Dr. Rosenstock:CAROLINA is a randomized, double-blind, active-controlled, multicenter clinical trial designed to test the cardiovascular safety of a DDP-4 inhibitor (linagliptin) versus a sulfonylurea (glimepiride). 2 unique CVOTs - CARMELINA ® and CAROLINA ® - have been designed to establish long-term safety of TRAJENTA in a broad range of T2D patients 1,2. CAROLINA is the only active-comparator CV outcomes trial for a dipeptidyl peptidase-4 (DPP-4) inhibitor. 3,4 CAROLINA ® and the CArdiovascular safety and Renal Microvascular outcomE with LINAgliptin in patients with type 2 diabetes at high vascular risk trial (CARMELINA ®) 14,15 provide one of the most comprehensive datasets on the long-term safety of a DPP-4-inhibitor. The CAROLINA trial, also being presented at ADA, is reporting the results of a head-to-head comparison of the cardiovascular safety/efficacy of linagliptin and glimepiride. Patients with type 2 diabetes and elevated cardiovascular risk were randomized to linagliptin 5 mg daily (n = 3,028) versus glimepiride 4 mg daily (n = 3,014). CAROLINA ® and CARMELINA ® make up the two cardiovascular outcome trials for linagliptin, providing one of the most comprehensive datasets on the long-term safety of a DPP-4-inhibitor. The CAROLINA trial showed that the DPP-4 inhibitor linagliptin was noninferior to glimepiride; however, it was not superior. Whatever the fine print may be, the CAROLINA trial has done great service to diabetes care. Diab Vasc Dis Res . Eli Lilly and Boehringer Ingelheim have announced top-line results from the CAROLINA cardiovascular outcome trial, which evaluated the cardiovascular safety of the drug compared to the sulphonylurea glimepiride, on top of standard of care in 6,033 adults with type II diabetes and increased cardiovascular risk or established cardiovascular disease. The trial included adults with early type 2 diabetes: Adults with a median disease duration of 6.2 years who either received no treatment or received one or two glucose-lowering agents, e.g., metf… 3,4 CAROLINA ® and the CArdiovascular safety and Renal Microvascular outcomE with LINAgliptin in patients with type 2 diabetes at high vascular risk trial (CARMELINA ®) 14,15 provide one of the most comprehensive datasets on the long-term safety of a DPP-4-inhibitor. While CARMELINA is the first CVOT to provide evidence in a majority population with prevalent renal risk, further studies with DPP-4 inhibitors would be welcome, and results are expected shortly from the CAROLINA CVOT, which will compare linagliptin with a sulfonylurea as an active comparator . CAROLINA, will be the first DPP-4 inhibitor cardiovascular outcome trial to compare commonly used second line treatments — Tradjenta and the sulfonylurea glimepiride. Clinical Topics: Diabetes and Cardiometabolic Disease, Dyslipidemia, Heart Failure and Cardiomyopathies, Prevention, Lipid Metabolism, Nonstatins, Heart Failure and Cardiac Biomarkers, Smoking, Keywords: Blood Pressure, Cholesterol, LDL, Diabetes Mellitus, Type 2, Dipeptidyl Peptidase 4, Dipeptidyl-Peptidase IV Inhibitors, Hypoglycemia, Metabolic Syndrome X, Metformin, Myocardial Infarction, Primary Prevention, Risk Factors, Smoking, Stroke, Sulfonylurea Compounds, Weight Gain. 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. 2019 Sep 19;322(12):1155-1166. doi: 10.1001/jama.2019.13772. A unique CV outcome trial in T2D, as it also included a key secondary composite kidney endpoint to evaluate the long-term kidney safety of TRAJENTA ®1 The trial involved 6,033 adults with type 2 diabetes observed for a median duration of more than six years. 2 and 3 randomized clinical trials. This site is intended for healthcare professionals only, CREDENCE and CARMELINA trial overview | ADA 2019 | Medicine Matters diabetes | diabetes.medicinematters.com, Canagliflozin may offer renal protection in people with type 2 diabetes and CKD, WATCH: Diabetes expert commentary on the CREDENCE trial, LISTEN: Researcher comment on the CREDENCE trial, LISTEN: A primary care diabetes expert on the CREDENCE trial, LISTEN: A nephrologist discusses the CREDENCE trial, WATCH: Nephrologist Katherine Tuttle shares practice tips with Jay Shubrook, CARMELINA findings confirmed in highest CV risk subgroups, Favorable long-term cardiovascular safety profile of linagliptin in type 2 diabetes, Round-up of the DPP-4 inhibitor CV outcome trials. N Engl J Med 2013; 369: 1317–1326 White WB et al. These trials typically enrolled younger cohorts with relatively recent onset of diabetes and low CV risk. Presenters: Steven E. Kahn, MB, ChB; Nikolaus Marx, MD, FESC, FAHA; Darren K. McGuire, MD, MHSc; Robert D. Toto, MD; Christoph Wanner, MD; Mark E. Cooper, MBBS, PhD. ... (10%) cutoff for accelerated decline. DPP4 Inhibitor Trials: MACE Scirica BM et al. The primary outcome of cardiovascular death, myocardial infarction, or stroke occurred in 11.8% of the linagliptin group compared with 12.0% of the glimepiride group (p for noninferiority < 0.001, p for superiority = 0.76). Previous CV outcome trials of DPP-4 inhibitors have demonstrated a noninferior risk of a composite CV outcome vs. placebo, but not incremental CV efficacy. Effect of linagliptin vs glimepiride on major adverse cardiovascular outcomes in patients with type 2 diabetes: the CAROLINA Randomized Clinical Trial. In brief, CARMELINA was a multicenter, international, randomized, double-blind study in patients with type 2 diabetes at high cardiorenal risk. Among patients with type 2 diabetes and elevated cardiovascular risk, the DPP-4 inhibitor linagliptin was noninferior to the sulfonylurea glimepiride on prevention of major adverse cardiovascular events over a median of 6.3 years. Part of the Springer Nature Group. Lower cost would favor the former category, while less hypoglycemia and weight gain would favor the latter category. Options for a second-line agent include a sulfonylurea or a DPP-4 inhibitor. N Engl J Med 2015; 373: 232-42 2015;12(3):164-174. doi: 10.1177/1479164115570301 PubMed Google Scholar Crossref CAROLINA ® is one of two cardiovascular outcome trials with the DPP-4 inhibitor, linagliptin. CAROLINA is one of two cardiovascular outcome trials with the DPP-4 inhibitor Tradjenta. Marx N, Rosenstock J, Kahn SE, et al. Rationale, design, and baseline characteristics of the CArdiovascular safety and Renal Microvascular outcomE study with LINAgliptin (CARMELINA(®)): a randomized, double-blind, placebo-controlled clinical trial in patients with type 2 diabetes and high cardio-renal risk. The researchers will present these results in full, along with an analysis of outcomes by baseline cardiovascular disease. Generic Trade Name Trial Sitagliptin Januvia TECOS Saxagliptin Onglyza SAVOR-TIMI 53 Alogliptin Nesina EXAMINE Linagliptin Tradjenta CARMELINA DPP4 Inhibitors 7. Online ahead of print. 2018 Mar 14;17(1):39. doi: 10.1186/s12933-018-0682-3. This new data from CAROLINA, along with data from the placebo-controlled cardiovascular outcome trial CARMELINA, expands the evidence and experience with Tradjenta, to provide healthcare professionals with confidence in the long-term safety profile across a broad range of patients with type 2 diabetes." CAROLINA assessed the long-term CV safety profile of linagliptin versus glimepiride in patients with early type 2 diabetes at increased CV risk. In presenting findings from CARMELINA, a randomized controlled CV outcomes trial enrolling 6,979 adults across 605 centers in 27 countries, … Patients were randomised between 2010 and 2012 from approximately 600 trial centres in 43 different countries. N Engl J Med 2013; 369: 1327–1335 Green JB et al. JAMA 2019;322:1155-66. The researchers will present new renal analyses at this year's ADA. Background:Despite having unquestionable glucose lowering efficacy, current guidelines no more favour the uses of sulphonylureas for CV safety concern, except when cost is an issue. It has provided robust proof that two commonly prescribed drugs, linagliptin and glimepiride, can continue to be used for the benefit of persons with diabetes. Objective: To evaluate the effect of linagliptin, a selective DPP-4 inhibitor, on CV outcomes and kidney outcomes in patients with type 2 diabetes at high risk of CV and kidney events. Design and baseline characteristics of the Cardiovascular Outcome Trial of Linagliptin Versus Glimepiride in Type 2 Diabetes (CAROLINA). The CREDENCE primary findings, published in April this year, showed that the sodium-glucose cotransporter 2 (SGLT2) inhibitor canagliflozin significantly reduced the risk for renal failure and cardiovascular disease in people with type 2 diabetes and chronic kidney disease. CARMELINA is one of two cardiovascular outcome trials with the DPP-4 inhibitor Tradjenta. The CARMELINA-COG substudy was an integral part of the CARMELINA trial . These prior trials evaluating DPP-4 inhibitors enrolled limited numbers of patients with concomitant chronic kidney disease, who are at very high CV risk. Update 06-12-2019 | CARMELINA findings confirmed in highest CV risk subgroups. 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