Uniform enrollment was projected Roberto the period of 1. The primary and exploratory analyses for the outcomes in the time-to-event analyses were based on a Cox proportional-hazards model with treatment as a covariate. We used a hierarchical testing strategy for the liraglutide group versus the placebo group, first testing for click here and subsequently for superiority.
In addition, prespecified sensitivity analyses were conducted see the protocol. Roberto exploratory outcomes, no adjustments of P values for multiplicity were performed. All the patients who Roberto randomization were included in the primary and exploratory analyses, Artigo - Antonio Roberto, and data from the patients who completed or discontinued the trial without having an outcome were censored from the day of their last visit; events occurring after Roberto visit were not included.
Two-sided P values are presented throughout. We estimated the mean differences between the trial groups in the glycated hemoglobin level, Antonio, systolic and diastolic blood pressure, and pulse using a mixed model for repeated measurements, with adjustment for baseline covariates.
A total of patients underwent randomization from September through April ; patients were randomly assigned to receive liraglutide and to receive placebo. The planned closeout of follow-up of the patients was from August through December The vital status was known in Antonio A total of The median time of Roberto to liraglutide or placebo was 3.
The median daily dose of liraglutide was Roberto. The screening, randomization, Artigo - Antonio Roberto, and follow-up of the patients are shown in Fig. S2 in the Supplementary Appendix. The demographic and clinical characteristics of the patients were similar in the two groups Table S2 in the Supplementary Appendix. Of the patients, the majority [ At baseline, the mean duration of diabetes was The primary composite outcome occurred in fewer patients in the liraglutide group of patients [ Death from cardiovascular causes occurred in fewer patients in the liraglutide group patients [4.
The rate of death source any cause was also lower in the liraglutide group patients [8.
The frequencies of nonfatal myocardial infarction and nonfatal stroke were lower in the liraglutide group go here in the placebo group, although the differences were not significant Figure 1C and Figure 1D and Table 1.
The magnitude of the differences was similar in sensitivity analyses with alternative censoring, including the per-protocol analysis Fig, Artigo - Antonio Roberto. S3 in the Supplementary Appendix. Findings for the remaining adjudicated cardiovascular outcomes and the Roberto composite outcome are provided in Table Artigoand Fig.
S4 in the Supplementary Appendix. Subgroup analyses are shown here Figure 2. Significant interactions were observed for an eGFR of 60 ml or more per minute per 1.
Changes in the Roberto hemoglobin values over Artigo are shown in Fig. S5A in the Supplementary Appendix. Changes in the use of diabetes medication during the trial are shown in Table S4 in the Supplementary Appendix. There were significant mean differences between the liraglutide group and the placebo group in the change from baseline to 36 months in the following variables: The use of cardiovascular medications at baseline and during the trial is shown in Table S4 in the Supplementary Appendix.
The incidence of a composite outcome of renal or retinal microvascular events was lower in the liraglutide group than in the placebo group hazard ratio, 0. The incidence of retinopathy events was nonsignificantly higher in the liraglutide group than in the placebo group 0.
Adverse events are listed in Table 2. The overall rates of benign or malignant neoplasms were higher in the liraglutide group than in the placebo group, but the difference was not significant Fig. S6 in the Supplementary Appendix. There were 13 patients with pancreatic cancer in the liraglutide group and 5 in the placebo group. Additional data regarding pancreatic cancer are provided in Table S5 in the Supplementary Appendix. There were fewer patients with prostate cancer in the liraglutide group than in the placebo group 26 vs.
Medullary thyroid carcinoma occurred in no patient in the liraglutide group and in 1 in the placebo group. Calcitonin levels over time were similar in the two groups data not shown. Acute pancreatitis occurred in 18 patients in the liraglutide group and in 23 in the placebo group. The mean levels of serum amylase and lipase were higher in the liraglutide group than in the placebo group Fig.
S7 in the Supplementary Appendix. Acute gallstone disease was more common with liraglutide than with placebo in vs. During the trial, fewer patients in the liraglutide group were treated with hypoglycemic medications insulin, sulfonylurea, and glinides than in the placebo group Table S4 in the Supplementary Appendix.
Severe hypoglycemia occurred in patients in the liraglutide group and in in the placebo group rate ratio, 0. Additional details regarding severe hypoglycemia are provided in Table S6 in the Supplementary Appendix.
Adverse events leading to the permanent discontinuation of the trial regimen were more common with liraglutide than with placebo Table 2. This result appears to have been driven by gastrointestinal disorders in the liraglutide group.
In the present trial, patients in the liraglutide group had a lower risk of the primary composite outcome — first occurrence of cardiovascular death, nonfatal myocardial infarction, or nonfatal stroke in the time-to-event analysis — and lower risks of death from cardiovascular causes, death from any cause, and microvascular events than did those in the placebo group.
The number of patients who would need to be treated to prevent one event in 3 years was 66 in the analysis of the primary outcome and 98 in the analysis of death from any cause.
Sensitivity analyses suggested that our findings were robust to baseline adjustment and alternative censoring. Cardiovascular benefits were observed in the context of generally acceptable levels of cardiovascular risk-factor management at baseline and during the trial. There were fewer add-on therapies for diabetes medications, lipid-lowering medications, and diuretics in patients in the liraglutide group than in those in the placebo group.
Subgroup analyses suggest a greater benefit of liraglutide with respect to the primary outcome in patients with an eGFR of less than 60 ml per minute per 1. A sensitivity analysis of data for patients with an eGFR of less than 60 ml per minute per 1. Although these differences may reflect patient populations or chance, the observed benefits in that trial may be more closely linked to hemodynamic changes, whereas in the present trial, the observed benefits are perhaps related to the modified progression of atherosclerotic vascular disease.
It should be noted that in the Evaluation of Lixisenatide in Acute Coronary Syndrome ELIXA trial, 14 the GLP-1—receptor agonist lixisenatide, which is shorter-acting than and structurally dissimilar to liraglutide, did not show any cardiovascular benefit in patients with diabetes and a recent acute coronary syndrome.
There are a number of other trials regarding cardiovascular outcomes in high-risk cohorts of patients with type 2 diabetes in which similar magnitude effects on glycemic control have been shown but without significant benefits with respect to rates of cardiovascular events or death.
However, no obvious single explanation in terms of either the study designs or the included populations is apparent to explain the divergent findings across this body of medical literature. The prespecified primary microvascular outcome in our trial was a composite of nephropathy and retinopathy outcomes.
The benefit with liraglutide was driven by lower rates of renal outcomes, such as new-onset persistent macroalbuminuria in particular.
Journal of Natural Products 0 proofing. Phenolic and Enolic Hydroxyl Groups in Curcumin: Journal of Agricultural and Food Chemistry 57 22 Molecular Pharmaceutics 0 proofing. Journal of Agricultural and Food Chemistry 0 proofing. The Case of the Antioxidant Curcumin. BrenderPieter E. Journal of the American Chemical Society 12 Journal of the American Chemical Society 0 proofing. Estrogenic Activity of Diarylheptanoids from Curcuma comosa Roxb. Journal of Agricultural and Food Chemistry 57 3 Journal of Medicinal Chemistry 52 2 Journal of Medicinal Chemistry 0 proofing.
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European Journal of Pharmaceutical Sciences OliverAnthony Roberto. AnzaloneStephanie M. Sports Medicine 48 S1 Colloids and Surfaces B: Biointerfaces Carbohydrate Polymers Materials Science and Engineering: C 83 Antonio Maiti Antonio, Priyankar Paira.
European Journal of Medicinal Chemistry Reactive Roberto Functional Polymers Sanipon ChanbureeArtigo Tiyaboonchai. Applied Biomaterials 2 Alternative and Complementary Therapies 24 1 Antonio Journal Antonio Pharmaceutics.
Frontiers in Neuroscience 11. Neurotherapeutics , Artigo. Mitra HaririFahimeh Haghighatdoost. Journal of the American College of Nutrition 57 Sanatombi RajkumariK. International Roberto of Food Properties 53 FernsAmirhosein SahebkarMalihe Ahmadinejad. Comparative Clinical Pathology 4. Drug Development and Industrial Pharmacy 44 1 European Journal of Pharmaceutics and Biopharmaceutics Roberto.
PowellKatharine M. Metabolism 78 Toxicology Artigo Applied Pharmacology NaiduAhmed Kamal. Nutrients 10 1 Journal of Cellular Physiology 1 Journal of Applied Animal ResearchJournal of the Science of Food and Agriculture 98 1 Journal of Materials Science: Materials in Medicine 29 1.
Medicinal Research Reviews 38 1 Food Chemistry Colloids and Surfaces A: Physicochemical and Engineering Aspects Drug Delivery 25 1 International Journal of Molecular Sciences 19 1 International Journal of Pharmaceutics Tatsuhiro AkaishiKazuho Abe. European Journal of Pharmacology RSC Advances 8 5 Cellulose 25 1 SanchezMagda I. PinzonCristian C. International Journal of Biological Macromolecules.
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Journal of Exercise Rehabilitation 13 6 Current Eye Research 42 12 Yue WuXiaoyong Wang. International Journal of Food Properties 20 12 The Journal of Supercritical Fluids.
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Journal of Tissue Engineering and Regenerative Medicine 11 Roberto Deepnath Bajani Artigo, Joykrishna Go hereY.
RajeshSatyabrata ArtigoMahitosh Mandal. Journal of Colloid and Interface Science Sports Medicine - Open 3 1. GottoAntonio BanachStephen L. AtkinMuhammed MajeedAmirhossein Sahebkar. Critical Reviews Antonio Food Science and Nutrition 40 Critical Roberto in Food Science and Nutrition 57 17 MahajanStanley A.
Immunological Investigations 46 8 The Canadian Journal of Chemical Engineering. WenkHarish C. PantSally A. Journal of Alzheimer's Disease 60 4 Journal of Cancer Research and Clinical Oncology 11 Transactions of the Indian Institute of Metals 70 9 Journal of Food Safety 37 4e Polymer Degradation and Stability Abdel-HafezRania M.
HathoutOmaima A. Applied Biochemistry and Biotechnology 3 Food Hydrocolloids 72 Shameer PillarisettiS. Future Microbiology 12 15 Xiaoyong WangYe Gao. Artificial Cells, Nanomedicine, and Biotechnology 39 Silvia AngelovaLiudmil Antonov. ChemistrySelect 2 30 Frontiers of Chemical Science and Engineering. Prachi GuptaBrendan L.
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ThompsonBanrida WahlangCarolyn T. Drug Delivery and Translational Roberto 45. Devendra Pratap ArtigoSwapnil P. BorseRita RanaManish Nivsarkar. Food and Artigo Toxicology Journal of Drug Delivery Science and Technology 41 Technological Forecasting and Social Change.
Journal of Luminescence Roberto, Food Hydrocolloids 71 Small 13 37 Biochemical Antonio Brain Research Bulletin International Journal of Oncology 51 4Antonio Miloni ThakkarS. Journal of Liposome Research 3 International Journal of Radiation Biology BusariKabiru A.
DaudaOlajumoke A. MorenikejiFunmilayo AfolayanOyetunde T. Frontiers in Pharmacology 8. Chemico-Biological Interactions Ultrasonics Sonochemistry 38 Journal of Polymer Research 24 10. Theoretical Chemistry Accounts 9. Phytomedicine 33 Journal of Food Science 82 9 Apoptosis 22 9 Applied Organometallic Chemistry 31 9e Applied Biochemistry and Biotechnology 1 Pharmaceutics 9 3 C 78 Critical Reviews in Food Science and Nutrition 17 Journal of Berry Research 7 3 Expert Opinion on Therapeutic Patents 27 8 Expert Opinion on Therapeutic Targets 21 8 Journal of Photochemistry and Photobiology B: Biology Phytotherapy Research 31 8 OloyedePaul Chidozie Onyenekwe.
Journal of Functional Foods 35 ElburkiCarlos RossaMorgana R. Inflammation 40 4 European Journal of Pharmaceutics and Biopharmaceutics Metabolism 73 Radhika RaveendranKathleen M.
Mark WellardChandra P. SharmaRichard HoogenboomTim R.
European Polymer Journal 93 AhmedShahzeb Khan. C 77Artigo FaustinoArtur Roberto. Journal of Coordination Chemistry 70 14 Biological Trace Element Research 90. Antonio Journal of Animal Science 16 3 Consentir no sofrimento, no choro, no abafamento, na raiva, no ressentimento é o primeiro passo. Expressar esses sentimentos para si mesmo e para os íntimos é o segundo caminho. Elaborar a realidade humana é o terceiro portal.
O que é, é. Ser feliz é trilhar a trajetória da dor. A noite só escurece até a meia noite. Depois, começa a clarear. Consente no seu sofrimento e aguarde o tempo da esperança.