The primary outcome will be PTSD symptom severity as measured by the Clinician-Administered PTSD Scale for DSM5 (CAPS-5) at 8 and 16 weeks post-randomisation. ADA 2019 – Rewind makes Lilly’s Trulicity look average, AHA 2020 – sotagliflozin wins come too late for Lexicon, AHA 2018 – Astrazeneca takes heart from partial Farxiga victory, Heart benefit now a baseline for Invokana and all diabetes drugs, ADA – Canvas paints a mixed picture for J&J’s Invokana, 2020 wins top of the froths for biotech stocks, Go or no go? 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 … © 2021 American College of Cardiology Foundation. 4 years. Novo has said it is planning a much bigger CV outcomes study of oral sema, but this would take several years to complete. 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 … Additionally, they highlighted the fact that participants in the REWIND trial were at lower risk of CV events than participants in the previous studies. True, cross-trial comparisons should always be treated with caution. Less than emphatic cardiovascular outcomes data leave Lilly looking vulnerable to Novo Nordisk’s competing drugs. Lancet 2019;394:95-7. We did exploratory analyses of the prospectively defined renal effects of dulaglutide and their relation to glucose and blood pressure lowering within the REWIND trial. Also at ADA, Lilly presented results from an exploratory analysis of Rewind showing that Trulicity reduced renal events by 15% versus placebo. However, the cardiovascular outcomes data were the main event, and Lilly’s stock opened down 2% this morning. The full data were presented yesterday at the ADA meeting in San Francisco and published simultaneously in The Lancet. 49–51 Mortality outcomes in some of these trials are encouraging, yet the results are inconsistent. This study is registered with ClinicalTrials.gov, number NCT01394952. But Lilly could have done with a stronger result in Rewind to stay ahead of the competition. REWIND is the longest cardiovascular outcome trial in the GLP-1 receptor agonist class (median 5.4 years) and consisted primarily of people without established CV disease. Gerstein HC, Colhoun HM, Dagenais GR, et al. Similar results have been noted with other GLP-1 agents as well. November 5, 2018. Methods: 40 participants will be randomised to receive either the Rewind Technique immediately, or after an 8 week wait. Dulaglutide and cardiovascular outcomes in type 2 diabetes (REWIND): a double-blind, randomised placebo-controlled trial. We use cookies on this website. In December 2008, the U.S. Food and Drug Administration issued guidance to the pharmaceutical industry setting new expectations for the development of antidiabetes drugs for type 2 diabetes. Clinical Topics: Diabetes and Cardiometabolic Disease, Dyslipidemia, Heart Failure and Cardiomyopathies, Prevention, Acute Heart Failure, Hypertension, Keywords: Albuminuria, Angina, Unstable, Brain Ischemia, Constriction, Pathologic, Diabetes Mellitus, Type 2, Dyslipidemias, Glomerular Filtration Rate, Glucagon-Like Peptide 1, Hemoglobin A, Glycosylated, Heart Failure, Hyperglycemia, Hypertension, Hypertrophy, Left Ventricular, Hypoglycemic Agents, Myocardial Infarction, Myocardial Ischemia, Metabolic Syndrome X, Obesity, Pancreatic Neoplasms, Pancreatitis, Primary Prevention, Renal Insufficiency, Stroke, Tobacco Use. Lancet. It was billed as one of the big events of this year’s American Diabetes Association meeting. Dulaglutide and renal outcomes in type 2 diabetes: an exploratory analysis of the REWIND randomised, placebo-controlled trial. The prespecified primary microvascular outcome in our trial was a composite of nephropathy and retinopathy outcomes. EMPagliflozin outcomE tRial in Patients With chrOnic heaRt Failure With Preserved Ejection Fraction (EMPEROR-Preserved) The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Only 31 percent of REWIND trial participants had established CV disease. Methods Study design and participants REWIND was a multicentre, randomised, double-blind, These events were seen in 12% of patients in the Trulicity cohort and 13.4% in the placebo group; although Trulicity was deemed superior, Bernstein described the p value of 0.026 as “not overly compelling” and the overall … The primary outcome, CV death, MI, or stroke for dulaglutide vs. placebo, was 12.0% vs. 13.4% (hazard ratio [HR] 0.88, 95% confidence interval [CI] 0.79-0.99; p = 0.026 for superiority) CV death for dulaglutide vs. placebo: 6.4% vs. 7.0% (p = 0.21) Nonfatal MI for dulaglutide vs. placebo: 4.1% vs. 4.3% (p = 0.65) The heterogeneity of patient characteristics and reported renal outcomes, which hinders comparisons between trials and drug classes, is highlighted. Correspondence to: Prof Hertzel C Gerstein, Population Health Research Institute, McMaster University and Hamilton Health Sciences, Hamilton, ON, L8S 4K1, Canada. The primary outcome, CV death, MI, or stroke for dulaglutide vs. placebo, was 12.0% vs. 13.4% (hazard ratio [HR] 0.88, 95% confidence interval [CI] 0.79-0.99; p = 0.026 for superiority). Prof Hertzel C Gerstein, MD . 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. This was not because Rewind was a failure – as previously reported, the trial found a significant reduction in cardiovascular adverse events in patients receiving the drug versus those on placebo. 2019 Jul 13;394(10193):121-130. doi: 10.1016/S0140-6736(19)31149-3. 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. The primary outcome was the first occurrence of the composite endpoint of non-fatal myocardial infarction, non-fatal stroke, or death from cardiovascular causes (including unknown causes), which was assessed in the intention-to-treat population. Against these competitors, Trulicity comes off worse on cardiovascular outcomes. Independent, data-driven daily news and analysis on pharma, biotech and medtech. "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. And Victoza is no longer Trulicity’s most relevant rival – Lilly’s drug is now squaring up against Novo’s newer once-weekly injectable semaglutide, branded Ozempic, and could soon be competing with the Danish group’s even more convenient oral semaglutide, which is set for a US approval decision by September. 11 These drugs reduce hyperglycemia in patients with type 2 diabetes and are also known to cause slight reductions in weight and blood pressure. ACROSS T2D is the global Academy for Cardiovascular Risks, Outcomes and Safety Studies in Type 2 Diabetes (T2D) All rights reserved. Editorial Comment: Verma S, Mazer CD, Perkovic V. Is it time to REWIND the cardiorenal clock in diabetes? Ozempic’s label does not currently include a cardiovascular benefit claim, and oral sema looks unlikely to get one unless Novo can convince the FDA to accept pooled data from Sustain 6 and Pioneer 6. The primary composite outcome (first occurrence of vascular death, non-fatal myocardial infarction or non-fatal stroke) occurred at statistically lower rates in the dulaglutide treatment group compared to placebo. Consistent with the findings from three cardiovascular outcomes trials of other GLP-1 receptor agonists,5, 6, 27, 30 the REWIND trial raises the possibility of a greater effect on stroke than on myocardial infarction. The Researching cardiovascular Events with a Weekly INcretin in Diabetes (REWIND) double blind randomized trial demonstrated that weekly subcutaneous dulaglutide 1.5 mg, a glucagon like peptide-1 receptor agonist, versus matched placebo reduced the first outcome of major adverse cardiovascular event (MACE), cardiovascular death, nonfatal myocardial infarction or nonfatal stroke … The sample size in REWIND is the largest second only to the recently published EXSCEL trial among studies that evaluated antidiabetic medication in CVD outcome. However, pulse can increase with the use of these agents, but in this trial, suggests no adverse CV consequences. In addition, several secondary outcomes were analysed, comprising a composite clinical microvascular outcome which included diabetic retinopathy or renal disease. Dulaglutide and cardiovascular outcomes in type 2 diabetes (REWIND): a double-blind, randomised placebo-controlled trial. Although it also raises the possibility of some geographical variation of effect, this variation loses statistical significance after accounting for the seven subgroups that were assessed … If Lilly can get a cardiovascular claim added to Trulicity’s label on the back of Rewind, which could happen in the first half of next year, the company's chances of fending off Novo will get a boost. This was driven primarily by a reduction in the individual component of non-fatal stroke. Congenital Heart Disease and Pediatric Cardiology, Invasive Cardiovascular Angiography and Intervention, Pulmonary Hypertension and Venous Thromboembolism, CardioSource Plus for Institutions and Practices, Nuclear Cardiology and Cardiac CT Meeting on Demand, Annual Scientific Session and Related Events, ACC Quality Improvement for Institutions Program, National Cardiovascular Data Registry (NCDR), Liraglutide Effect and Action in Diabetes: Evaluation of Cardiovascular Outcome Results, Trial to Evaluate Cardiovascular and Other Long-term Outcomes With Semaglutide in Subjects With Type 2 Diabetes, Evaluation of Lixisenatide in Acute Coronary Syndrome, Exenatide Study of Cardiovascular Event Lowering, Congenital Heart Disease and     Pediatric Cardiology, Invasive Cardiovascular Angiography    and Intervention, Pulmonary Hypertension and Venous     Thromboembolism, Stable doses of two oral glucose-lowering drugs, If age ≥50 years, then had to have concomitant vascular disease (a previous myocardial infarction [MI], ischemic stroke, revascularization, hospital admission for unstable angina, or imaging evidence of myocardial ischemia), If age ≥55 years, then had to have concomitant myocardial ischemia; coronary, carotid, or lower extremity artery stenosis exceeding 50%; left ventricular hypertrophy; estimated glomerular filtration rate (eGFR) <60 ml/min/1.73 m, If age ≥60 years, then had to have ≥2 of the following: tobacco use, dyslipidemia, hypertension, or abdominal obesity, Coronary or cerebrovascular event within the previous 2 months, CV death for dulaglutide vs. placebo: 6.4% vs. 7.0% (p = 0.21), Nonfatal MI for dulaglutide vs. placebo: 4.1% vs. 4.3% (p = 0.65), Nonfatal stroke for dulaglutide vs. placebo: 2.7% vs. 3.5% (p = 0.017), All-cause mortality: 10.8% vs. 12.0% (p = 0.067), Chronic heart failure hospitalization/urgent visit: 4.3% vs. 4.6% (p = 0.46), Composite microvascular outcome (eye or kidney): 18.4% vs. 20.6% (p = 0.002), Severe hypoglycemic event: 1.3% vs. 1.5% (p = 0.38), Acute pancreatitis: 0.5% vs. 0.3% (p = 0.11); pancreatic cancer: 0.4% vs. 0.2% (p = 0.22), Median reduction in hemoglobin A1c: 0.61%, Composite renal outcome (new macroalbuminuria, sustained decline in eGFR ≥30% chronic renal replacement therapy): 17.1% vs. 19.6% (HR 0.85, 95% CI 0.77-0.93; p = 0.0004), New macroalbuminuria: 8.9% vs. 11.3% (p < 0.0001), Sustained decline in eGFR ≥50%: 1.2% vs. 2.2% (p = 0.0002). The primary endpoint of Rewind was the first occurrence of a major cardiovascular outcome, defined as cardiovascular death, non-fatal heart attack, or non-fatal stroke. The Sustain 6 trial of the former did not include a prespecified superiority analysis, while the Pioneer 6 study of the latter did not meet superiority, although it was a small trial and Novo had long played down expectations (Novo’s next big diabetes bet heads to regulators, 26 November 2018). The FREEDOM-CVO and REWIND trials included injection-free GLP-1 RA with osmotic mini-pump and patients without established cardiovascular background respectively, whereas the PIONEER 6 study investigated oral semaglutide. Ongoing cardiovascular and renal outcome studies such as Dapa-CKD, EMPA-KIDNEY, EMPEROR-Preserved and EMPEROR-Reduced are also discussed. And the MACE benefit was driven by a non-fatal stroke; there was no significant reduction in non-fatal heart attack or cardiovascular death with Trulicity.