At trial in the superior court on 10 January 2018, defendant Schramm Median (quartile [Q] 1, Q3) follow-up was 6.3 (5.9, 6.6) years in both the linagliptin and glimepiride groups. Cardiovascular outcome trials in type 2 diabetes and the sulphonylurea controversy: Rationale for the active-comparator CAROLINA trial Julio Rosenstock1, Nikolaus Marx2, Steven E Kahn3,4, Bernard Zinman5,6, John J Kastelein7, John M Lachin8, Erich Bluhmki9, Sanjay Patel10, Odd-Erik Johansen11 and Hans-Jürgen Woerle11 Abstract White  PC, Desai Effect of linagliptin vs placebo on major cardiovascular events in adults with type 2 diabetes and high cardiovascular and renal risk: the CARMELINA randomized clinical trial. Rates of severe hypoglycemic events were 0.07 per 100 participant-years in the linagliptin group and 0.45 per 100 participant-years in the glimepiride group (incidence rate difference, −0.4 [95% CI, −0.5 to −0.3]; HR, 0.15 [95% CI, 0.08-0.29]; P < .001; Table 3), and hospitalization due to hypoglycemia rates were 0.01 per 100 patient-years in the linagliptin group vs 0.18 per 100 patient-years in the glimepiride group (incidence rate difference, −0.2 [95% CI, −0.2 to −0.1]; HR, 0.07 [95% CI, 0.02-0.31]; P < .001; Table 3). The median duration of follow-up was 6.3 years. Dis. § 15A-1431(b) (2017) (“A defendant convicted in the district court before the judge may appeal to the superior court for trial de novo with a jury as provided by law.”). However, all of these trials were and are being conducted in a placebo-controlled setting design with no active comparators. A final follow-up visit was scheduled 30 days after treatment cessation. Chapter Four of the North Carolina Trial Judges' Bench Book District Court: Volume One, Family Law, 2016, a comprehensive legal reference created for North Carolina district court judges that provides summaries of North Carolina law governing cases routinely heard in district court. People’s Alliance PAC 2018 Questionnaire for North Carolina Trial Division Judicial Candidates Please return this completed form along with a resume or biographical statement describing your education, work history, community Analyses were conducted using SAS version 9.4 (SAS Institute). Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01243424. 1, Family Law, 2018 is a comprehensive legal reference created for North Carolina district court judges.It provides summaries of North Carolina law governing cases routinely heard in district court.  SN. Correction: This article was corrected on December 3, 2019, to correct an error in the Table that presented a percentage as 1000% instead of 100% and an error in the Results section that did not include the median (quartile 1, quartile 3) study medication exposure in the linagliptin group. Because of declining numbers of participants at risk, Kaplan-Meier plots were truncated at 6.5 years after randomization. Scirica Currently, 4 large cardiovascular outcome trials have established the cardiovascular safety of DPP-4 inhibitors vs placebo in patients with type 2 diabetes at a high cardiovascular risk,20-23 including the Cardiovascular and Renal Microvascular Outcome Study with Linagliptin (CARMELINA).23 In 2009, when the current trial was designed, sulfonylureas were the most commonly used second-line glucose-lowering agents after metformin, followed by DPP-4 inhibitors, but no head-to-head cardiovascular outcome trial existed for those 2 classes of medications. Genetic markers predicting sulphonylurea treatment outcomes in type 2 diabetes patients: current evidence and challenges for clinical implementation.  N, McGuire Statistical analysis: Kahn, Espeland, Pfarr, Keller, Mattheus, Meinicke, von Eynatten. North Carolina Trial Lawyer based out of Raleigh, Chris Nichols, discusses trials, liens, technology and changes to the law. A Multicentre, International, Randomised, Parallel Group, Double Blind Study to Evaluate Cardiovascular Safety of Linagliptin Versus Glimepiride in Patients With Type 2 Diabetes Mellitus at High Cardiovascular Risk. Rationale and design of the CAROLINA® - cognition substudy: a randomised controlled trial on cognitive outcomes of linagliptin versus glimepiride in patients with type 2 diabetes mellitus. In all controversies at law respecting property, the ancient mode of trial by jury is one of the Terms of Use| Alogliptin after acute coronary syndrome in patients with type 2 diabetes. patient to receive linagliptin or glimepiride placebo over encapsulated tablet Quaque die (QD), patient to receive glimepiride 1-4 mg or linagliptin placebo tablet Quaque die (QD), glimepiride over-encapsulated tablet 1-4 mg QD. The upper limit of the 95.47% CI of the hazard ratio was 1.14, which met the noninferiority criterion of a hazard ratio of less than 1.3. 2013 Jul;8(4):345-349. doi: 10.1586/17446651.2013.811849. The primary outcome was time to first occurrence of cardiovascular death, nonfatal myocardial infarction, or nonfatal stroke with the aim to establish noninferiority of linagliptin vs glimepiride, defined by the upper limit of the 2-sided 95.47% CI for the hazard ratio (HR) of linagliptin relative to glimepiride of less than 1.3. Marx N, Rosenstock J, Kahn SE, Zinman B, Kastelein JJ, Lachin JM, Espeland MA, Bluhmki E, Mattheus M, Ryckaert B, Patel S, Johansen OE, Woerle HJ. 40 Years to 85 Years   (Adult, Older Adult), Birmingham, Alabama, United States, 35235, Birmingham, Alabama, United States, 35242, Montgomery, Alabama, United States, 36106, Clinical Research Advantage, Inc./Rita B. Chuang, MD, LLC, Quality of Life Medical & Research Center, Jonesboro, Arkansas, United States, 72404, Little Rock, Arkansas, United States, 72205, Little Rock, Arkansas, United States, 72211, Bermuda Dunes, California, United States, 92203, Edinger Medical Group and Research Center, Fountain Valley, California, United States, 92708, Clinical Trials of St. Jude Heritage Med. rosiglitazone, pioglitazone, Glucagon-like peptide 1 (GLP-1) analogue/agonists, Dipeptidyl-peptidase IV (DPP-IV) inhibitors or any insulin) prior to informed consent (previous short term use of insulin (up to two weeks) is allowed if taken at least 8 weeks prior informed consent), treatment with any anti-obesity drug less than 3 months before ICF, previous or planned bariatric surgery or intervention, current or planned system corticoid treatment, acute liver disease or impaired hepatic function, pre-planned coronary artery revascularization within 6 months of ICF, known hypersensitivity to any of the components, Inappropriateness of glimepiride treatment for renal safety issues according to local prescribing information, participation in another trail with IMP given 2 months before Investigational Medicinal/Medical Product (IMP) start, pre-menopausal women who are nursing or pregnant or of child-bearing potential and not willing to use acceptable method of birth control, patients considered reliable by the investigator, acute coronary syndrome =< 6 wks before ICF, stroke or Transient Ischemic Attack (TIA) =< 3 months prior to ICF. Description: The goal of the trial was to evaluate the dipeptidyl peptidase-4 (DPP-4) inhibitor linagliptin compared with the sulfonylurea glimepiride among patients with type 2 diabetes and elevated cardiovascular risk. Author Contributions: Drs Rosenstock and Marx had full access to all the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis. Percentage of participants occurrence of at least one of the following adjudicated components of CV death (including fatal stroke and fatal MI), non-fatal MI (excluding silent MI) and non-fatal stroke is presented as secondary CV endpoint. sign up for alerts, and more, to access your subscriptions, sign up for alerts, and more, to download free article PDFs, sign up for alerts, customize your interests, and more, to make a comment, download free article PDFs, sign up for alerts and more, Archives of Neurology & Psychiatry (1919-1959), http://apps.who.int/iris/bitstream/handle/10665/272433/9789241550284-eng.pdf?ua=1, http://bidocs.boehringer-ingelheim.com/BIWebAccess/ViewServlet.ser?docBase=renetnt&folderPath=/Prescribing+Information/PIs/Tradjenta/Tradjenta.pdf, http://www.fda.gov/downloads/drugs/guidancecomplianceregulatoryinformation/guidances/ucm071627.pdf, https://www.accessdata.fda.gov/drugsatfda_docs/nda/2013/204042Orig1s000SumR.pdf, JAMAevidence: The Rational Clinical Examination, JAMAevidence: Users' Guides to Medical Literature, FDA Approval and Regulation of Pharmaceuticals, 1983-2018, Global Burden of Skin Diseases, 1990-2017, Health Care Spending in the US and Other High-Income Countries, Life Expectancy and Mortality Rates in the United States, 1959-2017, Medical Marketing in the United States, 1997-2016, Practices to Foster Physician Presence and Connection With Patients in the Clinical Encounter, US Burden of Cardiovascular Disease, 1990-2016, US Burden of Neurological Disease, 1990-2017, Waste in the US Health Care System: Estimated Costs and Potential for Savings, Register for email alerts with links to free full-text articles. This trial assessed cardiovascular outcomes of linagliptin vs glimepiride (sulfonylurea) in patients with relatively early type 2 diabetes and risk factors for or established atherosclerotic cardiovascular disease. chapter opening 1-5 Table of Contents Chapter 1: Spousal Agreements Meinert Rates of investigator-reported hypoglycemia were 2.3 events per 100 participant-years in the linagliptin group and 11.1 per 100 participant-years in the glimepiride group (incidence rate difference, −8.7 [95% CI, −9.4 to −8.0]; HR, 0.23 [95% CI, 0.21-0.26]; P < .001); rates of moderate or severe hypoglycemic events were 1.4 per 100 participant-years in the linagliptin group and 8.4 per 100 participant-years in the glimepiride group (incidence rate difference, −7.0 [95% CI, −7.6 to −6.5]; HR, 0.18 [95% CI, 0.15-0.21]; P < .001; Figure 4). Role of the Funder/Sponsor: Representatives of Boehringer Ingelheim were involved in the design and conduct of the study; management, analysis, and interpretation of the data; and preparation, review, and approval of the manuscript. All Rights Reserved, Challenges in Clinical Electrocardiography, Clinical Implications of Basic Neuroscience, Health Care Economics, Insurance, Payment, Scientific Discovery and the Future of Medicine, United States Preventive Services Task Force, 2019;322(12):1155-1166. doi:10.1001/jama.2019.13772. Follow-up ended in August 2018. High cardiovascular risk was defined as (1) established atherosclerotic cardiovascular disease (documented ischemic heart disease, cerebrovascular disease, or peripheral artery disease), (2) multiple risk factors (at least 2 of the following: type 2 diabetes duration >10 years, systolic blood pressure >140 mm Hg [or receiving at least 1 blood pressure–lowering treatment], current smoker, low-density lipoprotein cholesterol ≥135 mg/dL [3.5 mmol/L], or receiving lipid-lowering treatment), (3) age at least 70 years, and (4) evidence of microvascular complications (impaired kidney function [estimated glomerular filtration rate of 30-59 mL/min/1.73 m2], urine albumin/creatinine ratio ≥30 μg/mg, or proliferative retinopathy). Diabetologicka ambulancia MUDr. It provides summaries of North Carolina law governing cases There were 19 participants (9 in the linagliptin group and 10 in the glimepiride group) identified to have been enrolled and treated at multiple sites. JAMA. Patients were randomized to receive 5 mg of linagliptin once daily (n = 3023) or 1 to 4 mg of glimepiride once daily (n = 3010) in addition to usual care.  S, Levine Additional sensitivity analyses are described in eAppendix 6 in Supplement 3. Effect of Linagliptin vs Glimepiride on Major Adverse Cardiovascular Outcomes in Patients With Type 2 Diabetes, Figure 1. 4 Criminal cases proceed to the superior court for trial Among adults with relatively early type 2 diabetes and elevated cardiovascular risk, the use of linagliptin compared with glimepiride over a median 6.3 years resulted in a noninferior risk of a composite cardiovascular outcome. Food and refreshments are also provided at no costs. McGuire Sec. 2015 May;12(3):164-74. doi: 10.1177/1479164115570301. Geneva, Switzerland: World Health Organization; 2018. Among adults with relatively early type 2 diabetes and elevated cardiovascular risk, the use of linagliptin compared with glimepiride over a median of 6.3 years resulted in a noninferior risk of a composite cardiovascular outcome. Mortality and cardiovascular risk associated with different insulin secretagogues compared with metformin in type 2 diabetes, with or without a previous myocardial infarction: a nationwide study. First, because the trial recruited participants with relatively early type 2 diabetes and insulin treatment was an exclusion criterion, the results may not necessarily be applicable to patients with more advanced disease. Follow-up ended in August 2018. Baseline Participant Characteristics in a Study of the Effect of Linagliptin vs Glimepiride on Cardiovascular Outcomes in Patients With Type 2 Diabetes, Table 2. – Any party may demand a trial by jury of any issue triable of right by a jury  SK. Change from baseline to final visit in triglycerides is presented as secondary diabetes-related endpoint. Time to first occurrence of 4P-MACE was hierarchically evaluated as the first of the prespecified key secondary end points, followed by analyses of the proportion of patients receiving treatment and maintaining HbA1c of less than or equal to 7.0% at the final follow-up visit who (1) were without the need for rescue medication, did not have any moderate/severe hypoglycemic episodes, and did not have greater than 2% weight gain or (2) were without the need for rescue medication and did not have greater than 2% weight gain between the end of titration and final visit. What is the effect of linagliptin compared with glimepiride on major cardiovascular events in patients with relatively early type 2 diabetes and elevated cardiovascular risk? The prespecified approach for handling missing data are described in the statistical analysis plan (Supplement 2). Call Number: KFS2328 .A52 2008 Publication Date: 2008  OE, Investigators were encouraged to monitor and use additional medication for glycemic control per local guidelines, particularly if HbA1c was greater than 7.5% after the end of the titration phase.  Z. Diabetes Care. CAROLINA ® (CARdiovascular Outcome study of LINAgliptin versus glimepiride in patients with type 2 diabetes) is a multi-national, randomised, double-blind, active-controlled clinical trial that involved 6,033 adults with type 2 1,2 2 Data Sharing Statement: See Supplement 5.  MA, Armstrong Study record managers: refer to the Data Element Definitions if submitting registration or results information. Trials. Adjudication-confirmed hospitalizations for HF, alone or included in composite outcomes with cardiovascular mortality or investigator-reported HF events, were not significantly different between groups (Table 2; eAppendix 9 in Supplement 3). 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