Table 2.
Design and primary findings of SWITCH 1 and SWITCH 2
| SWITCH 110 | SWITCH 211 | |
|---|---|---|
| Design | Multicentre (USA: 84 sites; Poland: 6 sites), randomized, double‐blind, two‐period crossover | Multicentre (USA: 152 sites), randomized, double‐blind, two‐period crossover |
| Participants | N = 501 adults | N = 721 adults |
| Inclusion criteria | T1D ≥52 weeks, BB regimen or CSII ≥26 weeks, HbA1c ≤10%, BMI ≤45 kg/m2, ≥1 hypoglycaemia risk factor | T2D ≥26 weeks, basal insulin ± OADs ≥26 weeks, HbA1c ≤9.5%, BMI ≤45 kg/m2, ≥1 hypoglycaemia risk factor |
| Treatment | Degludec or glargine U100 OD + mealtime IAsp (2–4 times daily) | Degludec or glargine U100 OD ± OAD(s) |
| Randomization | 1:1 to treatment sequence (degludec followed by glargine U100 or glargine U100 followed by degludec); 1:1 to morning or evening dosing | 1:1 to treatment sequence (degludec followed by glargine U100 or glargine U100 followed by degludec); 1:1 to morning or evening dosing |
| Duration | Two x 32‐week treatment periods (titration: weeks 1–16 and 32–48; maintenance: weeks 16–32 and 48–64) | Two x 32‐week treatment periods (titration: weeks 1–16 and 32–48; maintenance: weeks 16–32 and 48–64) |
| Titration BG target | Basal insulin: 4.0–5.0 mmol/L (71–90 mg/dL); IAsp: 4.0–6.0 mmol/L (71–108 mg/dL) | Basal insulin: 4.0–5.0 mmol/L (71–90 mg/dL) |
| Rate of symptomatic hypoglycaemiaa in the maintenance periodb |
Significantly lower with degludec versus glargine U100 HR: 0.89 [0.85; 0.94]95% CI, P < 0.001 |
Significantly lower with degludec versus glargine U100 HR: 0.70 [0.61; 0.80]95% CI, P < 0.001 |
| Change in HbA1c from baseline after 32 weeks of treatmentc | Non‐inferiority of degludec versus glargine U100 confirmed for both treatment periods | Non‐inferiority of degludec versus glargine U100 confirmed for both treatment periods |
Abbreviations: BB, basal–bolus; BG, blood glucose; BMI, body mass index; CI, confidence interval; CSII, continuous subcutaneous insulin infusion; glargine U100, glargine 100 units/mL; HR, hazard ratio; IAsp, insulin aspart; OAD, oral antidiabetic drug; OD, once daily; T1D, type 1 diabetes; T2D, type 2 diabetes.
Symptomatic hypoglycaemia was defined as severe (requiring third‐party assistance)23 as confirmed by an event adjudication committee or BG‐confirmed (<3.1 mmol/L [56 mg/dL]) accompanied by symptoms.
Primary endpoint; analysed using a Poisson model with patient as random effect; treatment, period, sequence, and time of dosing as fixed effects; and logarithm of the observation time (100 years) as offset.
Analysed separately for each treatment period with a mixed model for repeated measurements including treatment, visit, sex, region, pre‐trial insulin regimen, and time of dosing as fixed effects, and age and baseline HbA1c as covariates; all fixed factors and covariates are nested within visit.