Insulin degludec decreased both the rate and the severity of hypoglycemic episodes in adults with type 1 and type 2 diabetes, compared with insulin glargine, in two head-to-head trials sponsored by the maker of insulin degludec and reported online July 3 in JAMA.
The two trials had identical randomized double-blind crossover designs. The first involved 501 adults with type 1 diabetes treated at 84 sites in the United States and 6 sites in Poland, and the second involved 721 adults with type 2 diabetes treated at 152 sites in the United States. All the study participants were at risk for hypoglycemia by virtue of experiencing one or more severe hypoglycemic episodes within the preceding year, having moderate chronic renal failure, having a 15-year or longer duration of diabetes, being unaware of their hypoglycemic symptoms, or experiencing severe hypoglycemia within the 3 months preceding baseline.
In both trials, patients were randomized to one type of once-daily insulin for 32 weeks (a 16-week titration period followed by a 16-week maintenance period) and then crossed over to the other type of insulin for 32 weeks. The primary end point in both studies was the rate of overall severe hypoglycemia during the maintenance period. This was defined as either an episode requiring the assistance of another person to administer aid or an episode in which blood glucose measured less than 56 mg/dL.
In the first trial, rates of hypoglycemia were significantly lower with insulin degludec (2,201 episodes per 100 person-years of exposure) than with insulin glargine (2,463 episodes per 100 PYE), demonstrating not just the noninferiority but also the superiority of insulin degludec. In addition, a significantly lower proportion of patients had hypoglycemia with insulin degludec (32.8%) than with insulin glargine (43.1%), said Wendy Lane, MD, of Mountain Diabetes and Endocrine Center, Asheville NC, and her associates.
Regarding the severity of hypoglycemia, the rate of severe episodes was significantly lower with insulin degludec (69 episodes per 100 PYE) than with insulin glargine (92 episodes per 100 PYE). In addition, the proportion of patients who experienced a severe hypoglycemic episode was significantly lower with insulin degludec (10.3%) than with insulin glargine (17.1%).
Both types of insulin reduced hemoglobin A1c levels to 7% or below. Rates of adverse events and serious adverse events were similar between the two study groups, and there were no differences between them in weight change, blood pressure, pulse rate, or laboratory findings, the investigators said ( JAMA.2017;318:33-44 ).
In the second trial, rates of hypoglycemia again were significantly lower with insulin degludec than with insulin glargine (186 vs. 265 episodes per 100 PYE). In addition, the proportion of patients who experienced a severe hypoglycemic episode was 1.6% vs. 2.4%, respectively, said Carol Wysham, MD, of Rockwood Clinic University of Washington, Spokane, and her associates.
As in the first trial, both types of insulin reduced HbA1c levels to the same degree, and rates of adverse events and of serious adverse events were comparable, Dr. Wysham and her associates said ( JAMA. 2017;318:45-56 ).
The dropout rates were similar and higher than expected in both trials, at approximately 20%. Dr. Lane and her associates noted that this may have resulted from “the demanding nature” of the studies, including their 64-week duration; demand for close monitoring of blood glucose; and the requirement of using vials and syringes to maintain treatment blinding, instead of more convenient injector devices.
Both trials were funded by Novo Nordisk, maker of insulin degludec. Dr. Lane reported ties to Novo Nordisk, Insulet Corporation, and Eli Lilly, and her associates reported ties to numerous industry sources. Dr. Wysham reported ties to Novo Nordisk, AstraZeneca, Boehringer Ingelheim, Eli Lilly, Janssen, and Sanofi, and her associates reported ties to numerous industry sources.