American Diabetes Association 74th Scientific Sessions

American Diabetes Association 74th Scientific Sessions

San Francisco, CA

June 13-17, 2014

The 74th Scientific Sessions of the American Diabetes Association (ADA) brought together more than 17,300 attendees from more than 121 countries. This year’s program included 96 symposia, 50 oral abstract sessions, 10 interest group discussions, 18 meet-the-expert sessions, and 10 special lectures and addresses. Cardiology Review is covering 6 of the top sessions.

First ADA Guidance Issued Specifically for Type 1 Diabetes Melllitus

The ADA issued a new position statement that provides the first-ever guidance directed to the management of type 1 diabetes mellitus (T1DM) in all age groups, including a new glycated hemoglobin (A1C) target for children. “Type 1 Diabetes Through the Life Span” was simultaneously published online in Diabetes Care. The new guidance document grew out of the recognition that there was little information specific to T1DM in adults and that evidence from research on type 2 diabetes mellitus (T2DM) was being inappropriately extrapolated to treatment of T1DM. Examples of this include universal recommendations for statin use and LDL-cholesterol targets derived from populations with T2DM. In addition, limitations on insurance reimbursement for glucometer test strips were impeding adequate testing by patients with T1DM because so many insurers were basing coverage on the needs of people with T2DM.

The guide recommends a new pediatric glycemic control target A1C of less than 7.5% across all age groups, rather than calling for different targets by age as before. The previous targets are now considered out of date because they were based on experience with severe hypoglycemia in years past, when currently available technologies such as continuous glucose monitoring, insulin pumps, and insulin analogues were not available and tight glucose control presented a greater risk of hypoglycemia. In addition, new research shows that rates of hypoglycemia aren’t higher in the youngest patients, or in those with lower A1C levels.

The adult A1C target of 7% for T1DM remains the same, with individualized lower or higher targets based on patient need.

Lori M. B. Laffel, MD, chief of the pediatric, adolescent, and young adult section at the Joslin Diabetes Center, and associate professor of pediatrics at Harvard Medical School, said that she was pleased to be able to offer a single set of guidelines that will cross the entire lifespan of patients with T1DM so that as patients pass into adulthood theywill be treated properly.

Guideline coauthor Anne L. Peters, MD, professor of medicine at the Keck School of Medicine, University of Southern California, Los Angeles, noted that there are an estimated 3 million people with T1DM in the United States, of whom only about 160,000 are children. She pointed out that it is not a pediatric disease, and that we must remember that the vast majority of people with T1DM are adults.

Study Says Statins for Primary Prevention Not Cost-Effective

Recent guidelines from the American College of Cardiology (ACC)/American Heart Association (AHA) newly endorsed statins for primary prevention of cardiovascular disease (CVD), making an estimated 18 to 19 million Americans eligible for statin treatment for this indication. However, a new study from Centers for Disease Control and Prevention researchers suggests that statin use is not cost-effective in a significant proportion of the target population recommended in the new guideline, including people with a cardiovascular disease risk of 7.5% to 10%, regardless of their status with respect to diabetes.

The study investigated the cost-effectiveness of statin therapy with the new guidelines by investigating 2 of the 4 patient groups the guidelines make eligible for statins: 1) individuals with diabetes between the ages of 40 and 75 years with low-density lipoprotein cholesterol (LDL-C) levels between 70 and 189 mg/dL and no evidence of atherosclerotic CVD, and 2) people with no evidence of atherosclerotic CVD or diabetes but with LDL-C levels between 70 and 189 mg/dL and a 10-year risk for atherosclerotic CVD >7.5%.

The researchers developed a model that took a nationally representative sample of Americans from the 2005 to 2010 National Health and Nutrition Examination Survey (NHANES) and estimated the lifetime risk for atherosclerotic CVD and diabetes, as well as cost per quality-adjusted life-year (QALY) gained by following the new AHA/ACC guidelines.

Using a $50,000 per QALY benchmark, the investigators found that intensive statin use was cost-effective in diabetic patients if their CVD risk was greater than 10%, while moderate statin use was not cost-effective if CVD risk was between 7.5% and 10%. In nondiabetic adults, moderate statin use was cost-effective if their CVD risk was >10%, but was not cost-effective, particularly in those with prediabetes.

Xiaohui Zhuo, PhD, said the new guidelines are a drastic change from the previous ATP3 guidelines and are quite controversial. “Health benefits of statin use among a low-risk population without diabetes still carry a lot of uncertainty, especially because these patients have poor medication adherence, and statin use is linked with an increased risk of type 2 diabetes mellitus and myopathies.”

"Bionic Pancreas" Achieves Milestone 5-Day Successful Real World Use

Two studies of 20 adults and 32 adolescents with T1DM reported that a closed-loop “artificial pancreas” was found to work for 5 consecutive days in an outpatient setting. In both studies, patients received 5 days of bionic pancreas treatment and 5 days of usual pump therapy in random order.

The bionic pancreas, being developed in a collaboration between Massachusetts General Hospital/Harvard Medical School and a team at Boston University, is wearable, automated, and incorporates glucagon in addition to insulin. The use of glucagon in addition to insulin is a big difference between this closed-loop system and others being developed. The bionic pancreas device consists of an iPhone, which runs a control algorithm, and a Dexcom continuous glucose monitor (CGM), connected by a hardware interface that displays CGM readings and insulin and glucagon doses. Both insulin and glucagon are delivered subcutaneously by t:slim infusion pumps (Tandem Diabetes Care).

In the study of adults, subjects lived at home during the usual-care period and carried out their normal activities while wearing their own insulin pump and their own CGM, if desired. In the bionic pancreas period, they stayed in a hotel and were allowed to move freely within a 3-mile area of Boston, with a staff member. Mean plasma glucose level during the bionic pancreas period was 138 mg/dL (range, 116-166 mg/dL); time spent with plasma glucose levels <70 mg/dL was 4.8%, and <60 mg/dL was 2.3%. Mean glucose levels on CGM were similar to plasma glucose readings.

Mean glucose levels on CGM (days 2 through 5) were 133 mg/dL with the bionic pancreas compared with 159 mg/dL with usual care (P <.001). Percentage of time with glucose levels <70 mg/dL was 4.1% versus 7.3% (P <.001) and <60 mg/dL was 1.5% versus 3.7% (P = .02).

Differences between bionic pancreas and control periods were more pronounced at night. There were no severe hypoglycemic events. Nausea with and without vomiting each occurred once within 2 h after a glucagon dose; 3 insulin infusion sets and 1 glucagon infusion set were removed during the bionic pancreas period due to pain or inflammation.

The study in adolescents (12 to 21 years old) took place at a diabetes summer camp, where the children were closely monitored. Mean plasma glucose was also lower during the bionic pancreas period than during the control period (138 mg/dL vs 157 mg/dL; P = .04), but the percentage of time spent in the hypoglycemic range was similar during the 2 periods (6.1% vs 7.6%; P = .23).

Interventions for hypoglycemia over the 5 days were needed in 1 of every 1.6 days during the bionic pancreas period compared with 1 per 0.8 days during the control period. Side effects from glucagon were similar to those in adults.

Replacements for Lantus Show Promise in Studies:

Two experimental insulin therapies were shown to be promising as replacements for the basal insulin Lantus, according to data from several large clinical trials reported at the ADA meeting.

Toujeo (Sanofi’s experimental insulin glargine product) is expected to succeed Lantus when the latter drug loses patent product early in 2015. Eli Lilly has a version of insulin glargine that it is also readying for the market.

Late-stage studies of Toujeo showed that patients with T2DM were 31% less likely to have potentially dangerous declines in blood sugar in the night than those taking Lantus. Toujeo has the same active ingredient as Lantus but in a 3-fold higher concentration than Lantus, and its activity level does not increase overnight, according to data from a combined review of 2 phase 2 Sanofi-sponsored trials. A late-stage study of the drug in patients with T1DM showed that rates of hypoglycemia and overall blood glucose control were similar for Toujeo and Lantus.

Lilly’s insulin glargine was shown to be as effective and safe as Lantus for patients with T1DM and T2DM, with a similar rate of hypoglycemia, according to 6 studies sponsored by Lilly and Boehringer Ingelheim.

Experimental Combo of Insulin Degludec and Victoza Effective

Novo Nordisk’s combination of its long-acting insulin degludec and its T2DM medication liraglutide (Victoza) was shown to be able to achieve superior blood glucose reduction after 1 year compared with each medication separately. The combination therapy also appeared to help more patients reach recommended blood glucose levels, and to experience reduced side effects, compared with taking each medication alone.

In the 1-year late-stage trial of 1663 patients with T2DM whose blood glucose was not well controlled by metformin, patients taking the combination drug IDegLira had an average 1.8% reduction in A1C level, compared with an average A1C decline of 1.4% for the insulin and 1.2% for liraglutide.

Average A1C level after 1 year was 6.4% for IDegLira, 6.9% for insulin degludec, and 71% for liraglutide. A total of 78% of IDegLira patients achieved A1C levels <7% versus 63% for degludec and 57% for liraglutide.

Investigators reported that patients taking IDegLira had a mean weight reduction of 0.4 kg. That compares with an average weight gain of 2.3 kg for insulin degludec and a loss of 3 kg for liraglutide. IDegLira also led to a 37% lower rate of hypoglycemia than degludec. Furthermore, nausea and other gastrointestinal side effects associated with liraglutide were reduced dramatically by the slow titration of the combination drug, investigators said.

Diabetes Can Be Delayed by Lifestyle Changes, Metformin

New findings from the ongoing US Diabetes Prevention Program (DPP) suggest that overweight or obese people at high risk for T2DM can reduce or delay the development of T2DM for as much as 15 years when randomized to intensive lifestyle changes or metformin (850 mg, twice daily).

Investigator Marinella G. Temposa, PhD, of George Washington University, said that although half of the approximately 3000 study participants did develop T2DM during the 16-year time period, the results showed that diabetes is not inevitable in people at high risk. The study found that both interventions were effective in delaying the onset of diabetes, and 85% of the original cohort chose to continue in the extension program (DPP Outcomes Study). The researchers pointed out that 45% of participants were from minority ethnic backgrounds.

The study included a placebo arm as well. The researchers reported a 27% reduction in prevalence of diabetes among the original intensive-lifestyle group compared with the original placebo group, and an 18% reduction in the original metformin group compared with placebo. There has been a 1.1-year shorter duration of diabetes over the 16 years studied, and a 3% to 4% weight loss and 0.1% lower A1C.

Researchers said that while it is too soon to conclude whether a significant benefit can be derived from either metformin or intensive lifestyle changes in terms of preventing cardiovascular disease (CVD) or diabetic retinopathy, nephropathy, and neuropathy, there are encouraging signs, with one investigator suggesting that lifestyle intervention appeared to have the strongest effect on CVD risk factors.

Questions remain to be answered, among them: (1) When is the best time to introduce prophylaxis for long-term complications? and (2) what is the effect of long-term metformin during the phase before diabetes on CVD and cancer?