UNC co-leads large clinical trial on new combo therapy for type 2 diabetes

New insulin degludec has comparable cardiovascular safety rates to insulin glargine U100 but with less risk of triggering low blood sugar.

UNC co-leads large clinical trial on new combo therapy for type 2 diabetes click to enlarge John Buse, MD, PhD

June 12, 2017

CHAPEL HILL, NC – The UNC Diabetes Care Center was one of the sites involved in a large clinical trial to determine that a new, ultra-long acting insulin product – insulin degludec – has comparable cardiovascular safety to insulin glargine U100 and is also associated with significant reductions in severe hypoglycemia, or low blood sugar. Investigators, including John Buse, MD, PhD, director of the UNC Diabetes Care Center, presented their findings today during a symposium titled “Cardiovascular Safety of Insulin Degludec vs. Insulin Glargine in Patients with Type 2 Diabetes at High Risk of Cardiovascular Events (DEVOTE) Trial Results,” at the American Diabetes Association’s 77th Scientific Sessions at the San Diego Convention Center.

The Phase 3, multi-center, international, randomized, double-blind DEVOTE study was designed to evaluate the relative cardiovascular safety of insulin degludec (IDeg) compared to insulin glargine (IGlar) U100 when added to a standard of care regimen for people with type 2 diabetes. IDeg is a new generation, once-daily, injectable basal insulin that provides duration of action of at least 42 hours. IGlar is the most commonly prescribed insulin product for people with type 2 diabetes, and its cardiovascular safety was established through the ORIGIN trial published in 2012.

The DEVOTE trial evaluated 7,637 people with type 2 diabetes who were at high risk of major adverse cardiovascular events (MACE), for a period of approximately two years. The study enrolled patients between October 2013 and November 2014 at 436 sites in 20 countries. Of the study participants, 6,506 had prior cardiovascular disease or chronic kidney disease, and the remainder had multiple cardiovascular risk factors. All of the patients were randomized to receive either injectable daily IDeg or IGlar, in addition to the other medications the patients were already taking. However, neither the patient nor the provider knew which insulin formulation they were receiving or giving. This allowed for a robust exploration of safety and efficacy and is unique for insulin comparative studies. 

The study confirmed the cardiovascular safety of IDeg compared to IGlar U100 by demonstrating non-inferiority of MACE, such as first occurrence of cardiovascular death, non-fatal myocardial infarction or non-fatal stroke, occurring with a hazard ratio of 0.91 in favor of IDeg relative to IGlar, with no statistically significant difference between the two treatments.

The findings of the DEVOTE trial also demonstrated the hypoglycemic benefit of IDeg. Severe hypoglycemia is the most serious treatment risk related to insulin therapy, and prior trials have suggested that IDeg is associated with a lower risk of hypoglycemia than IGlar U100, likely related to IDeg’s longer and more consistent insulin action over time.

IDeg resulted in 27 percent fewer patients experiencing an episode of severe hypoglycemia (hypoglycemia requiring the assistance of another person) and a 40 percent overall reduction of total episodes of severe hypoglycemia. Patients in the IDeg-treated group also experienced a 53 percent relative reduction in the rate of nocturnal severe hypoglycemia, which is a common and serious side effect of insulin therapy. All severe hypoglycemic events of the study participants during the trial period were evaluated and confirmed by a group of external experts, and the differences were all statistically significant.

“These results will provide reassurance, both for people with type 2 diabetes and for their health care providers, that this new insulin product has comparable cardiovascular safety to IGlar,” said Buse, MD, director of the NC Translational and Clinical Sciences Institute, and executive associate dean for clinical research at the UNC School of Medicine. “It’s exciting that with IDeg, patients can achieve positive glycemic control along with a major reduction in the risk of severe hypoglycemia, particularly nocturnal severe hypoglycemia.”

John Buse, MD, PhD, is the Verne S. Caviness Distinguished Professor of Medicine and division chief of endocrinology in the department of medicine.

Media contact: Mark Derewicz, 984-974-1915, mark.derewicz@unchealth.unc.edu

About the American Diabetes Association

More than 29 million Americans have diabetes, and every 23 seconds another person is diagnosed with diabetes. The American Diabetes Association (Association) is the global authority on diabetes and since 1940 has been committed to its mission to prevent and cure diabetes and to improve the lives of all people affected by diabetes. To tackle this global public health crisis, the Association drives discovery in research to treat, manage and prevent all types of diabetes, as well as to search for cures; raises voice to the urgency of the diabetes epidemic; and provides support and advocacy for people living with diabetes, those at risk of developing diabetes and the health care professionals who serve them. For more information, please call the American Diabetes Association at 1-800-DIABETES (1-800-342-2383) or visit diabetes.org. Information from both of these sources is available in English and Spanish. Find us on Facebook (American Diabetes Association), Twitter (@AmDiabetesAssn) and Instagram (@AmDiabetesAssn). 

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