Hypoglycemia may increase the risk for
acute cardiovascular events in patients with diabetes and also the
risk for inpatient mortality in hospitalized patients treated with
insulin, irrespective of whether or not they have diabetes,
researchers have reported.

In two separate sessions presented at the American Diabetes 70th
scientific sessions in Orlando, Florida, USA, researchers described
the problems associated with low blood glucose in patients with
diabetes and those treated with insulin.

However, in both cases the researchers warned that it is too
early for a causative relationship between hypoglycemia and these
events to be concluded, and they call for further research to be
done.

In the first presentation, Christopher Connor, from Novo Nordisk
in Seattle, Washington, USA, reported his team’s retrospective
examination of the association between hypoglycemia and acute
cardiovascular events, including acute myocardial infarction,
coronary artery bypass, grafting, revascularization, percutaneous
transluminal coronary angioplasty, and new unstable angina, in
patients with Type 2 diabetes.

The data on 860,845 diabetic patients aged at least 18 years
were obtained from healthcare claims for individuals with
employer-sponsored primary or Medicare supplemental insurance.

Between 2006/7 and 2007/8, 27,065 of the patients suffered at
least one ICD-9-CM coded outpatient hypoglycemic event.

Logistic regression adjusting for confounding factors, such as
age, gender, insurance type, region, comorbidity, cardiovascular
risk factors, prior acute cardiovascular events, and diabetes
complications, showed that patients with hypoglycemic events were
79% more likely to suffer an acute cardiovascular event than were
patients without hypoglycemic events.

Connor noted that the findings should be considered in context,
however, saying that their “analyses neither suggest, nor address,
any role of glycemic control in the relationship between
hypoglycemic episodes and the risk for acute cardiovascular
events.”

He added: “Good glycemic control is of critical importance, with
current expert consensus that there is no need for major changes in
glycemic control targets.”

In the second presentation, Kimberly Brodovicz, from Merck
Research Laboratories, told delegates that in their study of
107,312 hospitalized insulin-treated patients, hypoglycemia
occurred in 21,561 patients, (non-severe hypoglycemia [?70
mg/dl] in 14,022 and severe hypoglycemia [?50 mg/dl] in 7539
patients). Among the patients with hypoglycemia, 6.5% died while in
hospital, compared with 3.8% of patients without hypoglycemia. The
rate increased to 8.0% among those with severe hypoglycemia.

Logistic regression analyses accounting for age, gender,
hospital characteristics, and the comorbidities heart failure,
chronic kidney disease, bacteremia, and infection showed the risk
for inpatient mortality was 46% higher for patients with than
without hypoglycemia and 73% higher for those with severe
hypoglycemia.

However, the risks for ischemic events and neurologic
complications were not increased significantly in patients with
hypoglycemia.

Brodovicz noted that a direct causal relationship cannot be
assumed from the findings.

“We don’t know whether hypoglycemia in these analyses is a
marker for sicker patients or whether it is the hypoglycemia itself
that is causing this increased risk in inpatient mortality,” she
pointed out.

MedWire (www.medwire-news.md) is an independent clinical news
service provided by Current Medicine Group, a trading division of
Springer Healthcare Limited. © Springer Healthcare Ltd;
2010

Meeting website

Exenatide provided once a week as an
extended-release injectable suspension appears to be as well
tolerated as the currently available twice-daily exenatide, and may
even provide better tolerability due to a lower incidence of
gastrointestinal (GI) events and low rate of nausea, study findings
show.

The findings have emerged from a pooled analysis of the safety
data from the completed DURATION (Diabetes Therapy Utilization:
Researching Changes in A1C, Weight and Other Factors Through
Intervention With Exenatide Once Weekly)-1, 2, and 3 trials,
involving a total of 1095 patients with Type 2 diabetes who were
monitored for a period of 26-30 weeks.

Of these patients, 541 were treated with the once-weekly
exenatide, a glucagon-like peptide (GP)-1 receptor agonist, while
554 were treated with sitagliptin, pioglitazone, or insulin
glargine.

Selected analyses comparing patients taking once-weekly
exenatide and 145 patients taking twice-daily exenatide were also
conducted.

The patients had a mean age of 52-58 years, a baseline glycated
hemoglobin (HbA1c) level of 8.3-8.5%, and had suffered from
diabetes for 6-8 years.

Dana Lee, from Amylin Pharmaceuticals in San Diego, California,
USA, told delegates at the American Diabetes 70th scientific
sessions in Orlando, Florida, USA, that the overall incidence of
adverse events in the patients was low and similar for patients
taking once-weekly exenatide and those in the pooled group, at 77%
and 71%, respectively.

Discontinuations due to adverse events were also low, at less
than 1% in both treatment groups, with no significant
difference.

There was one death in each treatment group, but these were
unrelated to treatment.

Common treatment-emergent adverse events (frequency ?5%)
that were seen more often in patients taking once-weekly exenatide
than in those in the pooled comparator group were injection-site
pruritis (7 vs 2%) and gastrointestinal symptoms, including nausea
(20 vs 5%), vomiting (8 vs 2%), diarrhea (13 vs 7%), and
constipation (6 vs 2%).

However, the rate of nausea and vomiting with once-weekly
exenatide was about half that seen with twice-daily exenatide, and
Lee noted that after 3 months of treatment with exenatide once a
week, at which point a steady-state level is reached, only
approximately 1% of patients reported new nausea.

The risk for hypoglycemia was lower for patients taking
once-weekly exenatide, at 16% versus 19% for patients taking
twice-daily exenatide and 22% for the pooled comparator group, and
there were no events of major hypoglycemia.

Composite exposure-adjusted incidence rates (per 100
patient-years) of events potentially associated with specific GP-1
agents or the broader class of incretin agents, including
pancreatitis, renal impairment/dehydration, and adverse events
associated with the gall bladder and thyroid neoplasm, were similar
for once-weekly exenatide-treated patients and the pooled
comparator group.

Lee concluded: “No safety signals of concern were identified for
once-weekly exenatide in this integrated analysis.

“The continuous GLP-1 receptor agonism provided by the exenatide
once weekly demonstrated a safety profile that is similar to the
current exenatide twice a day, which has been in clinical use for
over 5 years.”

MedWire (www.medwire-news.md) is an independent clinical news
service provided by Current Medicine Group, a trading division of
Springer Healthcare Limited. © Springer Healthcare Ltd;
2010

Meeting website

A multicomponent school-based intervention
has demonstrated partial success in reducing adiposity and diabetes
risk in high-risk sixth-grade students.

The US federally funded study, called “HEALTHY,” failed to
decrease the combined prevalence of overweight and obesity but did
reduce obesity rates and fasting insulin when compared with
non-intervention schools.

The study appears in the New England Journal of Medicine
to coincide with presentation of the results at the 70th annual
scientific sessions of the American Diabetes Association (ADA) in
Orlando, Florida. The study was co-funded by the National Institute
for Diabetes and Digestive and Kidney Diseases, part of the
National Institutes of Health, and the ADA.

The goal of the HEALTHY study was to determine whether healthier
food choices, an increase in physical activity, and
health-promoting activities and awareness campaigns would reduce
risk factors for Type 2 diabetes.

Because Type 2 diabetes disproportionately affects ethnic
minorities and low-income individuals, the study was conducted in
schools with a preponderance of children from these groups.

Using a cluster design, 42 schools were randomly assigned to
intervention or no intervention (control). A total of 4603 children
participated; their mean age was 11.3 years, 54.3% were Hispanic,
18% were African American, and 75% were eligible for free or
reduced-price meals.

The intervention lasted from the beginning of sixth grade to the
end of the eighth grade. It had three components: Healthier choices
in the cafeteria, snack bars, class events, and vending machines;
longer, more intense periods of physical activity; and activities
and awareness campaigns that promoted long-term healthy
behaviors.

The study’s primary outcome - the combined prevalence of
overweight and obesity - fell by 4.1% in control schools and by
4.5% in intervention schools, a non-significant difference.

The reduction in overweight and obesity in control schools was
“a welcome but unexpected finding,” remarked Gary Foster (Temple
University, Philadelphia), the study’s lead author. “Future
analyses will try to clarify the reasons for the improvement in
these schools.”

Some other outcomes did differ between intervention and control
schools. For instance, students in intervention schools who were
overweight/obese in the sixth grade were 21% less likely to be
obese at the end of the eighth grade compared with their
counterparts in control schools.

Furthermore, intervention schools had a significantly lower
percentage of students with a waist circumference at or above the
90th percentile at the end of the study (21.3% vs 22.7%).
Additionally, mean insulin levels in the eighth grade were
significantly lower in students in intervention versus control
schools (16.9 vs 17.4 U/ml).

The investigators conclude: “These changes may reduce the risk
of childhood-onset Type 2 diabetes.”

“We will only stop the diabetes epidemic if we continue to test
innovative approaches to help children make healthy lifestyle
choices,” remarked Richard Bergenstal, president of Medicine and
Science at the ADA. “The HEALTHY Study shows us an effective
approach that can be implemented to improve the outcomes of a large
number of youth at very high risk of diabetes.”

MedWire (www.medwire-news.md) is an independent clinical news
service provided by Current Medicine Group, a trading division of
Springer Healthcare Limited. © Springer Healthcare Ltd;
2010

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