Effect of Insulin Degludec vs Insulin Glargine U100 on Hypoglycemia in Patients With Type 2 Diabetes
Authors: Carol Wysham, Anuj Bhargava, Louis Chaykin, Raymond de la Rosa, Yehuda Handelsman, Lone N. Troelsen, Kajsa Kvist, Paul Norwood
Journal: JAMA (2017)

<h3>Importance</h3> Hypoglycemia, a serious risk for insulin-treated patients with type 2 diabetes, negatively affects glycemic control. <h3>Objective</h3> To test whether treatment with basal insulin degludec is associated with a lower rate of hypoglycemia compared with insulin glargine U100 in patients with type 2 diabetes. <h3>Design, Setting, and Participants</h3> Randomized, double-blind, treat-to-target crossover trial including two 32-week treatment periods, each with a 16-week titration period and a 16-week maintenance period. The trial was conducted at 152 US centers between January 2014 and December 2015 in 721 adults with type 2 diabetes and at least 1 hypoglycemia risk factor who were previously treated with basal insulin with or without oral antidiabetic drugs. <h3>Interventions</h3> Patients were randomized 1:1 to receive once-daily insulin degludec followed by insulin glargine U100 (n = 361) or to receive insulin glargine U100 followed by insulin degludec (n = 360) and randomized 1:1 to morning or evening dosing within each treatment sequence. <h3>Main Outcomes and Measures</h3> The primary end point was the rate of overall symptomatic hypoglycemic episodes (severe or blood glucose confirmed [&lt;56 mg/dL]) during the maintenance period. Secondary end points were the rate of nocturnal symptomatic hypoglycemic episodes (severe or blood glucose confirmed, occurring between 12:01amand 5:59am) and the proportion of patients with severe hypoglycemia during the maintenance period. <h3>Results</h3> Of the 721 patients randomized (mean [SD] age, 61.4 [10.5] years; 53.1% male), 580 (80.4%) completed the trial. During the maintenance period, the rates of overall symptomatic hypoglycemia for insulin degludec vs insulin glargine U100 were 185.6 vs 265.4 episodes per 100 patient-years of exposure (PYE) (rate ratio = 0.70 [95% CI, 0.61-0.80];<i>P</i> &lt; .001; difference, −23.66 episodes/100 PYE [95% CI, −33.98 to −13.33]), and the proportions of patients with hypoglycemic episodes were 22.5% vs 31.6% (difference, −9.1% [95% CI, −13.1% to −5.0%]). The rates of nocturnal symptomatic hypoglycemia with insulin degludec vs insulin glargine U100 were 55.2 vs 93.6 episodes/100 PYE (rate ratio = 0.58 [95% CI, 0.46-0.74];<i>P</i> &lt; .001; difference, −7.41 episodes/100 PYE [95% CI, −11.98 to −2.85]), and the proportions of patients with hypoglycemic episodes were 9.7% vs 14.7% (difference, −5.1% [95% CI, −8.1% to −2.0%]). The proportions of patients experiencing severe hypoglycemia during the maintenance period were 1.6% (95% CI, 0.6%-2.7%) for insulin degludec vs 2.4% (95% CI, 1.1%-3.7%) for insulin glargine U100 (McNemar<i>P</i> = .35; risk difference, −0.8% [95% CI, −2.2% to 0.5%]). Statistically significant reductions in overall and nocturnal symptomatic hypoglycemia for insulin degludec vs insulin glargine U100 were also seen for the full treatment period. <h3>Conclusions and Relevance</h3> Among patients with type 2 diabetes treated with insulin and with at least 1 hypoglycemia risk factor, 32 weeks' treatment with insulin degludec vs insulin glargine U100 resulted in a reduced rate of overall symptomatic hypoglycemia. <h3>Trial Registration</h3> clinicaltrials.gov Identifier:NCT02030600