Effect of insulin degludec vs insulin glargine U100 on hypoglycemia in patients with type 2 diabetes the SWITCH 2 randomized clinical trial

Abstract

IMPORTANCE Hypoglycemia, a serious risk for insulin-Treated patients with type 2 diabetes, negatively affects glycemic control. OBJECTIVE 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. DESIGN, SETTING, AND PARTICIPANTS 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. INTERVENTIONS Patientswere randomized 1:1 to receive once-daily insulin degludec followed by insulin glargineU100(n = 361) or to receive insulin glargineU100followed by insulin degludec (n = 360) and randomized 1:1 to morning or evening dosing within each treatment sequence. MAIN OUTCOMES AND MEASURES The primary end pointwas the rate of overall symptomatic hypoglycemic episodes (severe or blood glucose confirmed [<56mg/dL]) duringthe maintenance period. Secondary end pointswere 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. RESULTS 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]; P