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1.
Isr Med Assoc J ; 23(9): 563-568, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34472231

RESUMO

BACKGROUND: Infants born very prematurely have functionally and structurally immature gastrointestinal tracts. OBJECTIVES: To assess the safety and tolerability of administration of enteral recombinant human (rh) insulin on formula fed preterm infants and to assess whether enteral administration of rh-insulin enhances gastrointestinal tract maturation by reducing the time to reach full enteral feeding. METHODS: A phase 2, multicenter, double-blind, placebo-controlled, randomized study was conducted. Premature infants (26-33 weeks gestation) were randomized 1:1 to receive insulin 400 µU/ml mixed with enteral feeding or placebo added to their formula. The primary efficacy outcome measure was the number of days required to achieve full enteral feeding. Safety outcomes included adverse events and blood glucose levels. RESULTS: The study consisted of 33 infants randomized for the safety population and 31 for efficacy analysis. The mean time to full enteral feeding was 6.37 days (95% confidence interval [95%CI] 4.59-8.15) in the enteral rh-insulin treatment group (n=16) and 8.00 days (95%CI 6.20-9.80) in the placebo group (n=15), which represents a statistically significant reduction of 1.63 days (95%CI 0.29-2.97; P = 0.023). There was no difference in blood glucose levels between the groups and none of the participants experienced hypoglycemia. Adverse events occurred in 9/17 (53%) infants in the enteral rh-insulin group and 12/16 (75%) in the placebo group. CONCLUSIONS: Our trial demonstrated that administration of enteral rh-insulin as supplement to enteral nutrition significantly reduced time to achieve full enteral feeding in preterm infants with a gestational age of 26-33 weeks.


Assuntos
Nutrição Enteral/estatística & dados numéricos , Hipoglicemiantes/administração & dosagem , Recém-Nascido Prematuro , Insulina/administração & dosagem , Glicemia/efeitos dos fármacos , Método Duplo-Cego , Feminino , Idade Gestacional , Humanos , Hipoglicemiantes/efeitos adversos , Recém-Nascido , Insulina/efeitos adversos , Masculino , Fatores de Tempo
2.
Am J Case Rep ; 22: e931960, 2021 Sep 19.
Artigo em Inglês | MEDLINE | ID: mdl-34537806

RESUMO

BACKGROUND The strong association between type 2 diabetes and obesity has been well recognized. Insulin treatment is usually needed at some point in the treatment of patients with type 2 diabetes and obesity to achieve the targeted glycemic control goal. CASE REPORT A 35-year-old woman who had gastric banding for morbid obesity 1 year prior presented to the outpatient clinic with recent onset of shortness of breath and bilateral ankle edema, which were thought to be of cardiac origin. Band slippage occurred a few months after the procedure, and the patient gained weight rapidly thereafter. She had been diagnosed with type 2 diabetes mellitus 8 years earlier, which was treated with oral hypoglycemic medication. Thyroid function tests done 4 months prior to her current presentation revealed normal results. A cardiac assessment showed normal cardiac function with no evidence of heart failure. Repeated thyroid function testing showed new-onset subclinical hypothyroidism. The patient had started insulin therapy 2 weeks before her current presentation, which was probably the main cause of her edema. While continuing insulin, the patient's general condition improved with diuretics therapy, following which she had gastric bypass surgery. CONCLUSIONS Insulin-induced edema is an under-diagnosed problem. It should be considered whenever a patient with uncontrolled diabetes develops rapid body swelling after initiation of insulin therapy. Rigorous research is needed to explore the pathophysiology, prevalence, and treatment of insulin-induced edema.


Assuntos
Diabetes Mellitus Tipo 2 , Obesidade Mórbida , Adulto , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/tratamento farmacológico , Edema/induzido quimicamente , Feminino , Humanos , Hipoglicemiantes/efeitos adversos , Insulina/efeitos adversos , Obesidade Mórbida/complicações
3.
Kidney Int ; 100(3): 513-515, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-34420660

RESUMO

The biguanide metformin has been safely and widely used in the treatment of type 2 diabetes mellitus for decades. Preclinical studies have suggested that it may have a role in slowing disease progression in autosomal dominant polycystic kidney disease. In this issue, Perrone et al. report results from the Trial of Administration of Metformin in PKD (TAME PKD) study, a phase 2 randomized controlled trial investigating the safety and tolerability of metformin in patients in the early stages of autosomal dominant polycystic kidney disease. We discuss the implications of these findings and how they relate to a major phase 3 trial in autosomal dominant polycystic kidney disease that will start later in 2021.


Assuntos
Diabetes Mellitus Tipo 2 , Metformina , Rim Policístico Autossômico Dominante , Diabetes Mellitus Tipo 2/tratamento farmacológico , Humanos , Hipoglicemiantes/efeitos adversos , Metformina/efeitos adversos , Rim Policístico Autossômico Dominante/tratamento farmacológico , Projetos de Pesquisa
8.
Nutrients ; 13(7)2021 Jul 14.
Artigo em Inglês | MEDLINE | ID: mdl-34371917

RESUMO

Diabetes mellitus is a chronic condition characterized by increased blood glucose levels from dysfunctional carbohydrate metabolism. Dietary intervention can help to prevent and manage the disease. Food hydrocolloids have been shown to have favorable properties in relation to glycaemic regulation. However, the use of food hydrocolloids of bacterial origin to modulate glucose responses is much less explored than other types of hydrocolloids. We, therefore, carried out the first review examining the impact of intake of food hydrocolloids of bacterial origin (as a direct supplement or incorporated into foods) on glycemic response in humans. Fourteen studies met the inclusion criteria. They used either xanthan gum, pullulan, or dextran as interventions. There was a wide variation in the amount of hydrocolloid supplementation provided and methods of preparation. Postprandial blood glucose responses were reduced in half of the studies, particularly at higher intake levels and longer chain hydrocolloids. When xanthan gum was added to the cooking process of muffins and rice, a significant reduction in postprandial blood glucose was observed. The use of these hydrocolloids is potentially effective though more research is needed in this area.


Assuntos
Bactérias/química , Glicemia/efeitos dos fármacos , Dextranos/uso terapêutico , Diabetes Mellitus Tipo 2/tratamento farmacológico , Glucanos/uso terapêutico , Controle Glicêmico , Hipoglicemiantes/uso terapêutico , Polissacarídeos Bacterianos/uso terapêutico , Adolescente , Adulto , Idoso , Biomarcadores/sangue , Glicemia/metabolismo , Coloides , Dextranos/efeitos adversos , Dextranos/isolamento & purificação , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/diagnóstico , Feminino , Glucanos/efeitos adversos , Glucanos/isolamento & purificação , Controle Glicêmico/efeitos adversos , Humanos , Hipoglicemiantes/efeitos adversos , Hipoglicemiantes/isolamento & purificação , Masculino , Pessoa de Meia-Idade , Polissacarídeos Bacterianos/efeitos adversos , Polissacarídeos Bacterianos/isolamento & purificação , Resultado do Tratamento , Adulto Jovem
10.
N Engl J Med ; 385(10): 896-907, 2021 09 02.
Artigo em Inglês | MEDLINE | ID: mdl-34215025

RESUMO

BACKGROUND: Four glucagon-like peptide-1 (GLP-1) receptor agonists that are structurally similar to human GLP-1 have been shown to reduce the risk of adverse cardiovascular events among persons with type 2 diabetes. The effect of an exendin-based GLP-1 receptor agonist, efpeglenatide, on cardiovascular and renal outcomes in patients with type 2 diabetes who are also at high risk for adverse cardiovascular events is uncertain. METHODS: In this randomized, placebo-controlled trial conducted at 344 sites across 28 countries, we evaluated efpeglenatide in participants with type 2 diabetes and either a history of cardiovascular disease or current kidney disease (defined as an estimated glomerular filtration rate of 25.0 to 59.9 ml per minute per 1.73 m2 of body-surface area) plus at least one other cardiovascular risk factor. Participants were randomly assigned in a 1:1:1 ratio to receive weekly subcutaneous injections of efpeglenatide at a dose of 4 or 6 mg or placebo. Randomization was stratified according to use of sodium-glucose cotransporter 2 inhibitors. The primary outcome was the first major adverse cardiovascular event (MACE; a composite of nonfatal myocardial infarction, nonfatal stroke, or death from cardiovascular or undetermined causes). RESULTS: A total of 4076 participants were enrolled; 2717 were assigned to receive efpeglenatide and 1359 to receive placebo. During a median follow-up of 1.81 years, an incident MACE occurred in 189 participants (7.0%) assigned to receive efpeglenatide (3.9 events per 100 person-years) and 125 participants (9.2%) assigned to receive placebo (5.3 events per 100 person-years) (hazard ratio, 0.73; 95% confidence interval [CI], 0.58 to 0.92; P<0.001 for noninferiority; P = 0.007 for superiority). A composite renal outcome event (a decrease in kidney function or macroalbuminuria) occurred in 353 participants (13.0%) assigned to receive efpeglenatide and in 250 participants (18.4%) assigned to receive placebo (hazard ratio, 0.68; 95% CI, 0.57 to 0.79; P<0.001). Diarrhea, constipation, nausea, vomiting, or bloating occurred more frequently with efpeglenatide than with placebo. CONCLUSIONS: In this trial involving participants with type 2 diabetes who had either a history of cardiovascular disease or current kidney disease plus at least one other cardiovascular risk factor, the risk of cardiovascular events was lower among those who received weekly subcutaneous injections of efpeglenatide at a dose of 4 or 6 mg than among those who received placebo. (Funded by Sanofi; AMPLITUDE-O ClinicalTrials.gov number, NCT03496298.).


Assuntos
Doenças Cardiovasculares/prevenção & controle , Diabetes Mellitus Tipo 2/tratamento farmacológico , Receptor do Peptídeo Semelhante ao Glucagon 1/agonistas , Hipoglicemiantes/administração & dosagem , Nefropatias/complicações , Prolina/administração & dosagem , Idoso , Doenças Cardiovasculares/complicações , Diabetes Mellitus Tipo 2/complicações , Feminino , Fatores de Risco de Doenças Cardíacas , Humanos , Hipoglicemiantes/efeitos adversos , Injeções Subcutâneas , Nefropatias/prevenção & controle , Masculino , Pessoa de Meia-Idade , Prolina/efeitos adversos
11.
BMJ Case Rep ; 14(7)2021 Jul 08.
Artigo em Inglês | MEDLINE | ID: mdl-34244196

RESUMO

A 58-year-old female with known type 2 diabetes mellitus continued to take her usual medications, including metformin, an ACE inhibitor and a non-steroidal anti-inflammatory drug, while suffering from diarrhoea and vomiting. On presentation to the emergency department, she was found to have a profound lactic acidosis, cardiovascular instability and acute kidney injury. Despite a pH of 6.6, lactate of 14 mmol/L and a brief asystolic cardiac arrest, supportive treatment and the use of renal replacement therapy resulted in rapid improvement in her acid-base abnormalities and haemodynamic parameters. Metformin-associated lactic acidosis is a rare but life-threatening complication of diabetes management. Patient education and awareness amongst clinicians are paramount in the prevention and treatment of this condition.


Assuntos
Acidose Láctica , Injúria Renal Aguda , Diabetes Mellitus Tipo 2 , Metformina , Acidose Láctica/induzido quimicamente , Acidose Láctica/terapia , Injúria Renal Aguda/induzido quimicamente , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/tratamento farmacológico , Feminino , Humanos , Hipoglicemiantes/efeitos adversos , Metformina/efeitos adversos , Pessoa de Meia-Idade
12.
Trials ; 22(1): 464, 2021 Jul 19.
Artigo em Inglês | MEDLINE | ID: mdl-34281590

RESUMO

BACKGROUND: Preclinical studies demonstrated that glucagon-like peptide 1 (GLP-1) is locally synthesized in taste bud cells and that GLP-1 receptor exists on the gustatory nerves in close proximity to GLP-1-containing taste bud cells. This local paracrine GLP-1 signalling seems to be specifically involved in the perception of sweets. However, the role of GLP-1 in taste perception remains largely unaddressed in clinical studies. Whether any weight-reducing effects of GLP-1 receptor agonists are mediated through the modulation of taste perception is currently unknown. METHODS AND ANALYSIS: This is an investigator-initiated, randomized single-blind, placebo-controlled clinical trial. We will enrol 30 women with obesity and polycystic ovary syndrome (PCOS). Participants will be randomized in a 1:1 ratio to either semaglutide 1.0 mg or placebo for 16 weeks. The primary endpoints are alteration of transcriptomic profile of tongue tissue as changes in expression level from baseline to follow-up after 16 weeks of treatment, measured by RNA sequencing, and change in taste sensitivity as detected by chemical gustometry. Secondary endpoints include change in neural response to visual food cues and to sweet-tasting substances as assessed by functional MRI, change in body weight, change in fat mass and change in eating behaviour and food intake. DISCUSSION: This is the first study to investigate the role of semaglutide on taste perception, along with a neural response to visual food cues in reward processing regions. The study may identify the tongue and the taste perception as a novel target for GLP-1 receptor agonists. ETHICS AND DISSEMINATIONS: The study has been approved by the Slovene National Medical Ethics Committee and will be conducted in accordance with the Declaration of Helsinki and Good Clinical Practice guidelines. Results will be submitted for publication in an international peer-reviewed scientific journal. TRIAL REGISTRATION: ClinicalTrials.gov NCT04263415 . Retrospectively registered on 10 February 2020.


Assuntos
Diabetes Mellitus Tipo 2 , Receptor do Peptídeo Semelhante ao Glucagon 1 , Método Duplo-Cego , Feminino , Peptídeos Semelhantes ao Glucagon , Humanos , Hipoglicemiantes/efeitos adversos , Obesidade/diagnóstico , Obesidade/tratamento farmacológico , Percepção , Ensaios Clínicos Controlados Aleatórios como Assunto , Método Simples-Cego , Paladar
13.
Medicine (Baltimore) ; 100(25): e26505, 2021 Jun 25.
Artigo em Inglês | MEDLINE | ID: mdl-34160469

RESUMO

ABSTRACT: Despite advances in treatments for diabetes mellitus (DM), severe acute glycemic crises still occur. In this study, the characteristics of patients who were transported to an emergency department due to acute glycemic crises were investigated.We enrolled patients who were transported to our hospital by ambulance due to hypoglycemia or hyperglycemia during the period from January 2015 to December 2019. Initial glucose levels below 70 mg/dL and above 250 mg/dL were defined as hypoglycemia and hyperglycemia, respectively.In the 5-year period, 16,910 patients were transported to our hospital by ambulance. Of those patients, 87 patients (0.51%) were diagnosed with hypoglycemia, 26 patients (0.15%) were diagnosed with hyperglycemia and 1 patient was diagnosed with lactic acidosis. Compared to patients with hypoglycemia, blood urea nitrogen, serum potassium and hemoglobin levels were higher in patients with hyperglycemia. Systolic blood pressure was lower and pulse rate was higher in patients with hyperglycemia, possibly reflecting dehydration in hyperglycemia. Patients with hyperglycemia were younger (63 vs 70 years old, median), more likely to be hospitalized (92.3% vs 23.0%) with poorer prognosis (23.1% vs 4.6%) than those with hypoglycemia. In 64 DM patients with hypoglycemia, 34 patients were treated with insulin and 24 patients were treated with sulfonylurea or glinide, and their medication was often inappropriate. Excessive alcohol intake and malnutrition were the main causes of hypoglycemia in 23 non-DM patients. The main reasons for hyperglycemia were interrupted treatment, forgetting insulin injection and infection.To avoid acute glycemic crises, optimization of anti-DM therapy and education of patients are needed.


Assuntos
Acidose Láctica/epidemiologia , Hospitais Gerais/estatística & dados numéricos , Hiperglicemia/epidemiologia , Hipoglicemia/epidemiologia , Hipoglicemiantes/efeitos adversos , Acidose Láctica/sangue , Acidose Láctica/induzido quimicamente , Acidose Láctica/diagnóstico , Idoso , Idoso de 80 Anos ou mais , Consumo de Bebidas Alcoólicas/efeitos adversos , Consumo de Bebidas Alcoólicas/sangue , Glicemia/análise , Diabetes Mellitus/sangue , Diabetes Mellitus/tratamento farmacológico , Serviço Hospitalar de Emergência/estatística & dados numéricos , Feminino , Hemoglobina A Glicada/análise , Humanos , Hiperglicemia/sangue , Hiperglicemia/induzido quimicamente , Hiperglicemia/diagnóstico , Hipoglicemia/sangue , Hipoglicemia/diagnóstico , Hipoglicemia/etiologia , Japão/epidemiologia , Masculino , Desnutrição/sangue , Desnutrição/complicações , Pessoa de Meia-Idade , Estudos Retrospectivos
14.
Methods Mol Biol ; 2310: 201-246, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34096005

RESUMO

Nonalcoholic fatty liver disease (NAFLD) is one of the most frequent metabolic chronic liver diseases in developed countries and puts the populations at risk of progression to liver necro-inflammation, fibrosis, cirrhosis, and hepatocellular carcinoma. Mitochondrial dysfunction is involved in the onset of NAFLD and contributes to the progression from NAFLD to nonalcoholic steatohepatitis (NASH). Thus, liver mitochondria could become the target for treatments for improving liver function in NAFLD patients. This chapter describes the most important steps used for potential therapeutic interventions in NAFLD patients, discusses current options gathered from both experimental and clinical evidence, and presents some novel options for potentially improving mitochondrial function in NAFLD.


Assuntos
Anti-Inflamatórios/uso terapêutico , Antioxidantes/uso terapêutico , Hipoglicemiantes/uso terapêutico , Cirrose Hepática/tratamento farmacológico , Fígado/efeitos dos fármacos , Mitocôndrias Hepáticas/efeitos dos fármacos , Hepatopatia Gordurosa não Alcoólica/tratamento farmacológico , Animais , Anti-Inflamatórios/efeitos adversos , Antioxidantes/efeitos adversos , Apoptose/efeitos dos fármacos , Humanos , Hipoglicemiantes/efeitos adversos , Mediadores da Inflamação/metabolismo , Fígado/metabolismo , Fígado/patologia , Cirrose Hepática/metabolismo , Cirrose Hepática/patologia , Mitocôndrias Hepáticas/metabolismo , Mitocôndrias Hepáticas/patologia , Hepatopatia Gordurosa não Alcoólica/metabolismo , Hepatopatia Gordurosa não Alcoólica/patologia , Estresse Oxidativo/efeitos dos fármacos , Comportamento de Redução do Risco
15.
Lancet Diabetes Endocrinol ; 9(8): 484-490, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-34153269

RESUMO

BACKGROUND: Diabetes is a major risk factor for erectile dysfunction, however, the effect of GLP-1 receptor agonists on erectile dysfunction is unknown. We aimed to assess the incidence, prevalence, and progression of erectile dysfunction in men treated with dulaglutide compared with placebo, and to determine whether dulaglutide's effect on erectile dysfunction was consistent with its effect on other diabetes-related outcomes. METHODS: The Researching Cardiovascular Events with a Weekly Incretin in Diabetes (REWIND) trial was a double-blind, placebo-controlled randomised trial of the effect of dulaglutide on cardiovascular outcomes. REWIND was done at 371 sites in 24 countries. Men and women aged older than 50 years with type 2 diabetes, who had either a previous cardiovascular event or cardiovascular risk factors, were randomly assigned (1:1) to receive either dulaglutide or placebo. Participating men were offered the opportunity to complete the standardised International Index of Erectile Function (IIEF) questionnaire at baseline, 2 years, 5 years, and study end. We did an exploratory analysis, in which we included participants who completed a baseline and at least 1 follow-up IIEF questionnaire. The primary outcome for these analyses was the first occurrence of moderate or severe erectile dysfunction following randomisation, assessed by the erectile function subscores on IIEF. This analysis was part of the REWIND trial, which is registered with ClinicalTrials.gov, NCT01394952. FINDINGS: Between Aug 18, 2011, and Aug 14, 2013, 3725 (70·1%) of 5312 male participants with a mean age of 65·5 years (SD 6·4 years) were analysed, of whom 1487 (39·9%) had a history of cardiovascular disease, and 2104 (56·5%) had moderate or severe erectile dysfunction at baseline. The incidence of erectile dysfunction following randomisation was 21·3 per 100 person-years in the dulaglutide group and 22·0 per 100 person-years in the placebo group (HR 0·92, 95% CI 0·85-0·99, p=0·021). Men in the dulaglutide group also had a lesser fall in erectile function subscore compared with the placebo group, with a least square mean difference of 0·61 (95% CI 0·18-1·05, p=0·006). INTERPRETATION: Long-term use of dulaglutide might reduce the incidence of moderate or severe erectile dysfunction in men with type 2 diabetes. FUNDING: Eli Lilly and Company.


Assuntos
Doenças Cardiovasculares/epidemiologia , Diabetes Mellitus Tipo 2/tratamento farmacológico , Disfunção Erétil/epidemiologia , Peptídeos Semelhantes ao Glucagon/análogos & derivados , Hipoglicemiantes/efeitos adversos , Fragmentos Fc das Imunoglobulinas/efeitos adversos , Proteínas Recombinantes de Fusão/efeitos adversos , Idoso , Biomarcadores/análise , Glicemia/análise , Doenças Cardiovasculares/induzido quimicamente , Doenças Cardiovasculares/patologia , Diabetes Mellitus Tipo 2/patologia , Método Duplo-Cego , Disfunção Erétil/induzido quimicamente , Disfunção Erétil/patologia , Feminino , Seguimentos , Peptídeos Semelhantes ao Glucagon/efeitos adversos , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico
16.
N Engl J Med ; 385(6): 503-515, 2021 08 05.
Artigo em Inglês | MEDLINE | ID: mdl-34170647

RESUMO

BACKGROUND: Tirzepatide is a dual glucose-dependent insulinotropic polypeptide and glucagon-like peptide-1 (GLP-1) receptor agonist that is under development for the treatment of type 2 diabetes. The efficacy and safety of once-weekly tirzepatide as compared with semaglutide, a selective GLP-1 receptor agonist, are unknown. METHODS: In an open-label, 40-week, phase 3 trial, we randomly assigned 1879 patients, in a 1:1:1:1 ratio, to receive tirzepatide at a dose of 5 mg, 10 mg, or 15 mg or semaglutide at a dose of 1 mg. At baseline, the mean glycated hemoglobin level was 8.28%, the mean age 56.6 years, and the mean weight 93.7 kg. The primary end point was the change in the glycated hemoglobin level from baseline to 40 weeks. RESULTS: The estimated mean change from baseline in the glycated hemoglobin level was -2.01 percentage points, -2.24 percentage points, and -2.30 percentage points with 5 mg, 10 mg, and 15 mg of tirzepatide, respectively, and -1.86 percentage points with semaglutide; the estimated differences between the 5-mg, 10-mg, and 15-mg tirzepatide groups and the semaglutide group were -0.15 percentage points (95% confidence interval [CI], -0.28 to -0.03; P = 0.02), -0.39 percentage points (95% CI, -0.51 to -0.26; P<0.001), and -0.45 percentage points (95% CI, -0.57 to -0.32; P<0.001), respectively. Tirzepatide at all doses was noninferior and superior to semaglutide. Reductions in body weight were greater with tirzepatide than with semaglutide (least-squares mean estimated treatment difference, -1.9 kg, -3.6 kg, and -5.5 kg, respectively; P<0.001 for all comparisons). The most common adverse events were gastrointestinal and were primarily mild to moderate in severity in the tirzepatide and semaglutide groups (nausea, 17 to 22% and 18%; diarrhea, 13 to 16% and 12%; and vomiting, 6 to 10% and 8%, respectively). Of the patients who received tirzepatide, hypoglycemia (blood glucose level, <54 mg per deciliter) was reported in 0.6% (5-mg group), 0.2% (10-mg group), and 1.7% (15-mg group); hypoglycemia was reported in 0.4% of those who received semaglutide. Serious adverse events were reported in 5 to 7% of the patients who received tirzepatide and in 3% of those who received semaglutide. CONCLUSIONS: In patients with type 2 diabetes, tirzepatide was noninferior and superior to semaglutide with respect to the mean change in the glycated hemoglobin level from baseline to 40 weeks. (Funded by Eli Lilly; SURPASS-2 ClinicalTrials.gov number, NCT03987919.).


Assuntos
Diabetes Mellitus Tipo 2/tratamento farmacológico , Polipeptídeo Inibidor Gástrico/administração & dosagem , Peptídeos Semelhantes ao Glucagon/administração & dosagem , Hipoglicemiantes/administração & dosagem , Glicemia/análise , Diabetes Mellitus Tipo 2/sangue , Relação Dose-Resposta a Droga , Esquema de Medicação , Quimioterapia Combinada , Feminino , Polipeptídeo Inibidor Gástrico/efeitos adversos , Receptor do Peptídeo Semelhante ao Glucagon 1/agonistas , Peptídeos Semelhantes ao Glucagon/efeitos adversos , Hemoglobina A Glicada/análise , Humanos , Hipoglicemiantes/efeitos adversos , Hipoglicemiantes/uso terapêutico , Incretinas/uso terapêutico , Injeções Subcutâneas , Masculino , Metformina/uso terapêutico , Pessoa de Meia-Idade , Náusea/induzido quimicamente , Perda de Peso/efeitos dos fármacos
17.
Geriatr Psychol Neuropsychiatr Vieil ; 19(2): 137-147, 2021 Jun 01.
Artigo em Francês | MEDLINE | ID: mdl-34165436

RESUMO

Glucose and sodium tubular reabsorption inhibitors, or gliflozins, are a new therapeutic class. Their novel mechanism of action involves inhibition of a glucose and Na+ reabsorption co-transporter in the renal proximal tubule. They reduce blood glucose levels by reducing renal glucose reabsorption. They therefore cause glycosuria, which constitutes an energy loss and ultimately leads to a weight loss of around 2 to 3 kg. They reduce the sodium load and lower blood pressure. This class improves HbA1c by about 0.7%. Empagliflozin has been shown to reduce all-cause mortality in type 2 diabetic patients at high cardiovascular risk and to reduce episodes of cardiac decompensation and is nephroprotective in diabetic and non-diabetic subjects. Empagliflozin, like other gliflozins, does not induce hypoglycaemia as it does not directly stimulate insulin secretion. Due to the high prevalence of type 2 diabetes, heart failure and renal failure in the elderly, gliflozins will become part of geriatric prescriptions. Their advantages and use must be known, especially as their place will be extended to numerous indications in the field of chronic diseases.


Assuntos
Compostos Benzidrílicos/uso terapêutico , Diabetes Mellitus Tipo 2/tratamento farmacológico , Nefropatias Diabéticas/prevenção & controle , Glucosídeos/uso terapêutico , Hipoglicemiantes/uso terapêutico , Inibidores do Transportador 2 de Sódio-Glicose/uso terapêutico , Idoso , Compostos Benzidrílicos/efeitos adversos , Compostos Benzidrílicos/farmacologia , Glucosídeos/efeitos adversos , Glucosídeos/farmacologia , Humanos , Hipoglicemiantes/efeitos adversos , Hipoglicemiantes/farmacologia , Inibidores do Transportador 2 de Sódio-Glicose/efeitos adversos
18.
Nat Med ; 27(6): 1079-1087, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-34127852

RESUMO

Agonism of the glucagon-like peptide-1 receptor (GLP-1R) results in glycemic lowering and body weight loss and is a therapeutic strategy to treat type 2 diabetes (T2D) and obesity. We developed danuglipron (PF-06882961), an oral small-molecule GLP-1R agonist and found it had comparable efficacy to injectable peptidic GLP-1R agonists in a humanized mouse model. We then completed a placebo-controlled, randomized, double-blind, multiple ascending-dose phase 1 study ( NCT03538743 ), in which we enrolled 98 patients with T2D on background metformin and randomized them to receive multiple ascending doses of danuglipron or placebo for 28 d, across eight cohorts. The primary outcomes were assessment of adverse events (AEs), safety laboratory tests, vital signs and 12-lead electrocardiograms. Most AEs were mild, with nausea, dyspepsia and vomiting most commonly reported. There were no clinically meaningful AEs in laboratory values across groups. Heart rate generally increased with danuglipron treatment at day 28, but no heart-rate AEs were reported. Systolic blood pressure was slightly decreased and changes in diastolic blood pressure were similar with danuglipron treatment at day 28, compared with placebo. There were no clinically meaningful electrocardiogram findings. In this study in T2D, danuglipron was generally well tolerated, with a safety profile consistent with the mechanism of action of GLP-1R agonism.


Assuntos
Diabetes Mellitus Tipo 2/tratamento farmacológico , Receptor do Peptídeo Semelhante ao Glucagon 1/genética , Hipoglicemiantes/administração & dosagem , Obesidade/tratamento farmacológico , Animais , Glicemia/efeitos dos fármacos , Peso Corporal/efeitos dos fármacos , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/genética , Diabetes Mellitus Tipo 2/patologia , Feminino , Receptor do Peptídeo Semelhante ao Glucagon 1/agonistas , Humanos , Hipoglicemiantes/efeitos adversos , Masculino , Metformina/administração & dosagem , Camundongos , Pessoa de Meia-Idade , Obesidade/sangue , Obesidade/genética , Obesidade/patologia
19.
Front Public Health ; 9: 668368, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34164370

RESUMO

Background: Currently, the association between sodium-glucose cotransporter 2 inhibitor (SGLT-2i) and malignancy risk has yet to be fully elucidated. This meta-analysis aimed to determine the relationship between SGLT-2i and malignancy risk in type 2 diabetes (T2D) patients. Methods: We searched PubMed, ScienceDirect, EMBASE, Cochrane Central Register of Controlled Trials, and Web of Science to identify randomized controlled trials (RCTs) published up to August 2020 related to T2D patients treated with SGLT-2i vs. placebo or other hypoglycemic agents. The meta-analysis's primary outcome was malignancies' incidence, and the results were evaluated using risk ratio (RR) and 95% confidence interval (CI). Results: We reviewed 76 articles (77 RCTs), comprising 45,162 and 43,811 patients in SGLT-2i and control groups, respectively. Compared with the control group, SGLT-2i had no significant association with augmented overall malignancy risk in T2D patients (RR = 1.05, 95% CI = 0.97-1.14, P = 0.20), but ertugliflozin may upsurge the risk (RR = 1.80, 95% CI = 1.02-3.17, P = 0.04). Compared with active hypoglycemic agents, dapagliflozin may increase (RR = 2.71, 95% CI = 1.46-6.43, P = 0.02) and empagliflozin may decrease (RR = 0.67, 95% CI = 0.45-0.98, P = 0.04) the malignancy risk. Compared with placebo, empagliflozin may exhibit risk increase (RR = 1.25, 95% CI = 1.05-1.49, P = 0.01), primarily in digestive system (RR = 1.48, 95% CI = 0.99-2.21, P = 0.05). Conclusions: Our results proposed that in diverse comparisons, ertugliflozin and dapagliflozin seemed to increase the malignancy risk in T2D patients. Empagliflozin may cause malignancy risk reduction compared with active hypoglycemic agents but increase overall risk primarily in the digestive system compared with placebo. In short, the relationship between SGLT-2i and malignancy in T2D patients remains unclear.


Assuntos
Diabetes Mellitus Tipo 2 , Neoplasias , Inibidores do Transportador 2 de Sódio-Glicose , Diabetes Mellitus Tipo 2/tratamento farmacológico , Humanos , Hipoglicemiantes/efeitos adversos , Neoplasias/induzido quimicamente , Ensaios Clínicos Controlados Aleatórios como Assunto , Inibidores do Transportador 2 de Sódio-Glicose/efeitos adversos
20.
Rev Med Suisse ; 17(741): 1072-1077, 2021 Jun 02.
Artigo em Francês | MEDLINE | ID: mdl-34077038

RESUMO

SGLT2 inhibitors are more and more prescribed in the treatment of type 2 diabetes. Their cardioprotective and nephroprotective effects make them particularly attractive. However, it is important to be aware of their potential side effects. This article aims to summarize the actual evidence regarding the most studied ones. Euglycemic ketoacidosis, genital infections and hypovolemia have been well described. Evidence is less robust regarding the increased risk of amputations, fractures, urinary tract infection or acute kidney disease. This article also aims to summarize some key messages to discuss with patients, in order to prevent the occurrence of euglycemic ketoacidosis and hypovolemia.


Assuntos
Diabetes Mellitus Tipo 2 , Cetose , Inibidores do Transportador 2 de Sódio-Glicose , Infecções Urinárias , Amputação , Diabetes Mellitus Tipo 2/tratamento farmacológico , Humanos , Hipoglicemiantes/efeitos adversos , Inibidores do Transportador 2 de Sódio-Glicose/uso terapêutico
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