Effect of Insulin Degludec vs Insulin Glargine U100 on Hypoglycemia in Patients With Type 2 Diabetes: The SWITCH 2 Randomized Clinical Trial

JAMA. 2017 Jul 4;318(1):45-56. doi: 10.1001/jama.2017.7117.

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: 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.

Main outcomes and measures: The primary end point was the rate of overall symptomatic hypoglycemic episodes (severe or blood glucose confirmed [<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 12:01 am and 5:59 am) 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 < .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]; P < .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 P = .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.

Conclusions and relevance: 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.

Trial registration: clinicaltrials.gov Identifier: NCT02030600.

Publication types

  • Comparative Study
  • Multicenter Study
  • Randomized Controlled Trial

MeSH terms

  • Adult
  • Aged
  • Blood Glucose / analysis
  • Cross-Over Studies
  • Diabetes Mellitus, Type 2 / blood
  • Diabetes Mellitus, Type 2 / drug therapy*
  • Double-Blind Method
  • Female
  • Glycated Hemoglobin A / analysis
  • Humans
  • Hypoglycemia / chemically induced
  • Hypoglycemia / prevention & control*
  • Hypoglycemic Agents / adverse effects
  • Hypoglycemic Agents / therapeutic use*
  • Insulin Glargine / adverse effects
  • Insulin Glargine / therapeutic use*
  • Insulin, Long-Acting / adverse effects
  • Insulin, Long-Acting / therapeutic use*
  • Male
  • Middle Aged
  • Risk Factors

Substances

  • Blood Glucose
  • Glycated Hemoglobin A
  • Hypoglycemic Agents
  • Insulin, Long-Acting
  • Insulin Glargine
  • insulin degludec

Associated data

  • ClinicalTrials.gov/NCT02030600