Insulin Degludec Administered at the Same Time Each Day in Combination with a Rapid-Acting Insulin Analog at Mealtimes in Adult Patients

Study A

The efficacy of Insulin Degludec was evaluated in a 52-week randomized, open-label, multicenter trial in 629 patients with type 1 diabetes mellitus (Study A). Patients were randomized to Insulin Degludec once-daily with the evening meal or insulin glargine U-100 once-daily according to the approved labeling. Insulin aspart was administered before each meal in both treatment arms. 

The mean age of the trial population was 43 years and mean duration of diabetes was 19 years. 59% were male. 93% were White, 2% Black or African American. 5% were Hispanic. 9% of patients had eGFR<60 mL/min/1.73m2. The mean BMI was approximately 26.3 kg/m2. 

At week 52, the difference in HbA1c reduction from baseline between Insulin Degludec and insulin glargine U-100 was -0.01% with a 95% confidence interval of [-0.14%; 0.11%] and met the pre-specified non-inferiority margin (0.4%). See Table 6, Study A.

Study B

The efficacy of Insulin Degludec was evaluated in a 26-week randomized, open-label, multicenter trial in 455 patients with type 1 diabetes mellitus (Study B). Patients were randomized to Insulin Degludec or insulin detemir once-daily in the evening. After 8 weeks, insulin detemir could be dosed twice-daily. 67% used insulin detemir once daily at end of trial. 33% used insulin detemir twice daily at end of trial. Insulin aspart was administered before each meal in both treatment arms. 

The mean age of the trial population was 41 years and mean duration of diabetes was 14 years. 52% were male. 45% were White, 0.4% Black or African American. 4% were Hispanic. 4% of patients had eGFR<60 mL/min/1.73m2. The mean BMI was approximately 23.9 kg/m2. 

At week 26, the difference in HbA1c reduction from baseline between Insulin Degludec and insulin detemir was -0.09% with a 95% confidence interval of [-0.23%; 0.05%] and met the pre-specified non-inferiority margin (0.4%). See Table 6, Study B.

Table 6: Results at Week 52 in a Trial Comparing Insulin Degludec to Insulin Glargine U-100 (Study A) and Week 26 in a Trial Comparing Insulin Degludec to Insulin Detemir (Study B) in Adult Patients with Type 1 Diabetes Mellitus Receiving Insulin Aspart at Mealtimes

     1At Week 52 
     2At Week 26 
     *The change from baseline to end of treatment visit in HbA1c was analyzed using ANOVA with treatment, region, sex, and anti-diabetic treatment at screening as fixed effects, and age and baseline HbA1c as covariates. 
    In Study A, there were 14.8% of subjects in the Insulin Degludec and 11.5% Insulin glargine arms for whom data was missing at the time of the HbA1c measurement.
    In Study B, there were 6.3% of subjects in the Insulin Degludec and 9.8% Insulin detemir arms for whom data was missing at the time of the HbA1c measurement.

Study C: Insulin Degludec Administered at the Same Time Each Day or at Any Time Each Day in Combination with a Rapid-Acting Insulin Analog at Mealtimes in Adult Patients

The efficacy of Insulin Degludec was evaluated in a 26-week randomized, open-label, multicenter trial in 493 patients with type 1 diabetes mellitus. Patients were randomized to Insulin Degludec injected once-daily at the same time each day (with the main evening meal), to Insulin Degludec injected once daily at any time each day or to insulin glargine U-100 injected once-daily according to the approved labeling. The any time each day Insulin Degludec arm was designed to simulate a worst-case scenario injection schedule of alternating short and long, once daily, dosing intervals (i.e., alternating intervals of 8 to 40 hours between doses). Insulin Degludec in this arm was dosed in the morning on Monday, Wednesday, and Friday and in the evening on Tuesday, Thursday, Saturday, and Sunday. Insulin aspart was administered before each meal in all treatment arms. 

The mean age of the trial population was 44 years and mean duration of diabetes was 19 years. 58% were male. 98% were White, 2% Black or African American. 3% were Hispanic. 7% of patients had eGFR<60 mL/min/1.73m2. The mean BMI was approximately 26.7 kg/m2. 

At week 26, the difference in HbA1c reduction from baseline between Insulin Degludec administered at alternating times and insulin glargine U-100 was 0.17% with a 95% confidence interval of [0.04%; 0.30%] and met the pre-specified non-inferiority margin (0.4%). See Table 7.

Table 7: Results at Week 26 in a Trial Comparing Insulin Degludec Dosed Once Daily at the Same and at Alternating Times Each Day to Insulin Glargine U-100 in Adult Patients with Type 1 Diabetes Mellitus Receiving Insulin Aspart at Mealtimes

*The change from baseline to end of treatment visit in HbA1c was analyzed using ANOVA with treatment, region, sex, and anti-diabetic treatment at screening as fixed effects, and age and baseline HbA1c as covariates.

In Study C, there were 15.8% and 15.9% of subjects in the Insulin Degludec (same time and alternating times respectively) and 7.9% Insulin glargine arms for whom data was missing at the time of the HbA1c measurement.