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

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

Wysham C(1), Bhargava A(2), Chaykin L(3), de la Rosa R(4), Handelsman Y(5),
Troelsen LN(6), Kvist K(7), Norwood P(8).

Author information: 
(1)Rockwood Clinic, University of Washington School of Medicine, Spokane.
(2)Iowa Diabetes and Endocrinology Research Center, Des Moines.
(3)Meridien Research, Bradenton, Florida.
(4)Paducah Endocrinology, Paducah, Kentucky.
(5)Metabolic Institute of America, Tarzana, California.
(6)Medical and Science, Novo Nordisk, Søborg, Denmark.
(7)Biostatistics Insulin and Diabetes Outcomes, Novo Nordisk, Søborg, Denmark.
(8)Valley Research, Fresno, California.

Comment in
    JAMA. 2017 Jul 4;318(1):31-32.

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.

DOI: 10.1001/jama.2017.7117 
PMCID: PMC5817473
PMID: 28672317  [Indexed for MEDLINE]