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Original Investigation
July 4, 2017

Effect of Insulin Degludec vs Insulin Glargine U100 on Hypoglycemia in Patients With Type 1 DiabetesThe SWITCH 1 Randomized Clinical Trial

Author Affiliations
  • 1Mountain Diabetes and Endocrine Center, Asheville, North Carolina
  • 2AMCR Institute, Escondido, California
  • 3Albany Medical College, Albany, New York
  • 4Medical University of Silesia, Zabrze, Poland
  • 5Scripps Whittier Diabetes Institute, San Diego, California
  • 6Medical & Science, Novo Nordisk A/S, Søborg, Denmark
  • 7Biostatistics Insulin & Diabetes Outcomes, Novo Nordisk A/S, Søborg, Denmark
  • 8Physicians East PA, Greenville, North Carolina
  • 9School of Osteopathic Medicine, Campbell University, Lillington, North Carolina
JAMA. 2017;318(1):33-44. doi:10.1001/jama.2017.7115
Key Points

Question  Is the rate of hypoglycemia noninferior or lower with insulin degludec vs insulin glargine U100 in insulin-treated patients with type 1 diabetes?

Findings  In this randomized crossover trial of 501 patients, insulin degludec compared with insulin glargine U100 resulted in a significantly lower rate of overall symptomatic hypoglycemic episodes over a 16-week maintenance period (2201 vs 2463 episodes per 100 patient-years of exposure).

Meaning  Patients with type 1 diabetes treated with insulin degludec, compared with insulin glargine U100, had a reduced risk of overall symptomatic hypoglycemia.

Abstract

Importance  Hypoglycemia, common in patients with type 1 diabetes, is a major barrier to achieving good glycemic control. Severe hypoglycemia can lead to coma or death.

Objective  To determine whether insulin degludec is noninferior or superior to insulin glargine U100 in reducing the rate of symptomatic hypoglycemic episodes.

Design, Setting, and Participants  Double-blind, randomized, crossover noninferiority trial involving 501 adults with at least 1 hypoglycemia risk factor treated at 84 US and 6 Polish centers (January 2014-January 12, 2016) for two 32-week treatment periods, each with a 16-week titration and a 16-week maintenance period.

Interventions  Patients were randomized 1:1 to receive once-daily insulin degludec followed by insulin glargine U100 (n = 249) or to receive insulin glargine U100 followed by insulin degludec (n = 252) and randomized 1:1 to morning or evening dosing within each treatment sequence.

Main Outcomes and Measures  The primary end point was the rate of overall severe or blood glucose-confirmed (<56 mg/dL) symptomatic hypoglycemic episodes during the maintenance period. Secondary end points included the rate of nocturnal symptomatic hypoglycemic episodes and proportion of patients with severe hypoglycemia during the maintenance period. The noninferiority criterion for the primary end point and for the secondary end point of nocturnal hypoglycemia was defined as an upper limit of the 2-sided 95% CI for a rate ratio of 1.10 or lower; if noninferiority was established, 2-sided statistical testing for superiority was conducted.

Results  Of the 501 patients randomized (mean age, 45.9 years; 53.7% men), 395 (78.8%) completed the trial. During the maintenance period, the rates of overall symptomatic hypoglycemia were 2200.9 episodes per 100 person-years’ exposure (PYE) in the insulin degludec group vs 2462.7 episodes per 100 PYE in the insulin glargine U100 group for a rate ratio (RR) of 0.89 (95% CI, 0.85-0.94; P < .001 for noninferiority; P < .001 for superiority; rate difference, −130.31 episodes per 100 PYE; 95% CI, −193.5 to −67.16). The rates of nocturnal symptomatic hypoglycemia were 277.1 per 100 PYE in the insulin degludec group vs 428.6 episodes per 100 PYE in the insulin glargine U100 group, for an RR of 0.64 (95% CI, 0.56-0.73; P < .001 for noninferiority; P < .001 for superiority; rate difference, −61.94 episodes per 100 PYE; 95% CI, −83.85 to −40.03). A lower proportion of patients in the insulin degludec than in the insulin glargine U100 group experienced severe hypoglycemia during the maintenance period (10.3%, 95% CI, 7.3%-13.3% vs 17.1%, 95% CI, 13.4%-20.8%, respectively; McNemar P = .002; risk difference, −6.8%; 95% CI, −10.8% to −2.7%).

Conclusions and Relevance  Among patients with type 1 diabetes and at least 1 risk factor for hypoglycemia, 32 weeks’ treatment with insulin degludec vs insulin glargine U100 resulted in a reduced rate of overall symptomatic hypoglycemic episodes.

Trial Registration  clinicaltrials.gov Identifier: NCT02034513

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