American Diabetes Association (ADA) 75th Scientific Sessions 2015:
Primary Endpoint Met for Trial Evaluating Cardiovascular Outcomes with Sitagliptin (TECOS)
Researchers at the University of Oxford Diabetes Trials Unit (DTU) and the Duke Clinical Research Institute (DCRI) presented results the Trial Evaluating Cardiovascular Outcomes with Sitagliptin (TECOS). Dr. Rury Holman, MB, ChB, Professor of Diabetic Medicine and Director of the University of Oxford DTU led the symposium at the American Diabetes Association’s 75th Scientific Sessions, in Boston, from June 5–9.
TECOS was an event-driven trial conducted in adults with type 2 diabetes and a history of cardiovascular disease in a usual-care setting. The trial was designed to assess the cardiovascular safety of long-term treatment with sitagliptin (Januvia®, Merck & Co., Inc.) when added to existing therapy compared with placebo.
Sitagliptin Was the First Dipeptidyl Peptidase 4 (DPP-4) Inhibitor
Sitagliptin was approved in 2006, concurrently with lifestyle changes, for diabetes. A combined product of sitagliptin and metformin was approved in 2007.
Additional DPP-4 Inhibitors Began to Appear in 2009
The second DPP-4 inhibitor, saxagliptin, was approved in 2009 as both monotherapy and in combination with metformin, a sulfonylurea, or a thiazolidinedione.
Vildagliptin, approved in Europe and Latin America but not the United States (US), also is available in combination with metformin, a sulfonylurea, or a thiazolidinedione. Linagliptin and alogliptin are available in the US and worldwide.
Different in Metabolism but Comparable in Efficacy
The different DPP-4 inhibitors are distinctive in metabolism (saxagliptin and vildagliptin are metabolized in the liver, and sitagliptin is not), excretion, and recommended dosage. They are similar, however, in efficacy (lowering hemoglobin A1C level), safety profile, and patient tolerance.
Time to the First Cardiovascular-Related Death Was the Primary Outcome Measure in TECOS
The primary composite cardiovascular outcome measured was time to the first confirmed event of cardiovascular-related death, nonfatal myocardial infarction, nonfatal stroke, or hospitalization for unstable angina.
TECOS enrolled 14,724 participants from 38 countries between 2008 and 2012. Median follow-up was 3 years.
Sitagliptin Did Not Impact Cardiovascular Risk
Among patients with type 2 diabetes and established cardiovascular disease, the addition of sitagliptin to usual care did not impact the risk for major adverse cardiovascular events, hospitalization for heart failure, or adverse events.
Effects on the Pancreas Were Uncommon and Comparable Between Groups
Concerns about possible links between incretin-based therapies and effects on the pancreas have been raised. In TECOS, acute pancreatitis and pancreatic cancer were uncommon and not statistically significant different between groups. Numerically, in the sitagliptin group, there were more patients with acute pancreatitis and fewer patients with pancreatic cancer than in the placebo group.
Practitioners Can Be Reassured
Professor Rury Holman of Oxford University, Joint Chair of the study, commented, “Results of TECOS provide reassurance that sitagliptin may be used safely to improve blood glucose levels in a diverse group of patients with type 2 diabetes at high cardiovascular risk, without impacting on rates of cardiovascular complications or heart failure.”
Collaboration between Academia and Industry
TECOS was designed, run, and analyzed independently by DTU and DCRI, in an academic collaboration with Merck & Co., Inc. Professor Eric Peterson, DCRI Executive Director at Duke University and Joint Chair of the study, stated, “TECOS is an excellent example of academic and industry collaborative research.”