Effect of Insulin Degludec vs Insulin Glargine U100 on Hypoglycemia in Patients With Type 1 Diabetes: The SWITCH 1 Randomized Clinical Trial.
|Abstract||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.|
Comparison of insulin detemir and insulin glargine in a basal-bolus regimen, with insulin aspart as the mealtime insulin, in patients with type 1 diabetes: a 52-week, multinational, randomized, open-label, parallel-group, treat-to-target noninferiority trial.
|Publication Year Start||2017-01-01|
PMID- 28672316 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 1 Diabetes: The SWITCH 1 Randomized Clinical Trial. PG - 33-44 LID - 10.1001/jama.2017.7115 [doi] AB - 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. FAU - Lane, Wendy AU - Lane W AD - Mountain Diabetes and Endocrine Center, Asheville, North Carolina. FAU - Bailey, Timothy S AU - Bailey TS AD - AMCR Institute, Escondido, California. FAU - Gerety, Gregg AU - Gerety G AD - Albany Medical College, Albany, New York. FAU - Gumprecht, Janusz AU - Gumprecht J AD - Medical University of Silesia, Zabrze, Poland. FAU - Philis-Tsimikas, Athena AU - Philis-Tsimikas A AD - Scripps Whittier Diabetes Institute, San Diego, California. FAU - Hansen, Charlotte Thim AU - Hansen CT AD - Medical & Science, Novo Nordisk A/S, Soborg, Denmark. FAU - Nielsen, Thor S S AU - Nielsen TSS AD - Biostatistics Insulin & Diabetes Outcomes, Novo Nordisk A/S, Soborg, Denmark. FAU - Warren, Mark AU - Warren M AD - Physicians East PA, Greenville, North Carolina9School of Osteopathic Medicine, Campbell University, Lillington, North Carolina. CN - Group Information CN - SWITCH 1 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 - 2635629 [pii] AID - 10.1001/jama.2017.7115 [doi] PST - ppublish SO - JAMA. 2017 Jul 4;318(1):33-44. doi: 10.1001/jama.2017.7115.