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2.
Curr Opin Cardiol ; 35(2): 178-186, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31804229

RESUMO

PURPOSE OF REVIEW: The aim of this article is to provide practical recommendations on safe initiation of sodium-glucose cotransporter 2 (SGLT2) inhibitors to in-patients as well as management of those who are already on SGLT2 inhibitors. RECENT FINDINGS: Robust data from stable outpatient cohorts indicate that the SGLT2 inhibitors are associated with clinically meaningful reductions in major adverse cardiovascular events, lower rates of hospitalization for heart failure, and a reduction in major kidney outcomes There is however a lack of information on how to initiate and manage SGLT2 inhibitors in an acute in-patient setting. SUMMARY: SGLT2 inhibitors may be cautiously appropriate for in-patients if all the criteria for safe use are met but good clinical judgment must prevail. Temporary withholding of SGLT2 inhibitors is appropriate in hospitalized patients during a period of stress and/or insulinopenia.

3.
Vasc Med ; : 1358863X19880268, 2019 Nov 10.
Artigo em Inglês | MEDLINE | ID: mdl-31709912

RESUMO

The left ventricular outflow tract (LVOT) velocity time integral (VTI) is an easily measured echocardiographic stroke volume index analog. Low values predict adverse outcomes in left ventricular failure. We postulate the left ventricular VTI may be a signal of right ventricular dysfunction in acute pulmonary embolism, and therefore a predictor of poor outcomes. We retrospectively reviewed echocardiograms on all Pulmonary Embolism Response Team activations at our institution at the time of pulmonary embolism diagnosis. Low LVOT VTI was defined as ⩽ 15 cm. We examined two composite outcomes: (1) in-hospital death or cardiac arrest; and (2) shock or need for primary reperfusion therapies. Sixty-one of 188 patients (32%) had a LVOT VTI of ⩽ 15 cm. Low VTI was associated with in-hospital death or cardiac arrest (odds ratio (OR) 6, 95% CI 2, 17.9; p = 0.0014) and shock or need for reperfusion (OR 23.3, 95% CI 6.6, 82.1; p < 0.0001). In a multivariable model, LVOT VTI ⩽ 15 remained significant for death or cardiac arrest (OR 3.48, 95% CI 1.02, 11.9; p = 0.047) and for shock or need for reperfusion (OR 8.12, 95% CI 1.62, 40.66; p = 0.011). Among intermediate-high-risk patients, low VTI was the only variable associated with the composite outcome of death, cardiac arrest, shock, or need for reperfusion (OR 14, 95% CI 1.7, 118.4; p = 0.015). LVOT VTI is associated with adverse short-term outcomes in acute pulmonary embolism. The VTI may help risk stratify patients with intermediate-high-risk pulmonary embolism.

4.
Circulation ; 140(21): 1693-1702, 2019 Nov 19.
Artigo em Inglês | MEDLINE | ID: mdl-31434508

RESUMO

BACKGROUND: SGLT2 (sodium-glucose cotransporter 2) inhibitors lower cardiovascular events in type 2 diabetes mellitus but whether they promote direct cardiac effects remains unknown. We sought to determine if empagliflozin causes a decrease in left ventricular (LV) mass in people with type 2 diabetes mellitus and coronary artery disease. METHODS: Between November 2016 and April 2018, we recruited 97 individuals ≥40 and ≤80 years old with glycated hemoglobin 6.5% to 10.0%, known coronary artery disease, and estimated glomerular filtration rate ≥60mL/min/1.73m2. The participants were randomized to empagliflozin (10 mg/day, n=49) or placebo (n=48) for 6 months, in addition to standard of care. The primary outcome was the 6-month change in LV mass indexed to body surface area from baseline as measured by cardiac magnetic resonance imaging. Other measures included 6-month changes in LV end-diastolic and -systolic volumes indexed to body surface area, ejection fraction, 24-hour ambulatory blood pressure, hematocrit, and NT-proBNP (N-terminal pro b-type natriuretic peptide). RESULTS: Among the 97 participants (90 men [93%], mean [standard deviation] age 62.8 [9.0] years, type 2 diabetes mellitus duration 11.0 [8.2] years, estimated glomerular filtration rate 88.4 [16.9] mL/min/1.73m2, LV mass indexed to body surface area 60.7 [11.9] g/m2), 90 had evaluable imaging at follow-up. Mean LV mass indexed to body surface area regression over 6 months was 2.6 g/m2 and 0.01 g/m2 for those assigned empagliflozin and placebo, respectively (adjusted difference -3.35 g/m2; 95% CI, -5.9 to -0.81g/m2, P=0.01). In the empagliflozin-allocated group, there was significant lowering of overall ambulatory systolic blood pressure (adjusted difference -6.8mmHg, 95% CI -11.2 to -2.3mmHg, P=0.003), diastolic blood pressure (adjusted difference -3.2mmHg; 95% CI, -5.8 to -0.6mmHg, P=0.02) and elevation of hematocrit (P=0.0003). CONCLUSIONS: Among people with type 2 diabetes mellitus and coronary artery disease, SGLT2 inhibition with empagliflozin was associated with significant reduction in LV mass indexed to body surface area after 6 months, which may account in part for the beneficial cardiovascular outcomes observed in the EMPA-REG OUTCOME (BI 10773 [Empagliflozin] Cardiovascular Outcome Event Trial in Type 2 Diabetes Mellitus Patients) trial. CLINICAL TRIAL REGISTRATION: URL: https://www.clinicaltrials.gov. Unique identifier: NCT02998970.

5.
Diabetes Obes Metab ; 21(10): 2192-2202, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31183975

RESUMO

Recent phase 3 clinical trials have evaluated the impact of adding sodium-glucose co-transporter (SGLT) inhibitors to the type 1 diabetes armamentarium. These trials studied SGLT2 inhibitors (dapagliflozin and empagliflozin) and a dual SGLT1 and SGLT2 inhibitor (sotagliflozin), and demonstrated that these oral non-insulin antihyperglycaemic medications are able not only to improve glycaemic control, but also to reduce body weight and extend time in range without increasing rates of hypoglycaemia in type 1 diabetes. Diabetic ketoacidosis (DKA) is a feature of type 1 diabetes and the risk is increased when SGLT inhibitors are used in type 1 diabetes. To minimize the risk of DKA and still gain the multiple benefits, we developed the "STOP DKA Protocol ", an easily accessible and practical tool, that provides a risk mitigation strategy for reducing DKA in patients with type 1 diabetes being treated with SGLT inhibitors.

6.
Can J Diabetes ; 43(2): 136-145, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30195966

RESUMO

Guidelines increasingly highlight the importance of multifactorial management in type 2 diabetes, in contrast to the more traditional focus on glycemic control. Semaglutide, a recently approved glucagon-like peptide-1 receptor agonist, is indicated in Canada for adults with type 2 diabetes to improve glycemic control as monotherapy with diet and exercise when metformin is inappropriate or as an add-on to either metformin alone or metformin plus a sulfonylurea or basal insulin. The Semaglutide Unabated Sustainability in Treatment of Type 2 Diabetes (SUSTAIN) clinical trial program for semaglutide comprises 6 pivotal global phase 3a trials (SUSTAIN 1 through 6) and 2 Japanese phase 3a trials. Phase 3b trials include SUSTAIN 7, and SUSTAIN 8 and 9 (both ongoing). Results from the completed trials support the superiority of semaglutide for reduction of glycated hemoglobin levels and weight loss vs. placebo as well as active comparators, including sitagliptin, exenatide extended-release, dulaglutide and insulin glargine. SUSTAIN 6 trial data confirmed cardiovascular safety and demonstrated significant reductions in major cardiovascular events with semaglutide vs. placebo, an outcome that confirmed the noninferiority of semaglutide. The robust and sustained effects of semaglutide on glycated hemoglobin levels and weight loss vs. comparators, as well as its safety and possible cardiovascular benefit, address an unmet need in the treatment of type 2 diabetes. This article overviews data from across the semaglutide clinical trial program, including efficacy and safety results and findings from post hoc analyses. The potential place of semaglutide in clinical practice is discussed.


Assuntos
Diabetes Mellitus Tipo 2/tratamento farmacológico , Peptídeos Semelhantes ao Glucagon/uso terapêutico , Glicemia/efeitos dos fármacos , Peso Corporal/efeitos dos fármacos , Canadá , Ensaios Clínicos como Assunto , Peptídeos Semelhantes ao Glucagon/efeitos adversos , Hemoglobina A Glicada/efeitos dos fármacos , Hemoglobina A Glicada/metabolismo , Humanos , Resultado do Tratamento
7.
Can J Diabetes ; 43(6): 384-391, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-30554985

RESUMO

OBJECTIVES: To describe the clinical histories and management of adults with type 2 diabetes who were not reaching their target glycated hemoglobin (A1C) levels and to identify barriers to achieving therapeutic goals. METHODS: Practice assessment surveys and practice audits were completed by 88 primary care physicians (PCPs) in the Diabetes Mellitus Assessment of Clinical managemenT In ONtario (DM-ACTION) program and by 56 diabetes specialists in the Diabetes Mellitus IMproving PAtient Care in our communiTies (DM-IMPACT) program. The DM-ACTION audit analyzed data from 1,173 adults with A1C levels ≥7.3% who were not prescribed insulin; the DM-IMPACT audit included 135 individuals with similar characteristics. RESULTS: Most PCPs (92%) and specialists (88%) stated that they typically recommend A1C levels of ≤7.0%; more than 90% indicated that they adjusted antihyperglycemic therapy within 3 months if suboptimal A1C targets endured. Among the DM-ACTION patients, the median A1C level was 7.8%; the median time between the last 2 A1C tests was 5 months; 58% were taking ≤2 noninsulin antihyperglycemic agents; and adjustment of glucose-lowering therapy was noted for only 56%. The corresponding values for the DM-IMPACT patients were 8.0%, 4 months, 43% and 68%, respectively. PCPs and specialists attributed patients' factors and patients' adherence as primary causes of poor achievement of guideline-recommended targets. PCPs perceived patients' factors as the predominant barrier to optimizing care, but the specialists believed that therapeutic inertia stems from a wide range and a varied combination of patient-centric factors. CONCLUSIONS: Type 2 diabetes remains a health-care challenge in Canada and globally. Primary care physicians and specialists attributed patients' factors as principal obstacles to optimal diabetes management. However, physician-associated therapeutic inertia may also be an important barrier to unmet therapeutic goals.


Assuntos
Diabetes Mellitus Tipo 2/prevenção & controle , Hemoglobina A Glicada/análise , Hipoglicemiantes/uso terapêutico , Adesão à Medicação/estatística & dados numéricos , Determinação de Necessidades de Cuidados de Saúde , Assistência ao Paciente/normas , Médicos de Atenção Primária/normas , Adulto , Biomarcadores/análise , Glicemia/análise , Diabetes Mellitus Tipo 2/metabolismo , Gerenciamento Clínico , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Assistência ao Paciente/métodos , Guias de Prática Clínica como Assunto/normas , Prognóstico , Especialização/estatística & dados numéricos , Inquéritos e Questionários
8.
Respir Med ; 141: 37-46, 2018 08.
Artigo em Inglês | MEDLINE | ID: mdl-30053970

RESUMO

BACKGROUND: Familial dysautonomia (Riley-Day syndrome, hereditary sensory autonomic neuropathy type-III) is a rare genetic disease caused by impaired development of sensory and afferent autonomic nerves. As a consequence, patients develop neurogenic dysphagia with frequent aspiration, chronic lung disease, and chemoreflex failure leading to severe sleep disordered breathing. The purpose of these guidelines is to provide recommendations for the diagnosis and treatment of respiratory disorders in familial dysautonomia. METHODS: We performed a systematic review to summarize the evidence related to our questions. When evidence was not sufficient, we used data from the New York University Familial Dysautonomia Patient Registry, a database containing ongoing prospective comprehensive clinical data from 670 cases. The evidence was summarized and discussed by a multidisciplinary panel of experts. Evidence-based and expert recommendations were then formulated, written, and graded using the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) system. RESULTS: Recommendations were formulated for or against specific diagnostic tests and clinical interventions. Diagnostic tests reviewed included radiological evaluation, dysphagia evaluation, gastroesophageal evaluation, bronchoscopy and bronchoalveolar lavage, pulmonary function tests, laryngoscopy and polysomnography. Clinical interventions and therapies reviewed included prevention and management of aspiration, airway mucus clearance and chest physical therapy, viral respiratory infections, precautions during high altitude or air-flight travel, non-invasive ventilation during sleep, antibiotic therapy, steroid therapy, oxygen therapy, gastrostomy tube placement, Nissen fundoplication surgery, scoliosis surgery, tracheostomy and lung lobectomy. CONCLUSIONS: Expert recommendations for the diagnosis and management of respiratory disease in patients with familial dysautonomia are provided. Frequent reassessment and updating will be needed.


Assuntos
Consenso , Disautonomia Familiar/epidemiologia , Transtornos Respiratórios/epidemiologia , Transtornos Respiratórios/terapia , Lavagem Broncoalveolar/métodos , Broncoscopia/métodos , Síndrome de Brugada/epidemiologia , Transtornos de Deglutição/diagnóstico por imagem , Transtornos de Deglutição/fisiopatologia , Disautonomia Familiar/complicações , Disautonomia Familiar/mortalidade , Disautonomia Familiar/fisiopatologia , Prática Clínica Baseada em Evidências/métodos , Humanos , New York/epidemiologia , Pneumonia Aspirativa/diagnóstico por imagem , Pneumonia Aspirativa/fisiopatologia , Polissonografia/métodos , Estudos Prospectivos , Transtornos Respiratórios/diagnóstico por imagem , Transtornos Respiratórios/patologia , Testes de Função Respiratória/métodos
9.
Diabetes Obes Metab ; 20(9): 2064-2074, 2018 09.
Artigo em Inglês | MEDLINE | ID: mdl-29707875

RESUMO

Despite the availability of long-term data demonstrating the benefits of timely and aggressive intensification of antihyperglycaemic regimens among individuals with type 2 diabetes, intensification beyond basal insulin continues to be suboptimal and a global challenge. This review summarizes the evidence surrounding the various options of advancing glucose-lowering management beyond basal insulin and provides a practical algorithm to assist in optimizing patient care and enhancing glycaemic target achievements.


Assuntos
Algoritmos , Diabetes Mellitus Tipo 2/tratamento farmacológico , Hipoglicemiantes/administração & dosagem , Insulina de Ação Prolongada/administração & dosagem , Glicemia/efeitos dos fármacos , Diabetes Mellitus Tipo 2/sangue , Esquema de Medicação , Hemoglobina A Glicada/efeitos dos fármacos , Humanos
10.
Curr Med Res Opin ; 34(1): 1-10, 2018 01.
Artigo em Inglês | MEDLINE | ID: mdl-28836861

RESUMO

BACKGROUND: Diabetes mellitus is a serious and increasingly prevalent condition in Canada and around the world. Treatment strategies have become increasingly complex, with a widening array of pharmacological agents available for glycemic management in type 2 diabetes mellitus (T2DM). New therapies that act in concert with available basal insulins may represent alternatives to basal insulin intensification with prandial or pre-mixed insulin. Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) have recently shown promise as useful additions to basal insulin, with significant reductions in glycated hemoglobin and potentially beneficial effects on body weight. This review will focus on pivotal clinical trials to assess the potential benefits of adding prandial GLP-1 RAs to basal insulin in patients with T2DM. METHODS: Clinical studies combining prandial GLP-1 RAs and basal insulin (published between 2011 and July 2017) were identified and reviewed in PubMed, the Cochrane Central Register of Clinical Trials (Issue 6, June 2017), and clinicaltrials.gov. RESULTS: Most of the studies presented in this review show that the addition of a prandial GLP-1 RA to basal insulin results in equal or slightly superior efficacy compared to the addition of prandial insulin, together with weight loss and less hypoglycemia. CONCLUSIONS: The results of the studies suggest that a prandial GLP-1 RA as an add-on to basal insulin may be a safe and effective treatment intensification option (vs basal-plus or basal-bolus insulin).


Assuntos
Diabetes Mellitus Tipo 2/tratamento farmacológico , Receptor do Peptídeo Semelhante ao Glucagon 1/agonistas , Hipoglicemiantes/uso terapêutico , Insulina/uso terapêutico , Glicemia/análise , Quimioterapia Combinada , Humanos , Insulina/administração & dosagem
11.
Can J Diabetes ; 42(3): 325-334, 2018 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-28822777

RESUMO

Diabetic kidney disease (DKD) is a group of chronic kidney diseases that is associated with significant cardiovascular as well as all-cause morbidity and mortality. Although DKD is often progressive in nature, its evolution can be modified by intensive management of glycemia and blood pressure and inhibition of the renin-angiotensin-aldosterone system. This review provides an overview of how multifactorial interventions can provide renal protection and includes a discussion of the nonglycemic effects of incretin-based diabetes therapies (glucagon-like peptide-1 receptor agonists and dipeptidyl peptidase 4 inhibitors) and sodium-glucose cotransporter-2 inhibitors within the kidney in patients with type 2 diabetes.


Assuntos
Diabetes Mellitus Tipo 2/tratamento farmacológico , Nefropatias Diabéticas/tratamento farmacológico , Glicemia , Pressão Sanguínea , Inibidores da Dipeptidil Peptidase IV/uso terapêutico , Feminino , Humanos , Hipoglicemiantes/uso terapêutico , Pessoa de Meia-Idade , Inibidores do Transportador 2 de Sódio-Glicose
12.
Clin Ther ; 39(12): 2438-2447, 2017 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-29174215

RESUMO

PURPOSE: Type 2 diabetes remains a poorly managed disease, with only about half of individuals with type 2 diabetes meeting guideline-recommended glycosylated hemoglobin (HbA1C) targets. A major proportion of those who have not met HbA1C goals have an HbA1C <8.0% to 8.5%. In practice, it is quite common to have to decide between dipeptidyl peptidase-4 inhibitors (DPP-4i) and sodium-glucose cotransporter-2 inhibitors (SGLT2i) as add-ons to metformin to help these individuals meet their HbA1C goals. This commentary reviews and provides guidance on how baseline factors can assist in the decision between the 2 classes or using both as add-ons to metformin. METHODS: The important clinical studies comparing the glycemic efficacy of DPP-4i versus SGLT2i or their combination as add-ons to metformin with a focus on the influence of baseline HbA1C on glycemic efficacy will be discussed and interpreted. The impact of estimated glomerular filtration rate and age on the glycemic efficacy of DPP-4i and SGLT2i will also be put into perspective. FINDINGS: At HbA1C <8.0% to 8.5%, HbA1C lowering is slightly greater with DPP-4i than with SGLT2i as an add-on to metformin; SGLT2i are associated with larger HbA1C improvements than DPP-4i at higher HbA1C levels. In cases of HbA1C ≥8.0%, dual DPP-4i-SGLT2i add-on therapy to metformin should be considered to help more patients achieve glycemic targets. The glycemic efficacy of SGLT2i, but not DPP-4i, declines with progressive renal insufficiency. In older adults, DPP-4i maintain their tolerability and efficacy, while SGLT2i may become less efficacious due to reduced renal function, and may be associated with higher rates of volume-related adverse effects. IMPLICATIONS: Although both DPP-4i and SGLT2i are effective add-on antihyperglycemic therapies to metformin monotherapy, baseline characteristics, such as HbA1C, renal function, and age, should be considered when choosing between the 2 classes to allow for optimal and timely diabetes management.


Assuntos
Diabetes Mellitus Tipo 2/tratamento farmacológico , Inibidores da Dipeptidil Peptidase IV/uso terapêutico , Metformina/uso terapêutico , Inibidores do Transportador 2 de Sódio-Glicose , Glicemia/análise , Diabetes Mellitus Tipo 2/sangue , Quimioterapia Combinada , Hemoglobina A Glicada/análise , Humanos , Transportador 2 de Glucose-Sódio
13.
Can J Diabetes ; 41(5): 517-523, 2017 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-28942789

RESUMO

Sodium-glucose cotransporter 2 (SGTL2) inhibitors are a novel class of antihyperglycemic agents that work in an insulin-independent manner by promoting urinary glucose excretion. In addition to efficacious glucose lowering, they exert beneficial effects on blood pressure and weight while avoiding hypoglycemia unless combined with insulin or insulin secretagogues. This review explores the mechanism of action of SGLT2 inhibitors, their effects on glycated hemoglobin, weight, blood pressure and hypoglycemia, potential adverse effects, renal considerations and cardiovascular outcomes.


Assuntos
Diabetes Mellitus Tipo 2/tratamento farmacológico , Hipoglicemiantes/uso terapêutico , Inibidores do Transportador 2 de Sódio-Glicose , Gerenciamento Clínico , Humanos , Transportador 2 de Glucose-Sódio
14.
CMAJ Open ; 5(1): E152-E177, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28459046

RESUMO

BACKGROUND: Given recent discrepant results from randomized controlled trials (RCTs), we examined the totality of RCT evidence assessing the association between dipeptidyl peptidase-4 (DPP-4) inhibitors and heart failure. METHODS: MEDLINE, Embase and ClinicalTrials.gov were searched without language restrictions to August 2016 for RCTs comparing DPP-4 inhibitors to placebo or no therapy for a period of 24 weeks or more. We included all heart failure outcomes when listed either as a serious adverse event or adverse event. Pooled analyses used random-effects. RESULTS: We identified 100 RCTs (n = 79 867) - 3 large cardiovascular-safety RCTs (SAVOR-TIMI 53[saxagliptin]/n = 16 492, EXAMINE[alogliptin]/n = 5380, and TECOS[sitagliptin]/n = 14 735), and 97 smaller RCTs with a primary outcome that was usually change in glycated hemoglobin. Virtually all RCTs were high-quality, multicentre, placebo-controlled trials. A total of 96% (1192/1244) of heart failure events were prespecified, blindly adjudicated and required hospital admission. Pooled results suggested a 13% increase in heart failure (relative risk [RR] 1.13, 95% confidence interval [CI] 1.01-1.26, I2 = 0%; 32 RCTs, n = 54 640, 1244 events). When including only the 3 large RCTs, the increase was similar, but not significant (RR 1.14, 95% CI 0.97-1.32; 3 RCTs, n = 36 543, 1169 adjudicated events; number needed to harm 246) owing to heterogeneity (I2 = 42%), which lead to wider CIs, because SAVOR-TIMI 53 showed increased heart failure (RR 1.26, 95% CI 1.06-1.49) and TECOS showed no effect (RR 1.00, 95% CI 0.83-1.19). INTERPRETATION: Despite pooled data from 79 867 patients, whether DPP-4 inhibitors increase heart failure overall or exhibit within-class differences remains unresolved. Our results highlight the importance of ongoing trials that are comparing DPP-4 inhibitors to placebo, although no large cardiovascular-safety RCTs are comparing different DPP-4 inhibitors to each other; consequently, these will address the overall but not class-difference question.

15.
Can J Diabetes ; 2017 Mar 03.
Artigo em Inglês | MEDLINE | ID: mdl-28262472

RESUMO

The Publisher regrets that this article is an accidental duplication of an article that has already been published, http://dx.doi.org/10.1016/j.jcjd.2016.11.008. The duplicate article has therefore been withdrawn. The full Elsevier Policy on Article Withdrawal can be found at https://www.elsevier.com/about/our-business/policies/article-withdrawal.

17.
Diabetes Obes Metab ; 19(2): 275-283, 2017 02.
Artigo em Inglês | MEDLINE | ID: mdl-27767249

RESUMO

AIMS: To explore the treatment outcomes in adult patients with type 2 diabetes (T2D) enrolled in the GetGoal trials of lixisenatide (LIXI), and the predictive effects of baseline characteristics on outcomes. METHODS: This study was a pooled analysis of patient-level data from the LIXI GetGoal studies comparing LIXI and placebo. Patients were divided into baseline therapy groups: those receiving oral antidiabetes drugs (OADs) at baseline (n = 2760) or those receiving basal insulin at baseline (n = 1198). RESULTS: Compared with placebo, LIXI treatment led to significantly greater reductions in glycated haemoglobin (HbA1c), and greater achievement of the composite endpoint of HbA1c <7.0% (53 mmol/mol) with no symptomatic hypoglycaemia and no weight gain in either the OAD (34% vs 18%; P < .0001) or the basal insulin groups (19% vs 10%; P < .0001). Treatment with LIXI was associated with a greater percentage of patients experiencing a symptomatic hypoglycaemic event compared with placebo in both the OAD (5% vs 3%; P = .0098) and basal insulin groups (27% vs 17%; P < .0001). In assessing baseline factors that were predictors of treatment outcomes, only baseline HbA1c and LIXI treatment were strong predictors of outcomes in both the OAD and basal insulin groups. No other baseline characteristic had such a large or consistent clinically relevant predictive effect across treatment outcomes. CONCLUSIONS: The results from this study show that irrespective of baseline characteristics, LIXI treatment, as an add-on to OAD or basal insulin therapy, is effective in reducing HbA1c and achieving composite endpoints.


Assuntos
Diabetes Mellitus Tipo 2/tratamento farmacológico , Hipoglicemiantes/uso terapêutico , Insulina/uso terapêutico , Peptídeos/uso terapêutico , Adulto , Idoso , Glicemia/metabolismo , Ensaios Clínicos Fase III como Assunto , Diabetes Mellitus Tipo 2/metabolismo , Quimioterapia Combinada , Feminino , Hemoglobina A Glicada/metabolismo , Humanos , Hipoglicemia/induzido quimicamente , Masculino , Pessoa de Meia-Idade , Resultado do Tratamento , Ganho de Peso
18.
Clin Ther ; 38(12): 2654-2664.e1, 2016 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-28003053

RESUMO

PURPOSE: Sodium-glucose cotransporter 2 (SGLT2) inhibitors are the newest class of antihyperglycemic agents available on the market. Regulator warnings and concerns regarding the risk of developing diabetic ketoacidosis (DKA), however, have dampened enthusiasm for the class despite the combined glycemic, blood pressure, and occasional weight benefits of SGLT2 inhibitors. With the goal of improving patient safety, a cross-Canada expert panel and writing group were convened to review the evidence to-date on reported SGLT2 inhibitor-related DKA incidents and to offer recommendations for preventing and recognizing patients with SGLT2 inhibitor-associated DKA. METHODS: Reports covering DKA events in subjects taking SGLT2 inhibitors that were published in PubMed, presented at professional conferences, or in the public domain from January 2013 to mid-August 2016 were reviewed by the group independently and collectively. Practical recommendations for diagnosis and prevention were established by the panel. FINDINGS: DKA is rarely associated with SGLT2 inhibitor therapy. Patients with SGLT2 inhibitor-associated DKA may be euglycemic (plasma glucose level <14 mmol/L). DKA is more likely in patients with insulin-deficient diabetes, including those with type 2 diabetes, and is typically precipitated by insulin omission or dose reduction, severe acute illness, dehydration, extensive exercise, surgery, low-carbohydrate diets, or excessive alcohol intake. SGLT2 inhibitor-associated DKA may be prevented by withholding SGLT2 inhibitors when precipitants develop, avoiding insulin omission or inappropriate insulin dose reduction, and by following sick day protocols as recommended. IMPLICATIONS: Preventive strategies should help avoid SGLT2 inhibitor-associated DKA. All SGLT2 inhibitor-treated patients presenting with signs or symptoms of DKA should be suspected to have DKA and be investigated for DKA, especially euglycemic patients. If DKA is diagnosed, SGLT2 inhibitor treatment should be stopped, and the DKA should be treated with a traditional treatment protocol.


Assuntos
Cetoacidose Diabética/induzido quimicamente , Hipoglicemiantes/efeitos adversos , Inibidores do Transportador 2 de Sódio-Glicose , Glicemia/análise , Canadá/epidemiologia , Diabetes Mellitus Tipo 2/tratamento farmacológico , Cetoacidose Diabética/diagnóstico , Cetoacidose Diabética/epidemiologia , Cetoacidose Diabética/prevenção & controle , Humanos , Incidência , Insulina/administração & dosagem , Transportador 2 de Glucose-Sódio
19.
Can J Diabetes ; 35(5): 518-27, 2011 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-24854977

RESUMO

The leading cause of morbidity and mortality in type 2 diabetes mellitus is cardiovascular disease. There is a need for type 2 diabetes therapies that act in concert with available agents to provide adequate glycemic control without causing hypoglycemia and weight gain, which are associated with increases in cardiovascular risk. Incretin-based agents-dipeptidyl peptidase-4 inhibitors and glucagon-like peptide-1 receptor agonists-are the newest class of antihyperglycemic therapies. Liraglutide and exenatide, glucagon-like peptide-1 receptor agonists recently approved in Canada, have been shown to effectively lower blood glucose levels while also having beneficial effects on body weight and systolic blood pressure. The objective of this article is to review and discuss incretin-based agents, with a focus on their effects on blood glucose control, body weight and cardiovascular risk factors in patients with type 2 diabetes. Relevant data were obtained by literature search using the EMBASE, MEDLINE and PubMed databases.

20.
Acta Cardiol ; 60(4): 443-4, 2005 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-16128379

RESUMO

This is a report of a 41-year-old professional male bodybuilder with a history of active anabolic-androgenic steroid abuse and a normal echocardiogram two years prior to admission who experienced a near-fatal arrhythmia during anaesthetic induction for elective orthopaedic surgery. The patient had severe concentric left ventricular hypertrophy, diffuse left ventricular hypokinesis, decreased ejection fraction and inducible monomorphic ventricular tachycardia. A single-chamber cardioverter/defibrillator was inserted.


Assuntos
Anestesia/efeitos adversos , Arritmias Cardíacas/etiologia , Exercício/fisiologia , Parada Cardíaca/etiologia , Adulto , Anabolizantes/administração & dosagem , Androgênios/administração & dosagem , Arritmias Cardíacas/terapia , Desfibriladores Implantáveis , Parada Cardíaca/fisiopatologia , Parada Cardíaca/terapia , Humanos , Hipertrofia Ventricular Esquerda , Masculino , Transtornos Relacionados ao Uso de Substâncias/complicações , Resultado do Tratamento , Disfunção Ventricular Esquerda
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