doi: 10.7326/ACPJ201909170-027. n=4401 / 2.6 yr . The trial was stopped early, according to prespecified rules, after a median follow- up of 27 months, because the boundary for an overwhelming benefit with LCZ696 had been crossed. op0019 stable versus tapered and withdrawn treatment with tumor necrosis factor inhibitor in rheumatoid arthritis remission (arctic rewind): a randomised, open-label, phase 4, non-inferiority trial Funding: Drugs. Epub 2019 Jun 9. These findings suggest that weekly subcutaneous dulaglutide reduced total cardiovascular or fatal event burden in people with type 2 diabetes at moderate cardiovascular risk. Investors will also have noted that Trulicity was tested in a large group of patients who had not previously suffered any cardiovascular event, potentially hinting at a protective function. 0001). 2018 Jan;20(1):42-49. doi: 10.1111/dom.13028. Is it time to REWIND the cardiorenal clock in diabetes? Semaglutide, a GLP-1 analogue with an extended half-life of approximately 1 week (which permits once-weekly subcutaneous administration),4 is currently in development but not yet approved for the treatment of type 2 diabetes. Epub 2017 Jul 14. Effect of dulaglutide on cognitive impairment in type 2 diabetes: an exploratory analysis of the REWIND trial. Correspondence. The reconsolidation using rewind study (RETURN): trial protocol. outcomes trials (CVOTs) have been performed in the past 4 years using lixisenatide, liraglutide, semaglutide, ... Dulaglutide: REWIND 9901 5.4 31.5% 66% 66.2 7.2% 32.3 0.88 (0.79 to 0.99) 0.026 Oral semaglutide: PIONEER 6 3183 1.3 84.7% 85% 66.0 8.2% 32.3 0.79 (0.57 to 1.11) 0.17 *Remaining participants with cardiovascular risk factors. Objectives: This is a preliminary efficacy RCT to determine if the Rewind Technique is likely to be a good candidate to test against usual care in a future pragmatic efficacy RCT. versus 663 events) in 9901 persons with type 2 diabetes and either chronic cardiovascular disease or risk factors, and followed during 5.4 years. Lancet . vs placebo (b ut↑ in sl e) SUSTAIN-6 . Clinical Translation of Cardiovascular Outcome Trials in Type 2 Diabetes: Is There More or Is There Less Than Meets the Eye? Among patients with type 2 DM, GLP-1R agonists are beneficial for primary stroke, MACE, and cardiovascular mortality prevention. Study Protocol [PDF] October 5, 2016 Statistical Analysis Plan [PDF] October 6, 2016 More Information. Diabetes Obes Metab. MMW Fortschr Med. 2021 Feb 17. doi: 10.1007/s00125-021-05398-3. The incidence of total expanded MACE or non-cardiovascular deaths in the dulaglutide and placebo groups was 67.1 and 74.7 per 1000 person-years, respectively [absolute reduction = 7.6 per 1000 person-years; conditional time gap HR 0.93 (95% CI, 0.87–0.99) p = 0.023, and proportional means HR 0.90 (95% CI, 0.82–0.99) p = 0.028]. Online ahead of print. Its efficacy and safety in older versus younger patients ha Current and future therapies for type 1 diabetes. The incidence of total MACE or non-cardiovascular deaths in the dulaglutide and placebo groups was 35.8 and 40.3 per 1000 person-years, respectively [absolute reduction = 4.5 per 1000 person-years; conditional time gap HR 0.90 (95% CI, 0.82–0.98) p = 0.020, and proportional means HR 0.89 (95% CI, 0.80–0.98) p = 0.022]. Additional analyses demonstrated that GLP-1R agonists reduced the risk of incident MACE (OR 0.86; 95% CI 0.80–0.92; p < 0.0001; I2 = 0%) among patients with prior history of MI or nonfatal strokes.Conclusions 2 and 3 randomized clinical trials. During the trial there were 1972 MACE or non-cardiovascular deaths and 3673 expanded MACE or non-cardiovascular deaths. Can Pharm J (Ott). Funding: The Rewind trial also puts Trulicity on the front foot with Ozempic, which does not have a cardiovascular benefit claim on its US label. In comparison to placebo, GLP-1R agonists reduced nonfatal strokes (OR 0.84; 95% CI 0.76–0.94, p = 0.002; I2 = 0%) and all strokes (OR 0.84; 95% CI 0.75–0.93, p = 0.001; I2 = 0%) by 16%. Dulaglutide and cardiovascular outcomes in type 2 diabetes (REWIND): a double-blind, randomised placebo-controlled trial. Methods In patients ≥ 50 years with type 2 diabetes and CV disease or risk factors, dulaglutide reduced CV outcomes. 2021 Jan;34(1):7-19. doi: 10.2337/ds20-0016. A stepwise approach for pharmacists: Cardiovascular risk reduction with novel antihyperglycemic agents in patients with type 2 diabetes and atherosclerotic cardiovascular disease. DECLARE-TIMI . Download full-text PDF Read full-text. 8600 Rockville Pike Primary efficacy outcome: time to first occurrence of vascular death, non-fatal myocardial infarction or non-fatal stroke. Clipboard, Search History, and several other advanced features are temporarily unavailable. Nat Rev Cardiol. 2019 Jul 13;394(10193):121-130. doi: 10.1016/S0140-6736(19)31149-3. Rewind puts you in control of your data, allowing you to restore anything from a single image to an entire store. Efficacy and safety of dulaglutide in the treatment of type 2 diabetes: a comprehensive review of the dulaglutide clinical data focusing on the AWARD phase 3 clinical trial program. The protocol of our systematic review and meta-analysis was registered to the PROSPERO database. Gerstein HC, Colhoun HM, Dagenais GR, Diaz R, Lakshmanan M, Pais P, Probstfield J, Botros FT, Riddle MC, Rydén L, Xavier D, Atisso CM, Dyal L, Hall S, Rao-Melacini P, Wong G, Avezum A, Basile J, Chung N, Conget I, Cushman WC, Franek E, Hancu N, Hanefeld M, Holt S, Jansky P, Keltai M, Lanas F, Leiter LA, Lopez-Jaramillo P, Cardona Munoz EG, Pirags V, Pogosova N, Raubenheimer PJ, Shaw JE, Sheu WH, Temelkova-Kurktschiev T; REWIND Investigators. Dulaglutide reduced major adverse cardiovascular events (MACE) in the REWIND Trial. The REWIND trial is the first study to include a majority of participants (69 percent) with no history of cardiovascular disease at enrollment. n=3183 / 1.3 yr. CANVAS . 2020 Jul;19(7):582-590. doi: 10.1016/S1474-4422(20)30173-3. Description: The goal of the trial was to assess the cardiovascular (CV) safety of dulaglutide, a glucagon-like peptide-1 (GLP-1) agonist, in patients with type 2 diabetes mellitus at higher risk for CV events. Eli Lilly and Company. Study design and participants REWIND was a multicentre, randomised, double­blind, placebo­controlled trial done at 371 … The REWIND trial showed that dulaglutide is superior to placebo in improving glycemic control and reducing CV events in patients with type 2 diabetes and higher CV risk. GLP1R agonists: primary cardiovascular prevention and oral administration. The REWIND trial of the GLP-1 receptor agonist dulaglutide had no lower limit to HbA 1c for eligibility and demonstrated equivalent efficacy for reduction of MACE above and below the median HbA 1c of 55 mmol/mol (7.2%) . Optimizing Therapeutic Outcomes With Oral Semaglutide: A Patient-Centered Approach. n=9901 / 5.4 yr. LEADER . The effect of dulaglutide on stroke: an exploratory analysis of the REWIND trial. Regulatory guidance specifies the need to establish the cardiovascular safety of new therapies for type 2 diabetes in order to rule out excess cardiovascular risk.5 The preapproval Trial to Evaluate Cardiovascular and O… Major trial(s) to support findings/Outcomes* REWIND . Bethesda, MD 20894, Copyright These findings were based on a time-to-first-event analysis and preclude relevant information on the burden of total major events occurring during the trial. Unique Identifier NCT01394952). 2016 Nov;32(8):776-790. doi: 10.1002/dmrr.2810. During his formative years in Chicago in the late '70s, Jesse Saunders would blast his homemade remixes on a boombox on the school bus. In this double-blind trial, we randomly assigned patients with type 2 diabetes and high cardiovascular risk to receive liraglutide or placebo. While all participants had CV risk factors, only 31 percent of study participants had established CV disease. INDIANAPOLIS, Nov. 5, 2018 /PRNewswire/ -- Trulicity ® (dulaglutide) significantly reduced major adverse cardiovascular events (MACE), a composite endpoint of cardiovascular (CV) death, non-fatal myocardial infarction (heart attack) or non-fatal stroke, meeting the primary efficacy objective in the precedent-setting REWIND trial. 5% or less (with no lower limit) on stable doses of up to two oral glucose-lowering drugs with or without basal insulin therapy were eligible if their body-mass index (BMI) was at least 23 kg/m 2 . November 5, 2018. Careers. FOIA Three different GLP-1 RAs have been shown to reduce CV outcomes in people with type 2 diabetes at high CV risk with elevated HbA 1c levels. Interpretation: 2019 Jul 13;394(10193):131-138. doi: 10.1016/S0140-6736(19)31150-X. Eli Lilly and Company. Unable to load your collection due to an error, Unable to load your delegates due to an error, Collaborators, Superiority trial. Dulaglutide and cardiovascular outcomes in type 2 diabetes (REWIND): a double-blind, randomised placebo-controlled trial. One of these trials was the Researching cardiovascular Events with a Weekly INcretin in Diabetes (REWIND) trial, in which the addition of a once-weekly subcutaneous injection of dulaglutide (1.5 mg) significantly reduced the hazard of MACE by 12% in 9901 individuals with type 2 diabetes with either chronic CV disease or CV risk factors . 2020 Feb;8(2):106-114. doi: 10.1016/S2213-8587(19)30423-1. 2018 Jan;20(1):42-49. doi: 10.1111/dom.13028. Therefore, the aim of this multicentre, phase 3 randomized controlled trial, was to establish the non-inferiority of the combined resection versus separated resection of the splenic vein in DP procedures. We pooled odds ratios (OR) using random-effect models, and assessed the heterogeneity using Cochran Q and I2 statistics.ResultsWe identified 8 RCTs, comprising 56,251 patients. Please enable it to take advantage of the complete set of features! National Library of Medicine Determined that 9600 patients and 1200 primary outcomes were required to achieve 90% power (alpha = 0.05) All efficacy and safety analysis were performed using the ITT population. The trial had a median follow-up of more than five years, the longest for a CV outcomes trial of a GLP-1 receptor agonist. Indeed, individuals with established CVD were usually excluded. Lancet. Copyright © 2019 Elsevier Ltd. All rights reserved. Epub 2017 Jul 14. Shanmugasundaram M, Pineda JRE, Murugapandian S. Curr Cardiol Rep. 2021 Mar 2;23(4):24. doi: 10.1007/s11886-021-01452-z. Multicenter, randomized, double-blind, placebo-controlled, event-driven trial designed to assess whether once-weekly Trulicity 1.5 mg safely reduces the incidence of cardiovascular (CV) outcomes compared to placebo in adult … Dulaglutide and renal outcomes in type 2 diabetes: an exploratory analysis of the REWIND randomised, placebo-controlled trial. 2020 Dec 10;154(1):30-35. doi: 10.1177/1715163520976149. Would you like email updates of new search results? REWIND is an international, double-blind, randomized controlled trial that enrolled 9,901 patients age 50 and older with type 2 diabetes from 24 countries at 371 care centers. In fact, the risk reduction was the same for both the primary and secondary prevention cohorts, a slightly puzzling finding. These trials typically enrolled younger cohorts with relatively recent onset of diabetes and low CV risk. 2019 Jul 13;394(10193):95-97. doi: 10.1016/S0140-6736(19)31267-X. Laurence Astill Wright, Kali Barawi, Natalie Simon, Catrin Lewis, David Muss, Neil P Roberts, Neil J Kitchiner, Jonathan I Bisson. The trial was stopped early, according to prespecified rules, after a median follow- up of 27 months, because the boundary for an overwhelming benefit with LCZ696 had been crossed. Thus, these studies had low CV event rates, and the events that did … Change from baseline in fasting glucagon was analyzed using an ANCOVA model with last observation carried forward (LOCF) included in treatment, country, SGLT2i dose, metformin use, and baseline HbA1c strata as fixed effects and baseline fasting glucagon as a covariate (with and without post rescue data). BackgroundThe cardiovascular effect of liraglutide, a glucagon-like peptide 1 analogue, when added to standard care in patients with type 2 diabetes, remains unknown. Jendle J, Grunberger G, Blevins T, Giorgino F, Hietpas RT, Botros FT. Diabetes Metab Res Rev. eCollection 2021 Jan-Feb. von Scholten BJ, Kreiner FF, Gough SCL, von Herrath M. Diabetologia. n=10142 / 3.6 yr. CREDENCE . "The REWIND trial was an ambitious study that conclusively assessed the effects of dulaglutide on people with type 2 diabetes both with and without prior cardiovascular disease (CVD)," said Gerstein. vs placebo (PIONEER-6 . Determined that 9600 patients and 1200 primary outcomes were required to achieve 90% power (alpha = 0.05) All efficacy and safety analysis were performed using the ITT population. Incidences were expressed as number per 1000 person-years. Glucose-Lowering Medications and Cardiovascular Outcomes. Affiliations. Canagliflozin and Renal Outcomes in Type 2 Diabetes and Nephropathy, Generalizability of Glucagon-Like Peptide-1 Receptor Agonist Cardiovascular Outcome Trials to the Overall Type 2 Diabetes Population in the United States, Protection against stroke with glucagon‐like peptide 1 receptor agonists: a systematic review and meta‐analysis, GLP-1RAs in type 2 diabetes: Mechanisms that underlie cardiovascular effects and overview of cardiovascular outcome data, SGLT2 inhibitors for primary and secondary prevention of cardiovascular and renal outcomes in type 2 diabetes: a systematic review and meta-analysis of cardiovascular outcome trials, Comparison of the Effects of Glucagon-Like Peptide Receptor Agonists and Sodium-Glucose Co-Transporter 2 Inhibitors for Prevention of MajorAdverse Cardiovascular and Renal Outcomes in Type 2 Diabetes Mellitus: A Systematic Review and Meta-Analysis of Cardiovascular Outcomes Trials, Albiglutide and cardiovascular outcomes in patients with type 2 diabetes and cardiovascular disease (Harmony Outcomes): a double-blind, randomised placebo-controlled trial, Glucagon-like peptide-1 receptor action in the vasculature, Dulaglutide versus insulin glargine in patients with type 2 diabetes and moderate-to-severe chronic kidney disease (AWARD-7): a multicentre, open-label, randomised trial, Pharmacologic Glycemic Management of Type 2 Diabetes in Adults. Gerstein HC, Colhoun, HM, Dagenais, GR, et al. Estudios de variantes genéticas de sistemas asociados a vías metabólicas de la enfermedad cardiovascular en Nefritis Lúpica Pediátrica clase IV. 375 no. Incretin in Diabetes (REWIND) trial was designed to assess whether the addition of dulaglutide to the diabetes medication regimen of middle­aged and older people with type 2 diabetes safely reduces the incidence of cardiovascular outcomes compared with placebo. 49–51 Mortality outcomes in some of these trials are encouraging, yet the results are inconsistent. 2019 Sep 17;171(6):JC27. REWIND is the longest CV outcomes trial in the glucagon-like peptide-1 receptor agonist (GLP-1 RA) class (median follow-up of 5.4 years) and consisted primarily of people without established CV disease. Multicenter, randomized, double-blind, placebo-controlled, event-driven trial designed to assess whether once-weekly Trulicity 1.5 mg safely reduces the incidence of cardiovascular (CV) outcomes compared to placebo in adult … Debate on Insulin vs Non-insulin Use in the Hospital Setting—Is It Time to Revise the Guidelines for the Management of Inpatient Diabetes? Effects of once-weekly exenatide on … Clinical Trial Registration:https://www.clinicaltrials.gouv. This site needs JavaScript to work properly. Superiority trial. Epub 2019 Jun 9. (REWIND) trial of the glucagon-like peptide 1 (GLP-1) receptor agonist dulaglutide 1Department of Medicine, University of North Carolina School of Medicine, Chapel Hill, NC 2Department of Medicine and Diabetes Unit, Massachusetts General Hospital, Boston, MA 3Harvard Medical School, Boston, MA 4Second Medical Department, Aristotle Univer-