rom rats dosed with insulin degludec and no treatment related changes in the female mammary gland cell proliferation were found using BrdU incorporation. Further, no treatment related changes in the occurrence of hyperplastic or neoplastic lesions were seen in other tissues in animals dosed with insulin degludec when compared to vehicle or human insulin.
Genotoxicity testing of insulin degludec was not performed.
In a combined fertility and embryo-fetal study in male and female rats, treatment with insulin degludec up to 21 U/kg/day (approximately 5 times the human subcutaneous dose of 0.75 U/kg/day, based on U/body surface area) prior to mating and in female rats during gestation had no effect on mating performance and fertility.
14 CLINICAL STUDIES
The efficacy of TRESIBA administered once-daily either at the same time each day or at any time each day in patients with type 1 diabetes and used in combination with a mealtime insulin was eva luated in three randomized, open-label, treat-to-target, active-controlled, trials. The efficacy of TRESIBA administered once-daily either at the same time each day or at any time each day in patients with type 2 diabetes and used in combination with a mealtime insulin or in combination with common oral anti-diabetic agents was eva luated in six randomized, open-label, treat-to-target active-controlled trials.
Patients treated with TRESIBA achieved levels of glycemic control similar to those achieved with LANTUS (insulin glargine 100 U/mL) and LEVEMIR (insulin detemir) and achieved statistically significant improvements compared to sitagliptin.
14.1 Type 1 Diabetes – AdultTRESIBA Administered at the Same Time each Day in Combination with a Rapid-Acting Insulin Analog at Mealtimes
Study A
The efficacy of TRESIBA was eva luated in a 52-week randomized, open-label, multicenter trial in 629 patients with type 1 diabetes mellitus (Study A). Patients were randomized to TRESIBA 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 18.9 years. 58.5% were male. 93% were White, 1.9% Black or African American. 5.1% were Hispanic. 8.6% 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 TRESIBA 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 TRESIBA was eva luated in a 26-week randomized, open-label, multicenter trial in 455 patients with type 1 diabetes mellitus (Study B). Patients were randomized to TRESIBA or insulin detemir once-daily in the evening. After 8 weeks, insulin detemir could be dosed twice-daily. 67.1% used insulin detemir once daily at end of trial. 32.9% 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 41.3 years and mean duration of diabetes was 13.9 years. 51.9% were male. 44.6% were White, 0.4% Black or African American. 4.4% were Hispanic. 4.4% 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 betwe
