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| Medical Economics | Drug Topics | Formulary | Contemporary OB/GYN |
 Daily highlights from the American Diabetes Association 70th Scientific Sessions. From June 25-29, the editors of Medical Economics and Advanstar Communications' other primary care and pharmacy publications will bring you the latest news from Orlando. |
Welcome Greetings from the American Diabetes Association’s 70th Scientific Sessions June 30 – Orlando — The editorial staff of Medical Economics brings you daily coverage of breaking news, the latest research findings, and reports of interest to the readers of Medical Economics, Drug Topics, Formulary, and Contemporary OB/GYN. Our five-day coverage of this year’s American Diabetes Association’s 70th Scientific Sessions includes the results of major clinical trials and ongoing news and information of interest to clinicians who treat type 1 and 2 diabetes. BREAKING NEWS Adding fuel to the rosiglitazone fire
“Our observation does not suggest any cardiovascular hazard [associated with rosiglitazone] and may suggest benefit,” Bach said. “For patients similar to those in the BARI study, our data suggest that there may be a lower cardiac event rate with rosiglitazone than without rosiglitazone.” The key result, he said, was a 28% reduction in the rate of death, myocardial infarction, and stroke compared with patients who had no exposure to TZDs during the study. The risk of congestive heart failure rose by a nonsignificant amount. There was also a 45% increase in bone fractures among patients taking rosiglitazone versus patients with no TZD exposure. BARI (Bypass Angioplasty Revascularization Investigation) was a randomized trial of insulin-sensitizing treatment versus insulin-providing treatment in patients with both type 2 diabetes and established coronary artery disease. The original study was conducted between January 2001 and March 2005, with follow-up continuing through November 2008. Initial results of the trial were presented at the ADA Scientific Sessions in 2009. Within the trial population of 2,368 patients, nearly 1,000 patients received rosiglitazone for a total of 3,025 patient-years of exposure, Bach reported. There were fewer than 450 patient-years of exposure to pioglitazone and no comparison of outcomes associated with the 2 drugs. “We concluded that the pioglitazone experience was small enough that it would not provide significant data,” Bach said. Rosiglitazone was the preferred TZD because it was provided free of charge by its manufacturer, GlaxoSmithKline. Primary support for the trial was provided by the National Heart, Lung and Blood Institute and the National Institute of Diabetes and Digestive and Kidney Diseases. Rosiglitazone use was not randomized, Bach said, but was instituted at the discretion of investigators at 49 clinical sites in the United States, Canada, Brazil, Mexico, the Czech Republic, and Austria. He noted that the nonrandom use of rosiglitazone and the potential confounding effects of other medications used by patients cloud the results. So does the study design. “It is a post hoc analysis,” he cautioned, “but it was a trial specifically designed to look at cardiovascular outcomes. The outcomes relative to rosiglitazone are relevant. This is an appropriate addition to the data set.” BARI data will be presented during an FDA hearing on rosiglitazone in mid-July. Intensive glucose control, addition of fibrate to statin, each reduces progression of diabetic retinopathy, but intensive glucose control raises risk of death
The ACCORD (Action to Control Cardiovascular Risk in Diabetes) study was halted prematurely after 3.5 years when an unexpected higher incidence of death in the intensive glucose-lowering strategy (target hemoglobin [Hb] A1c, <6%) compared to the recommended American Diabetes Association target (7%-7.9%) was apparent. All patients in the intensive-lowering arm were then transitioned to the standard-treatment arm for the remainder of the trial’s 5 years. The median HbA1c level before the transition phase was 6.4% in the intensive arm and 7.5% in the standard arm. ACCORD had 3 separate aims: to test whether intensive lowering of blood glucose (HbA1c <6%), intensive lowering of systolic blood pressure to less than 120 mm Hg (vs <140 mm Hg), and treatment of lipids with a combination of a fibrate and simvastatin (vs simvastatin alone) would lower diabetes complications. Progression of diabetic retinopathy measured by fundus photography was assessed in about 3,000 of the study participants (from each of the treatment arms). In the intensive glucose-lowering arm compared with the less-intensive arm, as well as in the fibrate-statin arm compared with the statin- monotherapy arm, progression of diabetic retinopathy was slowed, said Emily Chew, MD, of the Clinical Trials Branch of the Division of Epidemiology and Clinical Applications at the National Eye Institute of the National Institutes of Health. At 4 years, compared with standard blood glucose control, those in the intensively treated arm had a reduction in progression of diabetic retinopathy by about one-third, from 10.4% to 7.3%. Similarly, compared with simvastatin alone, addition of a fibrate to simvastatin reduced progression of diabetic retinopathy by one-third, from 10.2% to 6.5%. There was no difference in the incidence of progression between the 2 blood pressure-lowering arms of ACCORD, said Chew.
The group initially randomized to intensive glucose control had a lower risk of nonfatal myocardial infarction, a trend toward a reduction in the incidence of stroke, and an increase in the rate of cardiovascular death at 5 years, Gerstein said. “Targeting an A1c less than 6% is not better than targeting an A1c of 7% to 7.9% in people with cardiovascular risk factors,” said Gerstein. More from ACCORD: Question of blood pressure target for high-risk type 2 diabetics remains open
In the study, patients randomized to intensive blood pressure lowering who achieved a mean SBP of 119 mm Hg had a 41% reduction in the incidence of stroke compared with those patients with type 2 diabetes who achieved a mean SBP of 134 mm Hg. Nevertheless, because strokes were relatively infrequent in ACCORD, a strategy of intensive blood pressure lowering in patients with type 2 diabetes at high risk of cardiovascular events cannot be recommended at this time. A total of 4,733 patients were randomized into the ACCORD blood pressure trial. There were 208 cardiovascular events in the intensive blood pressure-lowering group compared to 237 in the standard-treatment group. The composite event rate included nonfatal heart attack, nonfatal stroke, or cardiovascular death. The reason for the lack of effect of intensive blood pressure lowering on the composite cardiovascular endpoint was the low total event rate in the study, said Cushman, chief of hypertension, Memphis Veterans Affairs Medical Center, and professor of medicine and preventive medicine, University of Tennessee. “We predicted that the standard group would have an event rate of 4% per year, but they had an event rate of only 2% per year,” he said. He speculated that high use of statins and aspirin in the standard target group might explain the less-than-expected event rate in this group. There was no subgroup that had adverse outcomes with intensive blood pressure lowering, Cushman said, but adverse effects were more frequent in this group, which could be partially explained by the greater number of drugs needed to achieve the lower SBP target. New diagnostic guidelines spur debate The new standards using hemoglobin (Hb) A1c for the diagnosis of diabetes issued in January 2010 have not come without controversy. It is not that HbA1c is incorrect or even inappropriate, said Robert Cohen, MD, professor of medicine, University of Cincinnati College of Medicine, Cincinnati, Ohio. The problem is that HbA1c does not correlate precisely with blood glucose. “The new standards come from glucose levels that have consequences and the A1c that corresponds to those levels,” Cohen reminded a Wednesday-morning symposium, Diabetes Diagnosis Based on the A1c. “The question is how well A1c corresponds to those glucose levels in your patient.” For most people, there is probably not a significant issue, Cohen noted. For the majority of the population, HbA1c does reliably correspond to specific blood glucose levels, but not for all. “Look at your next patient,” Cohen suggested during a talk, Should A 1c Be the Preferred Test to Diagnose Diabetes? “Is that patient in the middle of the crowd and corresponds precisely? Or is that patient one of those for whom an A1c of 6 represents a blood glucose of 130? Or maybe 200? Discordance works both ways. A blood glucose of 130 may represent an A1c of 5.9 or 7.0.” The concordance between blood glucose and HbA1c is only 0.84, Cohen explained. That means some people will fall outside the normal range on one test and within the normal range on the other. Studies suggest that about 10% of the discordance is biologic in origin, most likely genetic. That implies that there are about 2 million patients in the United States alone with a mismatch between their blood glucose and their HbA1c. In another presentation here, the same authors found that telemedicine participants had smaller declines in physical activity over time and a lower rate of physical impairment than the usual-care group. “If you see similar results from blood glucose and A1c, you can have high confidence in the result,” Cohen concluded. “Biologic variability alone could change a 7% to a 6 or an 8, which could change the diagnosis and treatment for your patient.” “A1c is a good test for the diagnosis of diabetes in a large part of the population,” Cohen continued. “I just can’t tell you which part. It is not sufficient on its own to provide a diagnosis for all individuals. We are going to need multiple measures to be sure.” Glycemic control better with a sensor-augmented pump vs multiple daily insulin injections; rate of hypoglycemia is low with the sensor Use of a sensor-augmented pump (SAP) is superior to multiple daily insulin injections in reducing hemoglobin (Hb) A1c levels without an increased risk of hypoglycemia in both adults and children with type 1 diabetes who are not in good control on multiple daily injections, said Richard M Bergenstal, MD. “We are making headway into achieving our goals of better control and less hypoglycemia,” Bergenstal said. He presented the results of a study conducted in 30 countries in which the 2 modes of glycemic control were compared in 485 patients (intent-to-treat population). The sensor also acts as a transmitter to send glucose values every 5 minutes to the pump, which delivers insulin to the patient with input from the patient. Patients were 7 to 70 years old (mean, 32 years), had HbA1c levels between 7.4% and 9.5% (mean, 8.3%), and were being treated with at least 3 injections daily for at least 3 months. Average duration of diabetes was 10 years. The SAP “combines the most advanced technology we have today,” said Bergenstal, executive director of the International Diabetes Center, Park Nicollet, Minneapolis, and president of medicine and science at the American Diabetes Association. Patients assigned to SAP had sequential training in the use of the pump, sensor, and the management software (both groups used management software) over 5 weeks. The findings reported today were results from 1 year. The primary outcome, change in HbA1c level, was significantly better in the SAP group compared with the group administering multiple daily injections (declines of 0.8% vs 0.2%, respectively; P=.001). One-year HbA1c results were superior in the SAP arm in both adults (19 years old or older) and children/adolescents (7 to 18 years old). In the adult group, mean HbA1c was 7.3% in the SAP arm versus 7.9% in the conventionally treated arm; in children/adolescents, mean HbA1c was 7.9% in the SAP arm and 8.5% in the conventional arm. The frequency of sensor use was related to changes in HbA1c: those who used the sensor 80% or more of the time had a decline in HbA1c of a mean of 1.21%; those who used it less than 40% of the time had mean declines in HbA1c of 0.19% to 0.43%. The rates of hypoglycemia (blood glucose <70 mg/dL) decreased slightly in both groups, with no significant difference between groups. Rates of hyperglycemia (blood glucose >180 mg/dL) declined significantly in the SAP arm compared to the arm receiving multiple daily injections (P<.001). There were 13 episodes of severe hypoglycemia per 100 person-years in both treatment arms. The rates of hypoglycemia “were some of the lowest we’ve ever seen in a large, randomized, controlled trial,” said Bergenstal. Community-based lifestyle program helps overweight/obese shed pounds, lower blood glucose A community-based behavioral lifestyle intervention results in significant reductions in hemoglobin (Hb) A1c, fasting blood glucose, and body weight in overweight/obese individuals with prediabetes, said David Goff Jr, MD, PHD. The intervention is managed by registered dietitians (RDs) or certified diabetes educators (CDEs) but delivered by community health workers who are trained by the RDs and CDEs, with further support from digital video discs. The program is similar to the Diabetes Prevention Program, which was conducted in 27 centers around the United States but applied in a community setting. In the Healthy Living Partnerships to Prevent Diabetes (HELP-PD) study, 301 overweight/obese adults 21 years old or older (body mass index [BMI] of 25 to 40 kg/m2) who had 2 fasting glucose levels of 95 to 125 mg/dL were randomized to the intervention or usual care. The goals of the intervention were a calorie deficit of 500 to 1,000 calories per day and 180 minutes of activity per week introduced gradually to affect a weight loss to 1 to 2 lb per week and a 7% loss of body weight by 1 year. The intervention group underwent a 6-month intensive phase of education and meetings with community health workers. The usual care group received 2 sessions with an RD during the first 3 months and monthly newsletters about community resources for weight loss. Three-fourths of the study population was white; one-fourth was black. The average fasting glucose value at baseline was 105.5 mg/dL. Findings at 12 months were:
As ascertained by a single measure of blood glucose, 2 participants in the intervention group progressed to diabetes at month 12 compared with 7 in the usual care group. The trial is ongoing. “The effects during the second year and beyond and the economic impact are still to be determined,” Goff said. Updated diagnosis, drug guidelines in gestational diabetes New data are changing the way gestational diabetes is diagnosed and treated. Veteran diabetes educator Donna Jornsay, RN, BSN, PNP-C, CDE, North Shore-Long Island Jewish Health System, Lake Success, New York, laid out the current guidelines during a Tuesday morning seminar, The Art and Science of Gestational Diabetes Counseling. “Our initial diagnostic criteria for gestational diabetes were used to define who was at risk,” Jornsay explained. “They were not designed to assess perinatal outcomes. That is why the diagnostic criteria have been updated.” The current criteria are based on the HAPO (Hyperglycemia and Adverse Pregnancy Outcomes) trial that was first presented at the ADA Scientific Sessions in 2007. The cutoff for gestational diabetes has been set at either a fasting plasma glucose level of 92, a 1-hour oral glucose tolerance test plasma glucose level of 180, or a 2-hour plasma glucose level of 153. Fasting glucose alone identifies gestational diabetes in about 8.3% of pregnant women. Adding 1-hour plasma glucose identifies 14%, and adding a 2-hour plasma glucose identifies 16.1%. If test results are below the cutoffs for gestational diabetes, the woman should be rechecked at 24 to 28 weeks with an oral glucose tolerance test. “If any one of those tests is positive for overt diabetes, treat as existing diabetes, not gestational,” Jornsay advised. “It is not going to go away at the end of pregnancy.” At the same time, altering risk factors by lowering blood pressure and low-density lipoproteins have protective effects on both coronary artery disease and glucose control. The current strategy is to screen all women at the initial prenatal visit, she continued. Studies show that 40% of women with gestational diabetes have no overt risk factors. “Another change is that you need only 1 abnormal value to make the diagnosis during pregnancy,” said Jornsay.” You have to have all 3 values be normal to have normal glucose tolerance.” Treatment recommendations are also changing. Although no oral antidiabetic agents have FDA approval for use during pregnancy, some agents have come into common use. Sulfonylureas are not recommended because of high rates of fetal malformation. Metformin should also be avoided during pregnancy. There are conflicting data showing both significant associations with preeclampsia and stillbirths and no significant associations with fetal malformations. Glyburide appears to be safe during pregnancy. Data published in 2000 found minimal transport across the placental barrier, no evidence of drug in cord blood, and no change in neonatal abnormalities. “Many people have been using glyburide for gestational diabetes over the past decade,” Jornsay reported.” Other oral agents, including thiazolidinediones, meglitinides, and alpha-glucosidase inhibitors, have not been studied during pregnancy. PATIENT MANAGEMENT The latest in nonnutritive sweeteners Patients and providers who look for saccharine packets may like the product—or they may not realize the range of nonnutritive, noncaloric sweeteners currently available. “The market for nonnutritive sweeteners has changed dramatically these past few years,” said Beth Hubrich, MS, RD, executive director, Calorie Control Council (CCC), Atlanta, Georgia. “The use of nonnutritive sweeteners continues to grow.” The CCC represents the reduced-calorie and low-fat food and beverage industries. Current nonnutritive sweeteners on the US market include acesulfame K, aspartame, neotomae, saccharin, stevia, and sucralose, Hubrich reported. The FDA has established an allowable daily intake (ADI) for each entity, based on animal safety data. Aspartame, for example, has an ADI of 50 mg/kg per day, whereas sucralose has an ADI of 5 mg/kg per day. Surveys are used to establish an estimated daily intake (EDI). The EDI for aspartame in the general population is 6% of the ADI, Hubrich continued. The EDI is 6.6% for people with diabetes, who typically used more nonnutritive sweeteners than the general population. That is probably good news, Hubrich noted, and not just because it means that people with diabetes are using more nonnutritive sweeteners and less sugar. Use of nonnutritive sweeteners is also associated with a higher intake of fresh fruit, more green leafy vegetables, more whole grains, less meat, and a generally healthier diet. Stevia is the hottest nonnutritive sweetener on the market today, she continued. It can be used to sweeten food and beverages as well as in cooking and baking. Depending on the manufacturer, stevia is sold in packets, shakers, tablets, and granulated form. The next nonnutritive sweetener on the market could be advantame, made by Ajinomoto. It is a combination of aspartame and vanillin and is 20,000 times sweeter than sucrose or 100 times sweeter than aspartame. “This may be the most potent sweetener on the market,” Hubrich said. A Food Additive Petition was filed with FDA in April 2009, but there are no official predictions on when it might be approved. In the meantime, the industry is developing a variety of blended nonnutritive sweeteners such as aspartame-saccharin for use in soft drinks. Other combinations include aspartame-acesulfame K and sucralose-acesulfame K. The goal, Hubrich explained, is improved taste profile. “Taste is always king. If it doesn’t taste good, patients aren’t interested.” DISCLAIMER: |
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