Patients with type 2 diabetes assigned insulin degludec saw significantly lower rates of nocturnal hypoglycemia compared with patients assigned insulin glargine, according to results of a meta-analysis published in Diabetic Medicine.
In a post-hoc, meta-analysis of six randomized controlled phase 3a trials spanning 26 or 52 weeks, researchers also found that patients with type 1 diabetes assigned insulin degludec saw similar or lower rates of nocturnal hypoglycemia vs. those assigned insulin glargine, and that the lower rates persisted across different definitions of hypoglycemia.
Simon Heller, MD, professor of clinical diabetes at the University of Sheffield, U.K., and colleagues analyzed data from three trials including insulin-naive patients with type 2 diabetes: one trial including patients with type 2 diabetes using a basal-bolus insulin regimen and two trials including patients with type 1 diabetes. Researchers analyzed rates of nocturnal hypoglycemia for the entire core trial period, the “maintenance period” only and the extension period (four trials continued for a longer duration). For all trials, the nocturnal period was defined as 00:01 to 5:59; researchers also performed sensitivity analyses for confirmed hypoglycemic episodes accompanied by symptoms, and symptomatic events with a plasma glucose less than 3.9 mmol/L. Researchers added 2 hours to either end of the nocturnal period in separate analyses to test the robustness of results.
Participants with type 2 diabetes who were insulin-naive experienced consistently lower rates of nocturnal hypoglycemia with insulin degludec vs. insulin glargine, with the difference ranging between 5 and 44 episodes per 100 patients-years of exposure, depending on the definition of hypoglycemia and the nocturnal period.
However, when researchers added 2 morning hours to the nocturnal definition, the risk was only lower during the maintenance period. Participants experienced a two- to threefold increase in the number of hypoglycemic episodes during the extended timescale of 0:01 to 7:59, according to researchers.
“This might be the result of a later waking time, or diabetes therapies taken at breakfast,” the researchers wrote. “One possible contributing factor may have been that pre-breakfast plasma glucose testing was prescribed by the study protocols for insulin titration decisions, and that asymptomatic hypoglycemia, which would have gone unrecorded, was therefore detected.”
Participants with type 2 diabetes on basal-bolus therapy also experienced lower rates of hypoglycemia with insulin degludec vs. insulin glargine across all hypoglycemia definitions, timescales and trial periods, with one exception during the maintenance period.
Participants with type 1 diabetes assigned either insulin degludec or insulin glargine experienced similar rates of hypoglycemia during the core trial period; however, risk was significantly lower for those assigned insulin degludec during the maintenance period when using the 00:01 to 5:59 time scale and original definition for reporting hypoglycemia. The trial extension group with type 1 diabetes also saw significantly reduced risk for hypoglycemia across all definitions and between the hours of 21:59 and 5:59.
Researchers also found that participants in the extension period had a more favorable risk ratio with insulin degludec vs. insulin glargine when compared with participants in the core trial period.
“This suggests that the risk reduction with insulin degludec is a sustained effect and may improve as patients learn to optimize the use of this new insulin,” the researchers wrote. – by Regina Schaffer
Novo Nordisk supported this study; two of the study researchers are employees of Novo Nordisk and hold stock in the company. Please see the full study for the other researchers’ relevant financial disclosures.