Pharmacy & Therapeutics - September 2008 - (Page 548)

Meeting Highlights American Diabetes Association, 2008 68th Annual Scientific Session This year’s meeting of the ADA in San Francisco saw a record-breaking total of 21,000 attendees.Two clinical trials, ACCORD and VADT, which were designed to see whether intensive treatment to lower blood glucose improved outcomes, are discussed. Also covered in this article is a trial of sitagliptin plus metformin for lowering blood glucose. myocardial infarction (MI) or nonfatal stroke or CV death. The antihyperglycemic formulary in ACCORD included metformin (Glucophage, Bristol-Myers Squibb), rosiglitazone (Avandia, GlaxoSmithKline), glimepiride (Amaryl, SanofiAventis), repaglinide (Prandin, Novo Nordisk), acarbose (Precose, Bayer), insulin glargine (Lantus, Aventis), insulin aspart (NovoLog, Novo Nordisk), 70/30 N, R insulin (Lilly), and exenatide (Byetta, Amylin/Lilly). Compared with the standard-therapy group, the intensive-therapy group had a lower HbA1c goal, more physician visits (every one to two months plus at least one interim call), point-of-care HbA1c assessments, greater use of multiple medications, and greater use of insulin. Analysis of these results, presented by Dr. Gerstein, showed that the intensive glycemia-lowering strategy was associated with more weight gain; significantly higher rates of hypoglycemia requiring any type of assistance (16.2% receiving intensive therapy, 5.1% receiving standard therapy, P < 0.001); or significantly higher rates of hypoglycemia requiring medical assistance (10.5% vs. 3.5%; P < 0.001), with hypoglycemia episodes occurring in a larger number of participants. All-cause mortality was higher by 22% in the intensive-treatment group (1.41% per year vs. 1.14% per year; hazard ratio [HR] = 1.22; P = 0.04). The primary outcome was reported at 6.86% in the intensive group and in 7.23% in the standard group (P = 0.16). Among secondary endpoints, significantly more frequent in the intensive-treatment group were mortality (5.01% vs. 3.96%, respectively; P = 0.04), and death from CVD (2.63% vs. 1.83%; P = 0.02). However, the number of nonfatal MIs was lower in the intensive group than in the standard-treatment group (3.63% vs. 4.59%; P = 0.004). Dr. Gerstein concluded that in this population, a therapeutic strategy that targets HbA1c levels below 6%, compared with levels of 7 to 7.9%, increased mortality over 3.5 years. “There is no significant effect of the glycemic intervention on the primary outcome at this time,” he said. Final ACCORD results are expected to be published in late 2010. Summarizing the overall findings, Dr. Simons said that ACCORD identified a previously unknown harm of intensive glucose lowering in high-risk individuals with type-2 diabetes. She underscored that ACCORD was designed to test a therapeutic strategy, not specific components of the strategy. Numerous factors, she added, differed between the randomized groups. Action to Control Cardiovascular Risk (ACCORD) Trial • John B. Buse, MD, PhD, CDE, Associate Professor; Director, Diabetes Care Center; and Chief, Division of General Medicine and Clinical Epidemiology, University of North Carolina School of Medicine in Chapel Hill, N.C. • Hertzel C. Gerstein, MD, McMaster University and Hamilton Health Services, Ontario, Canada • Denise G. Simons-Morton, MD, PhD, National Institutes of Health, Bethesda, Md. At the forefront of the meeting’s discussion of ACCORD, findings revealed that treating patients to achieve lower glycosylated hemoglobin (HbA1c) goals, long considered a sure benefit, can entail serious risks. In a two-hour review of this trial, Steering Committee Vice-Chair Dr. Buse noted that in January 2008, the decision was made to discontinue the intensiveglycemia-treatment arm. ACCORD investigators had sought to determine whether rates of cardiovascular disease (CVD) events could be reduced in diabetic patients by intensively targeting three important risk factors for CVD: hyperglycemia, dyslipidemia, and hypertension. The specific question to be answered was whether a therapeutic strategy aimed at reducing the glycosylated hemoglobin count (HbA1c) to below 6% would decrease rates of CVD events more than a strategy targeting a count of between 7% and 7.9% (with the expectation of achieving a median of 7.5%) in middle-aged and older type-2 diabetic patients at high risk for a CVD event. The controlled, 2-by-2 factorial multicenter trial randomized 5,128 patients to treatment aimed at achieving intensive glycemic control (HbA1c of below 6%) and 5,123 patients to standard glycemic control (HbA1c of 7% to 7.9%). To be eligible for enrollment, patients had to meet the following criteria: • stable type-2 diabetes for three months or more • HbA1c levels between 7.5% and 9% (with more medications) or 11% or below (with fewer medications) • 40 to 79 years of age with previous CVD events or 55 to 79 years of age with anatomical atherosclerotic CVD • albuminuria • left ventricular hypertrophy or one or more CVD risk factors • a body mass index (BMI) of 45 kg/m2 or below • a creatinine level of 1.5 mg/dL or less The primar y outcome was a first occurrence of nonfatal Veterans Affairs Diabetes Trial (VADT) • William C. Duckworth, MD, Veterans Diabetes Trial CoChair and Professor of Clinical Medicine, University of Arizona, Phoenix, Ariz. • Carlos Abraira, MD, VADT Co-Chair and Professor of Medicine, Miami Veterans Affairs Medical Center, Miami, Fla. VADT was the second major study to suggest that intensive glucose lowering entailed significant risks. The aim of the 548 P&T® • September 2008 • Vol. 33 No. 9

Table of Contents Feed for the Digital Edition of Pharmacy & Therapeutics - September 2008

Pharmacy & Therapeutics - September 2008 Contents Editorial Medication Errors Prescription: Washington New Drugs/Drug News/New Medical Devices Drug Forecast Effect of Prescription Copays on Adherence and Treatment Failure with Oral Antidiabetic Medications Vaccine Declinations Present New Challenges for Public Health Universal Health Care in America Digestive Disease Week and American Diabetes Association Pharmaceutical Approval Update

Pharmacy & Therapeutics - September 2008

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