrilo/efectos adversos , Enfermedades Cardiovasculares/mortalidad , Diabetes Mellitus Tipo 2/complicaciones , Progresión de la Enfermedad , Método Doble Ciego , Femenino , Tasa de Filtración Glomerular/efectos de los fármacos , Glucósidos/efectos adversos , Insuficiencia Cardíaca/complicaciones , Insuficiencia Cardíaca/fisiopatología , Humanos , Masculino , Persona de Mediana Edad , Modelos de Riesgos Proporcionales , Insuficiencia Renal Crónica/complicaciones , Inhibidores del Cotransportador de Sodio-Glucosa 2/efectos adversos , Volumen Sistólico
17.
N Engl J Med ; 383(15): 1436-1446, 2020 10 08.
Artículo en Inglés | MEDLINE | ID: mdl-32970396

RESUMEN

BACKGROUND: Patients with chronic kidney disease have a high risk of adverse kidney and cardiovascular outcomes. The effect of dapagliflozin in patients with chronic kidney disease, with or without type 2 diabetes, is not known. METHODS: We randomly assigned 4304 participants with an estimated glomerular filtration rate (GFR) of 25 to 75 ml per minute per 1.73 m2 of body-surface area and a urinary albumin-to-creatinine ratio (with albumin measured in milligrams and creatinine measured in grams) of 200 to 5000 to receive dapagliflozin (10 mg once daily) or placebo. The primary outcome was a composite of a sustained decline in the estimated GFR of at least 50%, end-stage kidney disease, or death from renal or cardiovascular causes. RESULTS: The independent data monitoring committee recommended stopping the trial because of efficacy. Over a median of 2.4 years, a primary outcome event occurred in 197 of 2152 participants (9.2%) in the dapagliflozin group and 312 of 2152 participants (14.5%) in the placebo group (hazard ratio, 0.61; 95% confidence interval [CI], 0.51 to 0.72; P<0.001; number needed to treat to prevent one primary outcome event, 19 [95% CI, 15 to 27]). The hazard ratio for the composite of a sustained decline in the estimated GFR of at least 50%, end-stage kidney disease, or death from renal causes was 0.56 (95% CI, 0.45 to 0.68; P<0.001), and the hazard ratio for the composite of death from cardiovascular causes or hospitalization for heart failure was 0.71 (95% CI, 0.55 to 0.92; P = 0.009). Death occurred in 101 participants (4.7%) in the dapagliflozin group and 146 participants (6.8%) in the placebo group (hazard ratio, 0.69; 95% CI, 0.53 to 0.88; P = 0.004). The effects of dapagliflozin were similar in participants with type 2 diabetes and in those without type 2 diabetes. The known safety profile of dapagliflozin was confirmed. CONCLUSIONS: Among patients with chronic kidney disease, regardless of the presence or absence of diabetes, the risk of a composite of a sustained decline in the estimated GFR of at least 50%, end-stage kidney disease, or death from renal or cardiovascular causes was significantly lower with dapagliflozin than with placebo. (Funded by AstraZeneca; DAPA-CKD ClinicalTrials.gov number, NCT03036150.).


Asunto(s)
Compuestos de Bencidrilo/uso terapéutico , Tasa de Filtración Glomerular/efectos de los fármacos , Glucósidos/uso terapéutico , Insuficiencia Renal Crónica/tratamiento farmacológico , Inhibidores del Cotransportador de Sodio-Glucosa 2/uso terapéutico , Anciano , Compuestos de Bencidrilo/efectos adversos , Compuestos de Bencidrilo/farmacología , Enfermedades Cardiovasculares/etiología , Enfermedades Cardiovasculares/mortalidad , Enfermedades Cardiovasculares/prevención & control , Diabetes Mellitus Tipo 2/complicaciones , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Nefropatías Diabéticas/tratamiento farmacológico , Femenino , Glucósidos/efectos adversos , Glucósidos/farmacología , Humanos , Estimación de Kaplan-Meier , Fallo Renal Crónico/mortalidad , Masculino , Persona de Mediana Edad , Análisis de Regresión , Insuficiencia Renal Crónica/complicaciones , Inhibidores del Cotransportador de Sodio-Glucosa 2/efectos adversos , Inhibidores del Cotransportador de Sodio-Glucosa 2/farmacología
18.
Expert Opin Pharmacother ; 21(17): 2101-2114, 2020 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-32990096

RESUMEN

INTRODUCTION: Saxagliptin, a member of the dipeptidyl peptidase-4 inhibitor (DPP-4i) class of drugs, was approved by the FDA for the treatment of type 2 diabetes (T2D) in 2009, and has been in clinical use for more than a decade. Since the drug was first launched, much real-world evidence has also been accumulated. The efficacy and safety of saxagliptin, especially its cardiovascular safety, are of particular interest. AREAS COVERED: This review provides an overview of the safety and efficacy of saxagliptin based on observational studies, pharmacovigilance, and meta-analyses. In addition, with the findings of recent cardiovascular outcome trials (CVOTs), the authors discuss, herein, the efficacious use of saxagliptin. EXPERT OPINION: Saxagliptin exhibits a moderate glucose-lowering effect and is well tolerated by patients with T2D. SAVOR-TIMI 53, a CVOT of saxagliptin, reported neutral effects of saxagliptin in respect of the cardiovascular outcomes, but did raise a concern about the risk of heart failure. Conversely, recent CVOTs on sodium-glucose co-transporter-2 inhibitors (SGLT2i) have shown a favorably reduced risk of heart failure with these drugs. Also, DPP-4is decrease the serum glucagon level, whereas the SGLT2is increase it. Given the characteristics of the two classes of drugs, combined therapy with the two might be a promising option.


Asunto(s)
Adamantano/análogos & derivados , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Dipéptidos/uso terapéutico , Inhibidores de la Dipeptidil-Peptidasa IV/uso terapéutico , Hipoglucemiantes/uso terapéutico , Adamantano/administración & dosificación , Adamantano/efectos adversos , Adamantano/uso terapéutico , Glucemia/análisis , Diabetes Mellitus Tipo 2/sangre , Dipéptidos/administración & dosificación , Dipéptidos/efectos adversos , Inhibidores de la Dipeptidil-Peptidasa IV/administración & dosificación , Inhibidores de la Dipeptidil-Peptidasa IV/efectos adversos , Insuficiencia Cardíaca/inducido químicamente , Humanos , Hipoglucemia/inducido químicamente , Hipoglucemiantes/administración & dosificación , Hipoglucemiantes/efectos adversos , Ensayos Clínicos Controlados Aleatorios como Asunto , Inhibidores del Cotransportador de Sodio-Glucosa 2/administración & dosificación , Inhibidores del Cotransportador de Sodio-Glucosa 2/efectos adversos , Inhibidores del Cotransportador de Sodio-Glucosa 2/uso terapéutico , Resultado del Tratamiento
19.
Actual. osteol ; 16(2): [95]-[103], mayo.-ago. 2020. ilus, graf, tab
Artículo en Inglés | LILACS | ID: biblio-1129692

RESUMEN

Introduction. Diabetes is a chronic disease associated with important comorbidities. Type 2 diabetes (T2DM) is associated with a three times increased risk of hip fracture but reports describing potential associations with vertebral fractures (VF) are contradictory. Our objective was to evaluate the factors involved in the prevalent VF in women with and without T2DM. Materials and methods. A cross-sectional design was used and the relationship between morphometric VF and T2DM in adult women was evaluated. The cases were adult women with morphometric VF and the controls were adult women without VF. Thoracic and spinal radiographs in lateral and antero-posterior projections were obtained. Bone mineral density (BMD) values of the lumbar spine (L-BMD) were measured by DXA. Results. A greater number of women with T2DM were found in the VF group (61% vs 31.5%). Non-T2DM women with VF were significantly older and with lower L-BMD than non-T2DM without VF. We observed a negative correlation between age and L-BMD (r=-0.463) in non-T2DM women, but not in the T2DM with FV group. T2DM was a risk factor for prevalent VF with OR of 3.540 (IC95% 1.750-7.160). Conclusion. Our study showed a higher prevalence of T2DM in the VF group. T2DM women with VF were younger and had higher L-BMD than non-T2DM women, L-BMD did not correlate with age and VF were not distributed according to BMD-L and age. (AU)


Introducción. La diabetes es una enfermedad crónica asociada con comorbilidades importantes. La diabetes tipo 2 (DM2) se asocia con un riesgo tres veces mayor de fractura de cadera pero la asociación con fracturas vertebrales (FV) es contradictoria. Nuestro objetivo fue evaluar los factores involucrados en las FV prevalentes en mujeres adultas con y sin DM2. Materiales y métodos. Se realizó un diseño transversal y se evaluó la relación entre FV morfométrica y DM2 en mujeres adultas. Los casos fueron mujeres adultas con FV morfométricas y los controles fueron mujeres adultas sin FV. Se obtuvieron radiografías torácicas y espinales en proyecciones lateral y anteroposterior. Los valores de densidad mineral ósea (DMO) de la columna lumbar (DMO-L) se midieron por DXA. Resultados. Se observó un mayor número de mujeres con DM2 en el grupo de FV (61% frente a 31.5%). Las mujeres sin DM2 con FV eran significativamente mayores y con una DMO-L más baja que las mujeres sin DM2 sin FV. Observamos una correlación negativa entre la edad y la DMO-L (r= -0.463) en mujeres sin DM2 y FV, pero no en DM2 con FV. La DM2 fue un factor de riesgo para FV prevalente con un OR 3.540 (IC95% 1.750-7.160). Conclusión. Nuestro estudio demostró una mayor prevalencia de DM2 en el grupo de FV. Las mujeres con DM2 y FV eran más jóvenes y tenían mayor DMO-L que las mujeres sin DM2, la DMO-L no correlacionó con la edad y las FV no se distribuyeron de acuerdo a la DMO-L y edad. (AU)


Asunto(s)
Humanos , Femenino , Adulto , Adulto Joven , Fracturas de la Columna Vertebral/microbiología , Diabetes Mellitus Tipo 2/complicaciones , Osteoporosis/complicaciones , Vitamina D/sangre , Absorciometría de Fotón , Densidad Ósea , Estudios Transversales , Factores de Riesgo , Fracturas de la Columna Vertebral/inducido químicamente , Fracturas de la Columna Vertebral/diagnóstico por imagen , Factores de Edad , Tiazolidinedionas/uso terapéutico , PPAR gamma/uso terapéutico , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Rosiglitazona/uso terapéutico , Inhibidores del Cotransportador de Sodio-Glucosa 2/efectos adversos , Pioglitazona/uso terapéutico , Hipoglucemiantes/efectos adversos , Hipoglucemiantes/uso terapéutico
20.
J Pharmacol Exp Ther ; 375(1): 76-91, 2020 10.
Artículo en Inglés | MEDLINE | ID: mdl-32764153

RESUMEN

Sodium glucose cotransporter 2 inhibitors (SGLT2i) reduce cardiovascular events and onset and progression of renal disease by mechanisms that remain incompletely understood but may include clearance of interstitial congestion and reduced glomerular hydrostatic pressure. The ongoing DAPASALT mechanistic clinical study will evaluate natriuretic, diuretic, plasma/extracellular volume, and blood pressure responses to dapagliflozin in people with type 2 diabetes with normal or impaired renal function (D-PRF and D-IRF, respectively) and in normoglycemic individuals with renal impairment (N-IRF). In this study, a mathematical model of renal physiology, pathophysiology, and pharmacology was used to prospectively predict changes in sodium excretion, blood and interstitial fluid volume (IFV), blood pressure, glomerular filtration rate, and albuminuria in DAPASALT. After validating the model with previous diabetic nephropathy trials, virtual patients were matched to DAPASALT inclusion/exclusion criteria, and the DAPASALT protocol was simulated. Predicted changes in glycosuria, blood pressure, glomerular filtration rate, and albuminuria were consistent with other recent studies in similar populations. Predicted albuminuria reductions were 46% in D-PRF, 34.8% in D-IRF, and 14.2% in N-IRF. The model predicts a similarly large IFV reduction between D-PRF and D-IRF and less, but still substantial, IFV reduction in N-IRF, even though glycosuria is attenuated in groups with impaired renal function. When DAPASALT results become available, comparison with these simulations will provide a basis for evaluating how well we understand the cardiorenal mechanism(s) of SGLT2i. Meanwhile, these simulations link dapagliflozin's renal mechanisms to changes in IFV and renal biomarkers, suggesting that these benefits may extend to those with impaired renal function and individuals without diabetes. SIGNIFICANCE STATEMENT: Mechanisms of SGLT2 inhibitors' cardiorenal benefits remain incompletely understood. We used a mathematical model of renal physiology/pharmacology to prospectively predict responses to dapagliflozin in the ongoing DAPASALT study. Key predictions include similarly large interstitial fluid volume (IFV) reductions between subjects with normal and impaired renal function and less, but still substantial, IFV reduction in those without diabetes, even though glycosuria is attenuated in these groups. Comparing prospective simulations and study results will assess how well we understand the cardiorenal mechanism(s) of SGLT2 inhibitors.


Asunto(s)
Compuestos de Bencidrilo/uso terapéutico , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Nefropatías Diabéticas/fisiopatología , Tasa de Filtración Glomerular/efectos de los fármacos , Glucósidos/uso terapéutico , Riñón/efectos de los fármacos , Modelos Biológicos , Insuficiencia Renal/fisiopatología , Inhibidores del Cotransportador de Sodio-Glucosa 2/uso terapéutico , Compuestos de Bencidrilo/efectos adversos , Ensayos Clínicos Fase IV como Asunto , Diabetes Mellitus Tipo 2/metabolismo , Nefropatías Diabéticas/metabolismo , Tasa de Filtración Glomerular/fisiología , Glucósidos/efectos adversos , Humanos , Riñón/metabolismo , Riñón/fisiopatología , Ensayos Clínicos Controlados Aleatorios como Asunto , Insuficiencia Renal/metabolismo , Índice de Severidad de la Enfermedad , Transportador 2 de Sodio-Glucosa/metabolismo , Inhibidores del Cotransportador de Sodio-Glucosa 2/efectos adversos
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