Your browser doesn't support javascript.
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 30.520
Filtrar
1.
J Environ Pathol Toxicol Oncol ; 38(2): 133-141, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31679276

RESUMO

The current study is a review of the literature on patients with diabetes who are diagnosed with colorectal cancer (CRC), encompassing recent research on CRC and the molecular level changes occurring in these patients on the basis of varying environmental as well as non-environmental factors. It has been noted that nearly 50% of all patients undergo the systemic treatment module; however, most of them exhibit drug resistance. In addition, targeted gene therapy has also been used in treatment but has been found to be effective only in patients with a specified molecular profile (or else this might lead to an increased risk of developing resistant mutations). This has led to increasing interest among researchers in finding innovative treatment options. Metformin, a biguanide, has been widely used in treating diabetes. The drug has been reportedly used in cases of hypothesis-generating retrospective population studies of diabetic patients showing reduced incidence of cancer. Metformin helps in reduction of excess insulin levels that possess various effects on cell signaling and metabolism. Nonetheless, there is need for an in-depth study on its molecular mechanism to fill any existing research gaps.


Assuntos
Antineoplásicos/uso terapêutico , Neoplasias Colorretais/tratamento farmacológico , Hipoglicemiantes/uso terapêutico , Metformina/uso terapêutico , Neoplasias Colorretais/complicações , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/tratamento farmacológico , Humanos , Insulina/efeitos adversos , Transdução de Sinais/efeitos dos fármacos
2.
Orv Hetil ; 160(40): 1591-1602, 2019 Oct.
Artigo em Húngaro | MEDLINE | ID: mdl-31565976

RESUMO

Introduction: Liver cirrhosis (20-25%), hepatocellular carcinoma (1.5-3%), insulin resistance (30-40%) and type 2 diabetes (25-30%) are common complications in patients with chronic hepatitis C virus (HCV) infection; however, data are missing from Hungary. Aim: To determine the prevalence of diabetes and insulin resistance in Hungarian HCV patients; to evaluate treatment-induced metabolic changes in relation to diabetes/insulin resistance and virological response and to perform a sustained follow-up for hepatocellular carcinoma detection. Method: We enrolled 150 Hungarian HCV genotype 1 patients (mean age: 48.55 ± 8.55 years, male/female ratio: 45/55%) from 2007-2012. We analysed their baseline, week 12, and end of therapeutic follow-up (24 weeks after interferon-based therapy completion) laboratory data. We performed a 5-year follow-up (2012-2017). Results: The prevalence of insulin sensitivity, insulin resistance and diabetes was 37.4%, 35.3% and 27.3%, respectively. Insulin resistant and diabetic patients showed a decrease in fasting glucose from baseline to end of follow-up (5.47 ± 0.66 vs. 5.08 ± 0.60, p<0.001; 7.90 ± 2.67 vs. 7.04 ± 2.75, p = 0.006), as did both the sustained responder and non-responder groups. Treatment efficacy rate was poor in diabetic vs. insulin sensitive and insulin resistant groups (17% vs. 46% and 40%); insulin sensitivity was not a predictor of virological response. Three participants with diabetes were diagnosed with hepatocellular carcinoma during follow-up by regular ultrasound examinations. Conclusion: Hungarian HCV patients showed high prevalence of diabetes and insulin resistance, though antiviral therapy caused favourable changes in their carbohydrate metabolism. Antiviral therapy was less effective in diabetic patients. Follow-up ultrasound examinations are required for hepatocellular carcinoma in HCV patients, especially those with diabetes. Orv Hetil. 2019; 160(40): 1591-1602.


Assuntos
Antivirais/uso terapêutico , Glicemia/metabolismo , Carcinoma Hepatocelular/complicações , Diabetes Mellitus Tipo 2/epidemiologia , Hepatite C Crônica/complicações , Hepatite C Crônica/terapia , Resistência à Insulina , Neoplasias Hepáticas/complicações , Adulto , Idoso , Complicações do Diabetes/terapia , Diabetes Mellitus Tipo 2/tratamento farmacológico , Feminino , Hepacivirus/efeitos dos fármacos , Hepatite C Crônica/tratamento farmacológico , Hepatite C Crônica/virologia , Humanos , Hungria/epidemiologia , Cirrose Hepática/complicações , Cirrose Hepática/epidemiologia , Neoplasias Hepáticas/epidemiologia , Masculino , Pessoa de Meia-Idade , Prevalência
3.
Medicine (Baltimore) ; 98(41): e17371, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31593087

RESUMO

Rheumatoid arthritis (RA) is a chronic, systemic, inflammatory autoimmune disease associated with increased prevalence of type 2 diabetes mellitus (T2DM). Here, we investigated the effect of the combination of cyclooxygenase (COX)-2 inhibitors and metformin on the rate of admission in patients with RA and T2DM and compared it with that of only COX-2 inhibitors.In total, 1268 subjects with RA and T2DM under COX-2 inhibitor and metformin therapy were selected from the National Health Insurance Research Database of Taiwan, along with 2536 patients as 1:2 sex-, age-, and index year-matched controls without metformin therapy. Cox proportional hazard analysis was used to compare the rate of admission during the 10 years of follow-up.At the end of the follow-up, 72 enrolled subjects (1.89%) had admission, including 9 from the combination group (0.71%) and 63 from the COX-2 inhibitor group (2.48%). The combination group was associated with a lower rate of admission at the end of follow-up (P < .001). Cox proportional hazard regression analysis revealed the lower rate of admission for subjects under combination therapy (adjusted hazard ratio of 0.275; 95% confidence interval = 0.136-0.557, P < .001).Patients with RA and T2DM receiving the combination of COX-2 inhibitors and metformin were associated with lower admission rate than those on COX-2 inhibitors alone, and this effect may be attributed to the decrease in the levels of proinflammatory factors.


Assuntos
Artrite Reumatoide/tratamento farmacológico , Inibidores de Ciclo-Oxigenase 2/administração & dosagem , Diabetes Mellitus Tipo 2/tratamento farmacológico , Hospitalização/estatística & dados numéricos , Hipoglicemiantes/administração & dosagem , Metformina/administração & dosagem , Idoso , Artrite Reumatoide/complicações , Bases de Dados Factuais , Diabetes Mellitus Tipo 2/complicações , Quimioterapia Combinada , Feminino , Humanos , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Modelos de Riscos Proporcionais , Estudos Retrospectivos , Fatores de Risco , Taiwan/epidemiologia
5.
J Assoc Physicians India ; 67(10): 14-19, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31571445

RESUMO

Background: Teneligliptin is widely prescribed dipeptidyl peptidase-4 inhibitor (DPP-4i) in India because of its economical pricing. However, there is no headto-head trial comparing teneligliptin with any other DPP-4i in Indian setting. We evaluated the efficacy and safety of teneligliptin versus sitagliptin as add-on to metformin and/or sulfonylureas in patients with type 2 diabetes mellitus (T2DM). Methods: This prospective, open-label, randomized, active-controlled study enrolled 76 patients (1:1) at 2 centres. Patients received teneligliptin 20 mg or sitagliptin 100 mg orally once daily for 12 weeks as add-on to ongoing metformin or sulfonylurea therapy. Primary endpoint was mean change in glycosylated hemoglobin (HbA1c) from baseline at week 12. Results: Both arms were comparable (p>0.05) at baseline in terms of age, gender, metformin daily dose, sulfonylurea use, HbA1c, fasting and postprandial blood glucose (FBG and PPBG). At the end of 12 weeks, statistically significant reductions were observed in both teneligliptin and sitagliptin arms in HbA1c (-1.19 ± 1.16% p<0.0001 and -0.92 ± 0.95%, p<0.0001), in FBG (-28.3 ± 63.0 mg/dL, p= 0.01 and -22.9 ± 47.4 mg/dL, p=0.006) and PPBG (-41.3 ± 85.4 mg/dL, p=0.006 and -54.7 ± 85.6 mg/dL, p=0.0005). The reductions in all glycemic parameters were similar between the arms. Both gliptins were well-tolerated with no difference in the number of adverse events. There was no change in QT/QTc intervals or other ECG parameters at week 12 in both arms. In post-hoc comparison, percentage of patients achieving target HbA1c <7% (as per American Diabetes Association guidelines) at week 12 favored teneligliptin arm over sitagliptin arm (33.3% vs. 19.4% patients). Conclusion: Teneligliptin provided similar glycemic control as compared to sitagliptin and reduced HbA1c, FBG and PPBG values significantly within 12 weeks of treatment. Both gliptins were found to be safe and well-tolerated in Indian patients with T2DM.


Assuntos
Diabetes Mellitus Tipo 2/tratamento farmacológico , Inibidores da Dipeptidil Peptidase IV/uso terapêutico , Hipoglicemiantes/uso terapêutico , Pirazóis/uso terapêutico , Fosfato de Sitagliptina/uso terapêutico , Tiazolidinas/uso terapêutico , Método Duplo-Cego , Quimioterapia Combinada , Humanos , Índia , Estudos Prospectivos
6.
J Assoc Physicians India ; 67(10): 36-38, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31571450

RESUMO

Objective: Canagliflozin, a sodium glucose co-transporter 2 (SGLT2) inhibitor, has been associated with HbA1c reduction and weight loss in a broad range of patients with type 2 diabetes mellitus (T2DM). This analysis evaluated changes in HbA1c and body weight in patients who were inadequately responding to maximum dose of three oral hypoglycemic agents and reluctant to take insulin therapy. Methods: In this open label interventional single arm study, patients aged 18 to 65 years (N=118) received Canagliflozin 100 mg for in addition to an ongoing triple drug oral hypoglycemic agents (OHA) regimen for a period of 12 weeks. The said population was inadequately responding to maximum dose of three oral hypoglycemic agents and was reluctant to take insulin therapy. Percent change from baseline in HbA1c and body weight was evaluated in the study. Results: Canagliflozin 100 mg additional dose above a triple OHA provided significant HbA1c reduction by 1.9% and weight reduction by 3.01kg over 12 weeks from baseline. Canagliflozin was generally well tolerated, with 2.54% of the patient population reporting Urinary tract infection (UTI) who were withdrawn from study and given appropriate treatment. Conclusion: Canagliflozin 100 mg (One tablet) administered to patients in addition to the inadequately controlled triple drug OHAs who were reluctant for an insulin therapy provided a significant reduction in HbA1c and body weight over 12 weeks. Canagliflozin a SGLT 2 inhibitor is a promising new drug in patients with T2DM in patients who are inadequately controlled on triple therapy and are reluctant to insulin therapy.


Assuntos
Canagliflozina/uso terapêutico , Diabetes Mellitus Tipo 2/tratamento farmacológico , Inibidores do Transportador 2 de Sódio-Glicose/uso terapêutico , Adolescente , Adulto , Idoso , Humanos , Hipoglicemiantes , Pessoa de Meia-Idade , Adulto Jovem
7.
Curr Top Med Chem ; 19(16): 1436-1444, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31512997

RESUMO

Type 2 diabetes is a major health issue worldwide with complex metabolic and endocrine abnormalities. Hyperglycemia, defects in insulin secretion and insulin resistance are classic features of type 2 diabetes. Insulin signaling regulates metabolic homeostasis by regulating glucose and lipid turnover in the liver, skeletal muscle and adipose tissue. Major treatment modalities for diabetes include the drugs from the class of sulfonyl urea, Insulin, GLP-1 agonists, SGLT2 inhibitors, DPP-IV inhibitors and Thiazolidinediones. Emerging antidiabetic therapeutics also include classes of drugs targeting GPCRs in the liver, adipose tissue and skeletal muscle. Interestingly, recent research highlights several shared intermediates between insulin and GPCR signaling cascades opening potential novel avenues for diabetic drug discovery.


Assuntos
Diabetes Mellitus Tipo 2/tratamento farmacológico , Descoberta de Drogas , Hipoglicemiantes/farmacologia , Receptor de Insulina/antagonistas & inibidores , Receptores Acoplados a Proteínas-G/antagonistas & inibidores , Transdução de Sinais/efeitos dos fármacos , Animais , Diabetes Mellitus Tipo 2/metabolismo , Humanos , Hipoglicemiantes/química , Receptor de Insulina/metabolismo , Receptores Acoplados a Proteínas-G/metabolismo
8.
Lancet ; 394(10204): 1169-1180, 2019 Sep 28.
Artigo em Inglês | MEDLINE | ID: mdl-31484629

RESUMO

BACKGROUND: Patients with stable coronary artery disease and diabetes with previous percutaneous coronary intervention (PCI), particularly those with previous stenting, are at high risk of ischaemic events. These patients are generally treated with aspirin. In this trial, we aimed to investigate if these patients would benefit from treatment with aspirin plus ticagrelor. METHODS: The Effect of Ticagrelor on Health Outcomes in diabEtes Mellitus patients Intervention Study (THEMIS) was a phase 3 randomised, double-blinded, placebo-controlled trial, done in 1315 sites in 42 countries. Patients were eligible if 50 years or older, with type 2 diabetes, receiving anti-hyperglycaemic drugs for at least 6 months, with stable coronary artery disease, and one of three other mutually non-exclusive criteria: a history of previous PCI or of coronary artery bypass grafting, or documentation of angiographic stenosis of 50% or more in at least one coronary artery. Eligible patients were randomly assigned (1:1) to either ticagrelor or placebo, by use of an interactive voice-response or web-response system. The THEMIS-PCI trial comprised a prespecified subgroup of patients with previous PCI. The primary efficacy outcome was a composite of cardiovascular death, myocardial infarction, or stroke (measured in the intention-to-treat population). FINDINGS: Between Feb 17, 2014, and May 24, 2016, 11 154 patients (58% of the overall THEMIS trial) with a history of previous PCI were enrolled in the THEMIS-PCI trial. Median follow-up was 3·3 years (IQR 2·8-3·8). In the previous PCI group, fewer patients receiving ticagrelor had a primary efficacy outcome event than in the placebo group (404 [7·3%] of 5558 vs 480 [8·6%] of 5596; HR 0·85 [95% CI 0·74-0·97], p=0·013). The same effect was not observed in patients without PCI (p=0·76, pinteraction=0·16). The proportion of patients with cardiovascular death was similar in both treatment groups (174 [3·1%] with ticagrelor vs 183 (3·3%) with placebo; HR 0·96 [95% CI 0·78-1·18], p=0·68), as well as all-cause death (282 [5·1%] vs 323 [5·8%]; 0·88 [0·75-1·03], p=0·11). TIMI major bleeding occurred in 111 (2·0%) of 5536 patients receiving ticagrelor and 62 (1·1%) of 5564 patients receiving placebo (HR 2·03 [95% CI 1·48-2·76], p<0·0001), and fatal bleeding in 6 (0·1%) of 5536 patients with ticagrelor and 6 (0·1%) of 5564 with placebo (1·13 [0·36-3·50], p=0·83). Intracranial haemorrhage occurred in 33 (0·6%) and 31 (0·6%) patients (1·21 [0·74-1·97], p=0·45). Ticagrelor improved net clinical benefit: 519/5558 (9·3%) versus 617/5596 (11·0%), HR=0·85, 95% CI 0·75-0·95, p=0·005, in contrast to patients without PCI where it did not, pinteraction=0·012. Benefit was present irrespective of time from most recent PCI. INTERPRETATION: In patients with diabetes, stable coronary artery disease, and previous PCI, ticagrelor added to aspirin reduced cardiovascular death, myocardial infarction, and stroke, although with increased major bleeding. In that large, easily identified population, ticagrelor provided a favourable net clinical benefit (more than in patients without history of PCI). This effect shows that long-term therapy with ticagrelor in addition to aspirin should be considered in patients with diabetes and a history of PCI who have tolerated antiplatelet therapy, have high ischaemic risk, and low bleeding risk. FUNDING: AstraZeneca.


Assuntos
Doença da Artéria Coronariana/tratamento farmacológico , Diabetes Mellitus Tipo 2/tratamento farmacológico , Inibidores da Agregação de Plaquetas/uso terapêutico , Ticagrelor/uso terapêutico , Idoso , Aspirina/uso terapêutico , Doenças Cardiovasculares/mortalidade , Angiografia Coronária , Ponte de Artéria Coronária , Doença da Artéria Coronariana/complicações , Estenose Coronária/diagnóstico por imagem , Diabetes Mellitus Tipo 2/complicações , Método Duplo-Cego , Quimioterapia Combinada , Feminino , Hemorragia/induzido quimicamente , Humanos , Hipoglicemiantes/uso terapêutico , Masculino , Pessoa de Meia-Idade , Infarto do Miocárdio/epidemiologia , Intervenção Coronária Percutânea , Prevenção Secundária , Acidente Vascular Cerebral/epidemiologia
9.
Medicine (Baltimore) ; 98(36): e17081, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31490412

RESUMO

OBJECTIVE: The purpose of this study was to assess the efficacy and hypoglycemic risk of sitagliptin versus that of GLP-1 receptor agonists in the management of obese/overweight patients with T2DM. METHODS: EMBASE, PubMed, Cochrane Library, and ClinicalTrials.gov were searched; randomized controlled trials comparing the efficacy of sitagliptin versus that of GLP-1 receptor agonists in obese/overweight patients with T2DM were included. The mean BMI of participants for each study was ≥30 kg/m. We conducted a meta-analysis according to the methods specified in the Cochrane Handbook for Systematic Reviews of Interventions. RevMan 5.1 software was used to perform the meta-analysis. The Cochrane Q test and I statistics were used to estimate the heterogeneity among studies. The results are expressed as the mean difference (MD) or risk ratio (RR) with 95% confidence intervals. RESULTS: A total of 8 eligible studies were included in our meta-analysis. Compared with GLP-1 receptor agonists, sitagliptin was less effective at reducing HbA1c (0.42 [0.27, 0.56]), FPG (0.78 [0.36, 1.19]), PPG (2.61 [1.35, 3.87]), and body weight (1.42 [0.71, 2.14]). Conversely, there were no significant differences in SBP reduction (0.38 [-1.14, 1.89]), DBP reduction (-0.30 [-1.00, 0.39]), and hypoglycemic risk (1.09 [0.50, 2.35]). CONCLUSION: For obese/overweight patients, sitagliptin may exert a less potent effect on HbA1C, FPG, PPG, and weight reduction than GLP-1 receptor agonists, but these drugs had a similar efficacy in reducing blood pressure; furthermore, there was no significant difference in hypoglycemic risk.


Assuntos
Diabetes Mellitus Tipo 2/tratamento farmacológico , Hipoglicemiantes/uso terapêutico , Obesidade/complicações , Fosfato de Sitagliptina/uso terapêutico , Glicemia/efeitos dos fármacos , Pressão Sanguínea/efeitos dos fármacos , Peso Corporal/efeitos dos fármacos , Diabetes Mellitus Tipo 2/complicações , Receptor do Peptídeo Semelhante ao Glucagon 1/agonistas , Humanos , Hipoglicemia/induzido quimicamente , Hipoglicemiantes/farmacologia , Fosfato de Sitagliptina/farmacologia
10.
N Engl J Med ; 381(14): 1309-1320, 2019 Oct 03.
Artigo em Inglês | MEDLINE | ID: mdl-31475798

RESUMO

BACKGROUND: Patients with stable coronary artery disease and diabetes mellitus who have not had a myocardial infarction or stroke are at high risk for cardiovascular events. Whether adding ticagrelor to aspirin improves outcomes in this population is unclear. METHODS: In this randomized, double-blind trial, we assigned patients who were 50 years of age or older and who had stable coronary artery disease and type 2 diabetes mellitus to receive either ticagrelor plus aspirin or placebo plus aspirin. Patients with previous myocardial infarction or stroke were excluded. The primary efficacy outcome was a composite of cardiovascular death, myocardial infarction, or stroke. The primary safety outcome was major bleeding as defined by the Thrombolysis in Myocardial Infarction (TIMI) criteria. RESULTS: A total of 19,220 patients underwent randomization. The median follow-up was 39.9 months. Permanent treatment discontinuation was more frequent with ticagrelor than placebo (34.5% vs. 25.4%). The incidence of ischemic cardiovascular events (the primary efficacy outcome) was lower in the ticagrelor group than in the placebo group (7.7% vs. 8.5%; hazard ratio, 0.90; 95% confidence interval [CI], 0.81 to 0.99; P = 0.04), whereas the incidence of TIMI major bleeding was higher (2.2% vs. 1.0%; hazard ratio, 2.32; 95% CI, 1.82 to 2.94; P<0.001), as was the incidence of intracranial hemorrhage (0.7% vs. 0.5%; hazard ratio, 1.71; 95% CI, 1.18 to 2.48; P = 0.005). There was no significant difference in the incidence of fatal bleeding (0.2% vs. 0.1%; hazard ratio, 1.90; 95% CI, 0.87 to 4.15; P = 0.11). The incidence of an exploratory composite outcome of irreversible harm (death from any cause, myocardial infarction, stroke, fatal bleeding, or intracranial hemorrhage) was similar in the ticagrelor group and the placebo group (10.1% vs. 10.8%; hazard ratio, 0.93; 95% CI, 0.86 to 1.02). CONCLUSIONS: In patients with stable coronary artery disease and diabetes without a history of myocardial infarction or stroke, those who received ticagrelor plus aspirin had a lower incidence of ischemic cardiovascular events but a higher incidence of major bleeding than those who received placebo plus aspirin. (Funded by AstraZeneca; THEMIS ClinicalTrials.gov number, NCT01991795.).


Assuntos
Aspirina/uso terapêutico , Doença da Artéria Coronariana/tratamento farmacológico , Diabetes Mellitus Tipo 2/tratamento farmacológico , Inibidores da Agregação de Plaquetas/uso terapêutico , Ticagrelor/uso terapêutico , Idoso , Aspirina/efeitos adversos , Doença da Artéria Coronariana/complicações , Doença da Artéria Coronariana/mortalidade , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/mortalidade , Método Duplo-Cego , Quimioterapia Combinada/efeitos adversos , Feminino , Seguimentos , Hemorragia/induzido quimicamente , Hemorragia/epidemiologia , Hemorragia/mortalidade , Humanos , Incidência , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Infarto do Miocárdio/epidemiologia , Infarto do Miocárdio/prevenção & controle , Inibidores da Agregação de Plaquetas/efeitos adversos , Acidente Vascular Cerebral/epidemiologia , Acidente Vascular Cerebral/prevenção & controle , Ticagrelor/efeitos adversos , Resultado do Tratamento
11.
J Agric Food Chem ; 67(38): 10614-10623, 2019 Sep 25.
Artigo em Inglês | MEDLINE | ID: mdl-31483658

RESUMO

Type 2 diabetes (T2D) is a pandemic disease chiefly characterized by hyperglycemia. In this study, the combination of serum lipidomic and metabolomic approach was employed to investigate the effect of arabinoxylan on type 2 diabetic rats and identify the critical biomarkers of T2D. Metabolomics analysis revealed that branched-chain amino acids, 12α-hydroxylated bile acids, ketone bodies, and several short- and long-chain acylcarnitines were significantly increased in T2D, whereas lysophosphatidylcholines (LPCs) were significantly decreased. Lipidomics analysis indicated T2D-related dyslipidemia was mainly associated with the increased levels of acetylcarnitine, free fatty acids (FFA), diacylglycerols, triacylglycerols, and cholesteryl esters and the decreased levels of some unsaturated phosphatidylcholines (less than 22 carbons). These variations indicated the disturbed amino acid and lipid metabolism in T2D, and the accumulation of incompletely oxidized lipid species might eventually contribute to impaired insulin action and glucose homeostasis. Arabinoxylan treatment decreased the concentrations of 12α-hydroxylated bile acids, carnitines, and FFAs and increased the levels of LPCs. The improved bile acid and lipid metabolism by arabinoxylan might be involved in the alleviation of hypercholesterolemia and hyperlipidemia in T2D.


Assuntos
Anticolesterolemiantes/administração & dosagem , Diabetes Mellitus Tipo 2/tratamento farmacológico , Hipercolesterolemia/tratamento farmacológico , Hiperlipidemias/tratamento farmacológico , Hipoglicemiantes/administração & dosagem , Hipolipemiantes/administração & dosagem , Xilanos/administração & dosagem , Aminoácidos de Cadeia Ramificada/metabolismo , Animais , Ácidos e Sais Biliares/metabolismo , Carnitina/metabolismo , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/metabolismo , Ácidos Graxos não Esterificados/metabolismo , Glucose/metabolismo , Humanos , Hipercolesterolemia/etiologia , Hipercolesterolemia/metabolismo , Hiperlipidemias/etiologia , Hiperlipidemias/metabolismo , Metabolismo dos Lipídeos , Lipídeos/química , Metabolômica , Ratos
12.
J Assoc Physicians India ; 67(8): 60-62, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31562719

RESUMO

Aim: To evaluate the efficacy of DPP-4 inhibitors (DPP-4i) as the fourth drug in Asian Indian type2 DM patients uncontrolled inspite of using at least 3 oral anti diabetic drugs. Methods: A retrospective analysis of 7858 T2DM patients, who received a DPP-4i (Sitagliptin, Vildagliptin, Teneligliptin, Linagliptin and Saxagliptin) as the fourth drug to achieve glycemic control was undertaken. Patients with inadequate glycaemic control despite receiving optimum doses of at least any other three OADs were included in this analysis. Results: Patients were subdivided into 5 groups, based on the DPP-4i used for treatment: Sitagliptin (n=4787), Vildagliptin (n=2205), Teneligliptin (n=775), Linagliptin (n=64) and Saxagliptin (n=27). The mean fasting blood glucose (FPG) was 160.9 ± 20.4 mg/dl and mean post prandial glucose (PPG) was 227.8 ± 26.3 mg/dl. The mean baseline HbA1c was 8.2 ± 1.5 %. The mean duration required to control diabetes with all DPP-4i was 8.2 weeks with significantly lesser time with Sitagliptin (6.8 weeks, p<0.001). 81.5% of the total cases responded to treatment with a DPP-4i (P <0.05). At the end of the monitoring period, there was significant reduction in mean FPG by-28.1 ± 16.1 mg/dL(P=0.001), mean PPG by -55.3 ± 17.0 mg/dL(P=0.001), and mean HbA1c by -1.2 ± 0.7 (P= 0.001). There was no significant difference between the groups with respect to reduction in PPG and HbA1c. Conclusion: DPP-4 inhibitors are effective in achieving desired glycaemic goals even when used as a fourth drug in patients with inadequate glycaemic control despite receiving an optimum dose of at least 3 OADs.


Assuntos
Diabetes Mellitus Tipo 2/tratamento farmacológico , Inibidores da Dipeptidil Peptidase IV/uso terapêutico , Glicemia , Hemoglobina A Glicada , Humanos , Hipoglicemiantes , Índia , Estudos Retrospectivos , Fosfato de Sitagliptina , Resultado do Tratamento
13.
Rev Med Liege ; 74(9): 443-450, 2019 Sep.
Artigo em Francês | MEDLINE | ID: mdl-31486312

RESUMO

Type 2 diabetes (T2D) is an evolving disease that requires therapeutic adjustments to maintain adequate glucose control in the long run. An increasing number of patients with T2D are treated with a metformin plus gliptin (DPP-4 Inhibitor) combination, especially those for whom a sulfonylurea is avoided because of a risk of hypoglycaemia. When this dual metformin-gliptin therapy becomes insufficient to reach or maintain adequate glucose control, three solutions may be considered : the addition of a gliflozin (SGLT2 inhibitor), the replacement of the gliptin by a glucagon-like peptide-1 receptor agonist or the addition of a basal insulin whose posology should be progressively up-titrated according to fasting glycaemia. This article describes the pro and contra arguments of these three therapeutic regimens. According to the recent data of the literature, the triple oral therapy combining metformin, a gliptin and a gliflozin appears to offer a favourable alternative in terms of efficacy, tolerance, ease of use, patient adherence and cost.


Assuntos
Diabetes Mellitus Tipo 2 , Inibidores da Dipeptidil Peptidase IV , Metformina , Inibidores do Transportador 2 de Sódio-Glicose , Glicemia , Diabetes Mellitus Tipo 2/tratamento farmacológico , Quimioterapia Combinada , Humanos , Hipoglicemiantes/uso terapêutico , Metformina/uso terapêutico , Inibidores do Transportador 2 de Sódio-Glicose/uso terapêutico
14.
Rev Med Liege ; 74(9): 488-494, 2019 Sep.
Artigo em Francês | MEDLINE | ID: mdl-31486321

RESUMO

Semaglutide (Ozempic®) is a new once-weekly agonist of glucagon-like peptide-1 receptors (GLP-1 AR) indicated in the treatment of type 2 diabetes (T2D). Phase III clinical trials of the SUSTAIN programme demonstrated both the efficacy and safety of semaglutide in patients with T2D treated by diet and exercise, oral antidiabetic agents or even insulin. Direct and indirect comparative clinical trials showed that semaglutide (subcutaneous 0.5 or 1.0 mg once weekly) exerts a better glucose-lowering activity and a greater weight loss than other GLP-1 AR. Presented as prefilled pens for subcutaneous injection, semaglutide is currently reimbursed in Belgium after failure of antidiabetic therapy including metformin (HbA1c superior to 7,5 % or 58 mmol/mol) in T2D patients with body mass index ? 30 kg/m².


Assuntos
Diabetes Mellitus Tipo 2 , Peptídeos Semelhantes ao Glucagon , Hipoglicemiantes , Bélgica , Diabetes Mellitus Tipo 2/tratamento farmacológico , Receptor do Peptídeo Semelhante ao Glucagon 1 , Peptídeos Semelhantes ao Glucagon/uso terapêutico , Humanos , Hipoglicemiantes/uso terapêutico
15.
Medicina (B Aires) ; 79(4): 241-250, 2019.
Artigo em Espanhol | MEDLINE | ID: mdl-31487242

RESUMO

Type 2 diabetes is a chronic, progressive disease with increasing prevalence and still late diagnostic. This leads to an increase in the incidence of chronic complications, with signifi cantly increasing health costs. There is also a delay in the onset of insulin therapy in patients with type 2 diabetes for causes related to both patients and physicians. Despite advances in treatment, a low proportion of patients achieve adequate glycemic control. The high hypoglycemia prevalence, consequence of insulin, has led to the development of a new generation long-acting basal insulins to achieve a more stable and prolonged action profile, reducing the variability and risk of hypoglycemia. The EDITION program evaluated the efficacy and safety of glargine U300 compared to glargine U100 in patients with type 1 and 2 diabetes at different stages of the disease. Gla-300 is a new formulation of insulin glargine which has a more stable and prolonged pharmacokinetic and pharmacodynamic profile. Gla-300 demonstrated efficacy and tolerability comparable to glargine U100, with a significant decrease in the risk of hypoglycemia, at night and in 24 hours, providing greater flexibility in the injection schedule, with a window of 6 hours. No increase in weight was observed compared to glargine U100. Bright study (2018) compared glargine U300 vs. degludec U100, demonstrating greater benefit in relation to the risk of hypoglycemia with Gla-300 during titration period. Gla-300 is a last-generation basal insulin, available to improve metabolic control, with a lower risk of hypoglycemia.


Assuntos
Diabetes Mellitus Tipo 1/tratamento farmacológico , Diabetes Mellitus Tipo 2/tratamento farmacológico , Hipoglicemiantes/administração & dosagem , Insulina Glargina/administração & dosagem , Insulina Glargina/farmacocinética , Medicina Baseada em Evidências , Humanos , Hipoglicemiantes/efeitos adversos , Hipoglicemiantes/farmacocinética , Insulina Glargina/efeitos adversos
16.
Lancet ; 394(10208): 1519-1529, 2019 10 26.
Artigo em Inglês | MEDLINE | ID: mdl-31542292

RESUMO

BACKGROUND: Early treatment intensification leading to sustained good glycaemic control is essential to delay diabetic complications. Although initial combination therapy has been suggested to offer more opportunities than a traditional stepwise approach, its validity remains to be determined. METHODS: Vildagliptin Efficacy in combination with metfoRmIn For earlY treatment of type 2 diabetes (VERIFY) was a randomised, double-blind, parallel-group study of newly diagnosed patients with type 2 diabetes conducted in 254 centres across 34 countries. The study consisted of a 2-week screening visit, a 3-week metformin-alone run-in period, and a 5-year treatment period, which was further split into study periods 1, 2, and 3. Patients aged 18-70 years were included if they had type 2 diabetes diagnosed within 2 years prior to enrolment, and centrally confirmed glycated haemoglobin A1c (HbA1c) of 48-58 mmol/mol (6·5-7·5%) and a body-mass index of 22-40 kg/m2. Patients were randomly assigned in a 1:1 ratio either to the early combination treatment group or to the initial metformin monotherapy group, with the help of an interactive response technology system and simple randomisation without stratification. Patients, investigators, clinical staff performing the assessments, and data analysts were masked to treatment allocation. In study period 1, patients received either the early combination treatment with metformin (stable daily dose of 1000 mg, 1500 mg, or 2000 mg) and vildagliptin 50 mg twice daily, or standard-of-care initial metformin monotherapy (stable daily dose of 1000 mg, 1500 mg, or 2000 mg) and placebo twice daily. If the initial treatment did not maintain HbA1c below 53 mmol/mol (7·0%), confirmed at two consecutive scheduled visits which were 13 weeks apart, patients in the metformin monotherapy group received vildagliptin 50 mg twice daily in place of the placebo and entered study period 2, during which all patients received the combination therapy. The primary efficacy endpoint was the time from randomisation to initial treatment failure, defined as HbA1c measurement of at least 53 mmol/mol (7·0%) at two consecutive scheduled visits, 13 weeks apart from randomisation through period 1. The full analysis set included patients who received at least one randomised study medication and had at least one post-randomisation efficacy parameter assessed. The safety analysis set included all patients who received at least one dose of randomised study medication. This study is registered with ClinicalTrials.gov, NCT01528254. FINDINGS: Trial enrolment began on March 30, 2012, and was completed on April 10, 2014. Of the 4524 participants screened, 2001 eligible participants were randomly assigned to either the early combination treatment group (n=998) or the initial metformin monotherapy group (n=1003). A total of 1598 (79·9%) patients completed the 5-year study: 811 (81·3%) in the early combination therapy group and 787 (78·5%) in the monotherapy group. The incidence of initial treatment failure during period 1 was 429 (43·6%) patients in the combination treatment group and 614 (62·1%) patients in the monotherapy group. The median observed time to treatment failure in the monotherapy group was 36·1 (IQR 15·3-not reached [NR]) months, while the median time to treatment failure time for those receiving early combination therapy could only be estimated to be beyond the study duration at 61·9 (29·9-NR) months. A significant reduction in the relative risk for time to initial treatment failure was observed in the early combination treatment group compared with the monotherapy group over the 5-year study duration (hazard ratio 0·51 [95% CI 0·45-0·58]; p<0·0001). Both treatment approaches were safe and well tolerated, with no unexpected or new safety findings, and no deaths related to study treatment. INTERPRETATION: Early intervention with a combination therapy of vildagliptin plus metformin provides greater and durable long-term benefits compared with the current standard-of-care initial metformin monotherapy for patients with newly diagnosed type 2 diabetes. FUNDING: Novartis.


Assuntos
Diabetes Mellitus Tipo 2/tratamento farmacológico , Hipoglicemiantes/administração & dosagem , Metformina/administração & dosagem , Vildagliptina/administração & dosagem , Método Duplo-Cego , Quimioterapia Combinada , Feminino , Hemoglobina A Glicada/análise , Humanos , Hipoglicemiantes/efeitos adversos , Masculino , Metformina/efeitos adversos , Pessoa de Meia-Idade , Resultado do Tratamento , Vildagliptina/efeitos adversos
17.
Medicine (Baltimore) ; 98(35): e16947, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31464934

RESUMO

BACKGROUND: The incidence of diabetes mellitus (DM) is increasing year by year, and various complications can endanger the lives of patients. Type 2 diabetes mellitus (T2DM) accounts for more than 90% of DM, most of which is associated with insulin resistance (IR), and IR has been shown to be closely related to the onset of T2DM and the presence of DM complications. Berberine (BBR) has been shown to improve T2DM with IR in a number of ways. In this study, we aim to evaluate the efficacy and safety of BBR in the treatment of T2DM with IR to provide the newest evidence for clinical use. METHODS AND ANALYSIS: Literature research will be divided into 2 parts: electronic search and manual search. We will search PubMed, EMBASE, The Cochrane Library, the China National Knowledge Infrastructure, China Biology Medicine disc, the China Science and Technology Journal database, and the Wanfang database online. We will select the eligible studies published up to June 30, 2019. Dissertations, conference papers, ongoing trials, internal reports, etc., are searched by manual search methods. We use Homeostatic Model Assessment for IR (HOMA-IR) as the primary outcome of T2DM with IR, and we will also focus on the patient's blood glucose levels and all adverse reactions that occur during medication.Two reviewers will read the articles, extract the data information, and assess the risk of bias independently. Data analysis will use the software such as RevMan 5.3.5, ENDNOTE X7, and STATA 13.0. RESULTS: This study will provide a high-quality synthesis of current evidence of BBR for T2DM with IR from several aspects including HOMA-IR, blood glucose levels, and adverse events. CONCLUSION: This systematic review will provide evidence to assess the efficacy and safety of BBR in the treatment of T2DM with IR. ETHICS AND DISSEMINATION: Because all of the data used in this systematic review has been published, ethical approval is not required. TRIAL REGISTRATION NUMBER: PROSPERO CRD42019123225.


Assuntos
Berberina/uso terapêutico , Diabetes Mellitus Tipo 2/tratamento farmacológico , Resistência à Insulina/fisiologia , Projetos de Pesquisa , Berberina/administração & dosagem , Berberina/efeitos adversos , Glicemia , China , Humanos , Ensaios Clínicos Controlados Aleatórios como Assunto
18.
Orv Hetil ; 160(34): 1346-1352, 2019 Aug.
Artigo em Húngaro | MEDLINE | ID: mdl-31423831

RESUMO

Introduction: Some meta-analyses suggested a positive effect of metformin therapy on lipid parameters, but the potential beneficial effect of metformin on cardiovascular risk in type 2 diabetes is not entirely clear. Aim: We investigated the effect of metformin therapy on lipid parameters and cardiovascular risk in patients with type 2 diabetes. Method: In a cross-sectional, monocentric study, 102 patients with type 2 diabetes without lipid-lowering medication were analysed for lipid profile and cardiovascular risk (United Kingdom Prospective Diabetes Study Risk Calculator) depending on metformin therapy. The patients were divided into two subgroups regarding with (n = 52) or without metformin therapy (n = 50). Results: Patients with metformin therapy had significantly lower total cholesterol and LDL cholesterol levels than patients without metformin (p<0.01 and p<0.05). This effect was independent from glucose control. No intrinsic effect of metformin could be found on systolic blood pressure, HDL cholesterol, triglycerides, and long-term cardiovascular risk using a multivariable risk assessment score. Conclusion: Metformin therapy has beneficial effects on cholesterol levels without improving cardiovascular risk in patients with type 2 diabetes. Orv Hetil. 2019; 160(34): 1346-1352.


Assuntos
Doenças Cardiovasculares/prevenção & controle , HDL-Colesterol/efeitos dos fármacos , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/tratamento farmacológico , Hipoglicemiantes/efeitos adversos , Metformina/efeitos adversos , Doenças Cardiovasculares/epidemiologia , Colesterol/sangue , HDL-Colesterol/sangue , Estudos Transversais , Diabetes Mellitus Tipo 2/fisiopatologia , Feminino , Humanos , Hipoglicemiantes/uso terapêutico , Lipídeos/sangue , Metformina/uso terapêutico , Estudos Prospectivos , Fatores de Risco , Reino Unido
19.
Expert Opin Investig Drugs ; 28(9): 741-747, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31398075

RESUMO

Introduction: Type 2 diabetes is a complex metabolic disorder defined by hyperglycemia which occurs because of impaired insulin secretion and sensitivity. There is an ongoing need to develop novel therapies that are effective and safe with minimal side effects and long-term durability. TTP399 is a hepatoselective, glucokinase activator with potential for treating type 2 diabetes. Areas covered: This is a review of the available data regarding the mechanism of action and the pharmacokinetics of TTP399. The efficacy and safety of the drug for treatment of type 2 diabetes will also be examined with an emphasis on the results of a randomized, controlled phase 2 study. Expert opinion: TTP399 could offer significant advantages over currently available therapies for type 2 diabetes. It successfully lowers glucose without side effects such as hypoglycemia, weight gain or dyslipidemia. Larger trials are required to understand long-term efficacy and safety of this medication in various patient populations and to elucidate its effect on the pathologic processes underpinning type 2 diabetes.


Assuntos
Diabetes Mellitus Tipo 2/tratamento farmacológico , Hipoglicemiantes/farmacologia , Animais , Glicemia/efeitos dos fármacos , Diabetes Mellitus Tipo 2/fisiopatologia , Glucoquinase/efeitos dos fármacos , Glucoquinase/metabolismo , Humanos , Hipoglicemia/induzido quimicamente , Hipoglicemiantes/efeitos adversos , Fígado/metabolismo , Ensaios Clínicos Controlados Aleatórios como Assunto
20.
Expert Opin Investig Drugs ; 28(9): 811-820, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31402716

RESUMO

Introduction: More than 424 million adults have diabetes mellitus (DM). This number is expected to increase to 626 million by 2045. The majority (90-95%) of people with DM has type 2-diabetes (T2DM). The continued prevalence of DM and associated complications has prompted investigators to find new therapies. One of the most recent additions to the anti-diabetic armamentarium are inhibitors of sodium-glucose co-transporters 1 and 2 (SGLT1, SGLT2). Areas covered: The authors review the status of SGLT2 inhibitors for the treatment of T2DM and place an emphasis on those agents in early phase clinical trials. Data and information were retrieved from American Diabetes Association, Diabetes UK, ClinicalTrials.gov, PubMed, and Scopus websites. The keywords used in the search were T2DM, SGLT1, SGLT2, and clinical trials. Expert opinion: The benefits of SGLT inhibitors include reductions in serum glycated hemoglobin (HbA1c), body weight, blood pressure and cardiovascular and renal events. However, SGLT inhibitors increase the risk of genitourinary tract infections, diabetic ketoacidosis, and bone fractures. The development of SGLT inhibitors with fewer side effects and as combination therapies are the key to maximizing the therapeutic effects of this important class of anti-diabetic drug.


Assuntos
Diabetes Mellitus Tipo 2/tratamento farmacológico , Transportador 1 de Glucose-Sódio/antagonistas & inibidores , Inibidores do Transportador 2 de Sódio-Glicose/farmacologia , Adulto , Animais , Diabetes Mellitus Tipo 2/fisiopatologia , Desenvolvimento de Medicamentos/métodos , Hemoglobina A Glicada/metabolismo , Humanos , Hipoglicemiantes/efeitos adversos , Hipoglicemiantes/farmacologia , Transportador 1 de Glucose-Sódio/metabolismo , Transportador 2 de Glucose-Sódio/efeitos dos fármacos , Transportador 2 de Glucose-Sódio/metabolismo , Inibidores do Transportador 2 de Sódio-Glicose/efeitos adversos
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA