Practice Update: Diabetes

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New, Ultra-Long-Acting Insulin Degludec Demonstrates
Cardiovascular Safety and Reduces Risk of Severe Hypoglycemia
A new, ultra-long-acting insulin product, insulin degludec, has been found to confer comparable cardiovascular safety
to insulin glargine U100 and is also associated with significant reductions in severe hypoglycemia. This outcome of
the phase 3, multicenter, international, randomized, double-blind Cardiovascular Safety of Insulin Degludec vs Insulin
Glargine in Patients with Type 2 Diabetes at High Risk of Cardiovascular Events (DEVOTE) trial was reported at the
American Diabetes Association’s 77th Scientific Sessions, from June 9–13.
Steven Marso, MD, of HCA Midwest
Health, Kansas City, Missouri,
explained that the DEVOTE trial
evaluated the relative cardiovascular safety
of insulin degludec vs insulin glargine U100
when added to a standard-of-care regimen
for patients with type 2 diabetes.
Insulin degludec is a new-generation, once-
daily, injectable basal insulin that provides
duration of action of at least 42 h. Insulin
glargine is the most commonly prescribed
insulin product for type 2 diabetes. Its
cardiovascular safety was established in
the 2012 Outcome Reduction with an Initial
Glargine Intervention (ORIGIN) trial.
The DEVOTE trial evaluated 7637 patients
with type 2 diabetes who were at high risk
of major adverse cardiovascular events,
for a period of approximately 2 years. The
study enrolled patients between 2013 and
2014 at 436 sites in 20 countries. Of study
participants, 6506 had suffered from prior
cardiovascular disease or chronic kidney
disease, and the remainder had multiple
cardiovascular risk factors.
All patients were randomized to either
injectable daily insulin degludec or insulin
glargine, in addition to other medications
the patients had been taking. Neither
patient nor provider, however, knew which
insulin formulation the patient was receiving/
administering. This blinding allowed for a
robust exploration of safety and efficacy and
is unique for comparative studies of insulin.
Results of the study confirmed the
cardiovascular safety of insulin degludec
vs insulin glargine U100 by demonstrating
noninferiority of major adverse cardiac
events, such as first occurrence of
cardiovascular death, nonfatal myocardial
infarction or nonfatal stroke (hazard
ratio 0.91 in favor of insulin degludec vs
insulin glargine, no statistically significant
difference between the two treatments).
Findings of DEVOTE also demonstrated the
hypoglycemic benefit of insulin degludec.
Severe hypoglycemia remains the most
serious treatment risk of insulin therapy,
and trials have suggested that insulin
degludec is associated with a lower risk
of hypoglycemia than insulin glargine U100.
Severe hypoglycemia is the most serious
acute complication of insulin treatment
and can be lead to seizures, coma, and
even death. Insulin degludec resulted
in 27% fewer episodes of severe
hypoglycemia and 40% overall reduction
of total episodes of severe hypoglycemia.
Patients in the insulin degludec group also
experienced a 53% reduction in the rate of
nocturnal severe hypoglycemia. All severe
hypoglycemic events were evaluated
and confirmed by external experts, and
differences were all statistically significant.
Dr Marso concluded, “Findings of the
DEVOTE study are in line with previous
clinical trials comparing insulin degludec vs
insulin glargine U100, so we are pleased to
provide conclusive evidence of the safety
of insulin degludec for patients with type
2 diabetes at high risk of cardiovascular
complications.”
Coinvestigator John Buse, MD, PhD, of
the University of North Carolina School of
Medicine, Chapel Hill, said, “These results
provide reassurance that this new insulin
product confers comparable cardiovascular
safety to insulin glargine. It is exciting that
with insulin degludec, patients can achieve
positive glycemic control along with a major
reduction in the risk of severe hypoglycemia,
particularly nocturnal severe hypoglycemia.”
PracticeUpdate Editorial team.
These results provide
reassurance that this
new insulin product
confers comparable
cardiovascular safety
to insulin glargine.
ADA 2017 13
VOL. 1 • NO. 2 • 2017