Effect of Insulin Degludec vs Insulin Glargine U100 on Hypoglycemia in Patients With Type 2 Diabetes: The SWITCH 2 Randomized Clinical Trial.
|Abstract||Hypoglycemia, a serious risk for insulin-treated patients with type 2 diabetes, negatively affects glycemic control.|
Insulin degludec, an ultra-longacting basal insulin, versus insulin glargine in basal-bolus treatment with mealtime insulin aspart in type 2 diabetes (BEGIN Basal-Bolus Type 2): a phase 3, randomised, open-label, treat-to-target non-inferiority trial.
|Publication Year Start||2017-01-01|
PMID- 28672317 OWN - NLM STAT- In-Process DA - 20170703 LR - 20170703 IS - 1538-3598 (Electronic) IS - 0098-7484 (Linking) VI - 318 IP - 1 DP - 2017 Jul 04 TI - Effect of Insulin Degludec vs Insulin Glargine U100 on Hypoglycemia in Patients With Type 2 Diabetes: The SWITCH 2 Randomized Clinical Trial. PG - 45-56 LID - 10.1001/jama.2017.7117 [doi] AB - 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. FAU - Wysham, Carol AU - Wysham C AD - Rockwood Clinic, University of Washington School of Medicine, Spokane. FAU - Bhargava, Anuj AU - Bhargava A AD - Iowa Diabetes and Endocrinology Research Center, Des Moines. FAU - Chaykin, Louis AU - Chaykin L AD - Meridien Research, Bradenton, Florida. FAU - de la Rosa, Raymond AU - de la Rosa R AD - Paducah Endocrinology, Paducah, Kentucky. FAU - Handelsman, Yehuda AU - Handelsman Y AD - Metabolic Institute of America, Tarzana, California. FAU - Troelsen, Lone N AU - Troelsen LN AD - Medical and Science, Novo Nordisk, Soborg, Denmark. FAU - Kvist, Kajsa AU - Kvist K AD - Biostatistics Insulin and Diabetes Outcomes, Novo Nordisk, Soborg, Denmark. FAU - Norwood, Paul AU - Norwood P AD - Valley Research, Fresno, California. LA - eng PT - Journal Article PL - United States TA - JAMA JT - JAMA JID - 7501160 EDAT- 2017/07/04 06:00 MHDA- 2017/07/04 06:00 CRDT- 2017/07/04 06:00 AID - 2635630 [pii] AID - 10.1001/jama.2017.7117 [doi] PST - ppublish SO - JAMA. 2017 Jul 4;318(1):45-56. doi: 10.1001/jama.2017.7117.