Tresiba (Page 6 of 9)
14.2 Type 1 Diabetes – Pediatric Patients 1 Year of Age and Older
Study J: TRESIBA Administered at the Same Time Each Day in Combination with a Rapid-Acting Insulin Analog at Mealtimes in Pediatric Patients 1 Year of Age and Older
The efficacy of TRESIBA was evaluated in a 26-week, randomized, open label, multicenter trial in 350 patients with type 1 diabetes mellitus (Study J). Patients were randomized to TRESIBA once-daily or insulin detemir once or twice-daily. Subjects on a twice-daily insulin detemir regimen were dosed at breakfast and in the evening either with the main evening meal or at bedtime. Insulin aspart was administered before each main meal in both treatment arms. At end of trial, 36% used insulin detemir once daily and 64% used insulin detemir twice daily.
The mean age of the trial population was 10 years; 24% were ages 1-5 years; 39% were ages 6-11 years and 36% were ages 12-17 years. The mean duration of diabetes was 4 years. 55.4% were male. 74.6% were White, 2.9% Black or African American. 2.9% were Hispanic. The mean z-score for body weight was 0.31.
At week 26, the difference in HbA1c reduction from baseline between TRESIBA and insulin detemir was 0.15% with a 95% confidence interval of [-0.03%; 0.33%] and met the pre-specified non-inferiority margin (0.4%). See Table 8.
Table 8: Results at Week 26 in a Trial Comparing TRESIBA to Insulin Detemir in Pediatric Patients 1 Year of Age and Older with Type 1 Diabetes Mellitus Receiving Insulin Aspart at Mealtimes
| TRESIBA+ Insulin aspart | Insulin detemir + Insulin aspart | |
| N | 174 | 176 |
| HbA1c (%) | ||
| Baseline | 8.2 | 8.0 |
| End of 26 weeks | 8.0 | 7.7 |
| Adjusted mean change from baseline after 26 weeks ± | -0.19 | -0.34 |
| Estimated treatment difference [95%CI] TRESIBA v. Insulin detemir | 0.15 [ -0.03; 0.33] | |
| FPG (mg/dL) | ||
| Baseline | 162 | 151 |
| End of 26 weeks | 150 | 160 |
| Adjusted mean change from baseline after 26 weeks | 52.0 | 59.6 |
| Daily basal insulin dose | ||
| Baseline mean | 15 U (0.37 U/kg) | 16 U (0.41 U/kg) |
| Mean dose after 26 weeks | 16 U (0.37 U/kg) | 22 U (0.51 U/kg) |
| Daily bolus insulin dose | ||
| Baseline mean | 20 U (0.50 U/kg) | 20 U (0.52 U/kg) |
| Mean dose after 26 weeks | 23 U (0.56 U/kg) | 22 U (0.57 U/kg) |
- ± The change from baseline to end of treatment visit in HbA1c was analyzed using ANOVA with missing data imputed by multiple imputation carrying forward the baseline value and adding the error term, with treatment, region, sex, and age group as fixed factors, and baseline HbA1c as covariate.
- In Study J, there were 2.9% of subjects in TRESIBA and 6.3% Insulin detemir arms for whom data was missing at the 26-week HbA1c measurement.
14.3 Type 2 Diabetes — Adult
Study D: TRESIBA Administered at the Same Time Each Day as an Add-on to Metformin with or without a DPP-4 Inhibitor in Insulin Naïve Adult Patients
The efficacy of TRESIBA was evaluated in a 52-week randomized, open-label, multicenter trial that enrolled 1030 insulin naïve patients with type 2 diabetes mellitus inadequately controlled on one or more oral antidiabetic agents (OADs). Patients were randomized to TRESIBA once-daily with the evening meal or insulin glargine U-100 once-daily according to the approved labeling. Metformin alone (82.5%) or in combination with a DPP-4 inhibitor (17.5%) was used as background therapy in both treatment arms.
The mean age of the trial population was 59.1 years and mean duration of diabetes was 9.2 years. 61.9% were male. 88.4% were White, 7.1% Black or African American. 17.2% were Hispanic. 9.6% of patients had eGFR<60 mL/min/1.73m2. The mean BMI was approximately 31.1 kg/m2.
At week 52, the difference in HbA1c reduction from baseline between TRESIBA and insulin glargine U-100 was 0.09% with a 95% confidence interval of [-0.04%; 0.22%] and met the pre-specified non-inferiority margin (0.4%); See Table 9.
Table 9: Results at Week 52 in a Trial Comparing TRESIBA to Insulin Glargine U-100 in Adult Patients with Type 2 Diabetes Mellitus on OAD(s)*
| TRESIBA + OAD(s)* | Insulin glargine U-100 + OAD(s)* | ||
| N | 773 | 257 | |
| HbA1c (%) | |||
| Baseline | 8.2 | 8.2 | |
| End of trial | 7.1 | 7.0 | |
| Adjusted mean change from baseline** | -1.06 | -1.15 | |
| Estimated treatment difference [95%CI] TRESIBA — Insulin glargine U-100 | 0.09 [-0.04;0.22] | ||
| Proportion Achieving HbA1c < 7% at Trial End | 51.7% | 54.1% | |
| FPG (mg/dL) | |||
| Baseline | 174 | 174 | |
| End of trial | 106 | 115 | |
| Adjusted mean change from baseline | -68.0 | -60.2 | |
| Daily insulin dose | |||
| Baseline mean (starting dose) | 10 U | 10 U | |
| Mean dose after 52 weeks | 56 U | 58 U | |
- * OAD: oral antidiabetic agent
- ** 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 D, there were 20.6% of subjects in the TRESIBA and 22.2% Insulin glargine arms for whom data was missing at the time of the HbA1c measurement.
Study E: TRESIBA U-200 Administered at the Same Time Each Day as an Add-on to Metformin with or without a DPP-4 Inhibitor in Insulin Naïve Adult Patients
The efficacy of TRESIBA U-200 was evaluated in a 26-week randomized, open-label, multicenter trial in 457 insulin naïve patients with type 2 diabetes mellitus inadequately controlled on one or more oral antidiabetic agents (OADs) at baseline. Patients were randomized to TRESIBA U-200 once-daily with the evening meal or insulin glargine U-100 once-daily according to the approved labeling. Both treatment arms were receiving metformin alone (84%) or in combination with a DPP-4 inhibitor (16%) as background therapy.
The mean age of the trial population was 57.5 years and mean duration of diabetes was 8.2 years. 53.2% were male. 78.3% were White, 13.8% Black or African American. 7.9% were Hispanic. 7.5% of patients had eGFR <60 mL/min/1.73m2. The mean BMI was approximately 32.4 kg/m2.
At week 26, the difference in HbA1c reduction from baseline between TRESIBA U-200 and insulin glargine U-100 was 0.04% with a 95% confidence interval of [-0.11%; 0.19%] and met the pre-specified non-inferiority margin (0.4%). See Table 10.
Table 10: Results at Week 26 in a Trial Comparing TRESIBA U-200 to Insulin Glargine U-100 in Adult Patients with Type 2 Diabetes Mellitus on OAD(s)*
| TRESIBA U-200 + Met ± DPP-4 | Insulin glargine U-100 + Met ± DPP-4 | ||
| N | 228 | 229 | |
| HbA1c (%) | |||
| Baseline | 8.3 | 8.2 | |
| End of trial | 7.0 | 6.9 | |
| Adjusted mean change from baseline** | -1.18 | -1.22 | |
| Estimated treatment difference [95%CI] TRESIBA — Insulin glargine U-100 | 0.04 [-0.11;0.19] | ||
| Proportion Achieving HbA1c < 7% at Trial End | 52.2% | 55.9% | |
| FPG (mg/dL) | |||
| Baseline | 172 | 174 | |
| End of trial | 106 | 113 | |
| Adjusted mean change from baseline | -71.1 | -63.5 | |
| Daily insulin dose | |||
| Baseline mean | 10 U | 10 U | |
| Mean dose after 26 weeks | 59 U | 62 U | |
- * OAD: oral antidiabetic agent
- ** 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 E, there were 12.3% of subjects in the TRESIBA and 12.7% Insulin glargine arms for whom data was missing at the time of the HbA1c measurement.
Study F: TRESIBA Administered at the Same Time Each Day in Insulin Naïve Adult Patients as an Add-on to One or More of the Following Oral Agents: Metformin, Sulfonylurea, Glinides or Alpha-Glucosidase Inhibitors
The efficacy of TRESIBA was evaluated in a 26-week randomized, open-label, multicenter trial in Asia in 435 insulin naïve patients with type 2 diabetes mellitus inadequately controlled on one or more oral antidiabetic agents (OADs) at baseline. Patients were randomized to TRESIBA once-daily in the evening or insulin glargine U-100 once-daily according to the approved labeling. Pre-trial oral antidiabetes agents were continued as background therapy except for DPP-4 inhibitors or thiazolidinediones in both treatment arms.
The mean age of the trial population was 58.6 years and mean duration of diabetes was 11.6 years. 53.6% were male. All patients were Asian. 10.9% of patients had eGFR<60 mL/min/1.73m2. The mean BMI was approximately 25.0 kg/m2.
At week 26, the difference in HbA1c reduction from baseline between TRESIBA and insulin glargine U-100 was 0.11% with a 95% confidence interval of [-0.03%; 0.24%] and met the pre-specified non-inferiority margin (0.4%). See Table 11.
Table 11: Results at Week 26 in a Trial Comparing TRESIBA to Insulin Glargine U-100 in Adult Patients with Type 2 Diabetes Mellitus on OAD(s)*
| TRESIBA + OAD(s)* | Insulin glargine U-100 + OAD(s)* | |
| N | 289 | 146 |
| HbA1c (%) | ||
| Baseline | 8.4 | 8.5 |
| End of trial | 7.2 | 7.1 |
| Adjusted mean change from baseline* * | -1.42 | -1.52 |
| Estimated treatment difference [95%CI] TRESIBA — Insulin glargine U-100 | 0.11 [-0.03 ; 0.24] | |
| Proportion Achieving HbA1c < 7% at Trial End | 40.8% | 48.6% |
| FPG (mg/dL) | ||
| Baseline | 152 | 156 |
| End of trial | 100 | 102 |
| Adjusted mean change from baseline | -54.6 | -53.0 |
| Daily insulin dose | ||
| Baseline mean (starting dose) | 9 U | 9 U |
| Mean dose after 26 weeks | 19 U | 24 U |
- * OAD: oral antidiabetic agent
- ** 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 F, there were 10% of subjects in the TRESIBA and 6.8% Insulin glargine arms for whom data was missing at the time of the HbA1c measurement.
Study G: TRESIBA Administered at the Same Time Each Day or Any Time Each Day as an Add-on to One and up to Three of the Following Oral Agents: Metformin, Sulfonylurea or Glinides or Pioglitazone in Adult Patients
The efficacy of TRESIBA was evaluated in a 26-week randomized, open-label, multicenter trial in 687 patients with type 2 diabetes mellitus inadequately controlled on basal insulin alone, oral antidiabetic agents (OADs) alone or both basal insulin and OAD. Patients were randomized to TRESIBA injected once-daily at the same time each day (with the main evening meal), to TRESIBA 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 TRESIBA 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). TRESIBA in this arm was dosed in the morning on Monday, Wednesday, and Friday and in the evening on Tuesday, Thursday, Saturday, and Sunday. Up to three of the following oral antidiabetes agents (metformin, sulfonylureas, glinides or thiazolidinediones) were administered as background therapy in both treatment arms.
The mean age of the trial population was 56.4 years and mean duration of diabetes was 10.6 years. 53.9% were male. 66.7% were White, 2.5% Black or African American. 10.6% were Hispanic. 5.8% of patients had eGFR<60 mL/min/1.73m2. The mean BMI was approximately 29.6 kg/m2.
At week 26, the difference in HbA1c reduction from baseline between TRESIBA at alternating times and insulin glargine U-100 was 0.04% with a 95% confidence interval of [-0.12%; 0.20%]. This comparison met the pre-specified non-inferiority margin (0.4%). See Table 12.
Table 12: Results at Week 26 in a Trial Comparing TRESIBA at Same and Alternating Times to Insulin Glargine U-100 in Adult Patients with Type 2 Diabetes Mellitus on OAD(s)*
| TRESIBAat the same time each day ± OAD(s)* | TRESIBA at alternating times ± OAD(s)* | Insulin glargine U-100 ± OAD(s)* | |
| N | 228 | 229 | 230 |
| HbA1c (%) | |||
| Baseline | 8.4 | 8.5 | 8.4 |
| End of trial | 7.3 | 7.2 | 7.1 |
| Adjusted mean change from baseline** | -1.03 | -1.17 | -1.21 |
| Estimated treatment difference [95%CI] TRESIBA alternating- Insulin glargine U-100 | 0.04 [-0.12;0.20] | ||
| Estimated treatment difference TRESIBA alternating – TRESIBA same | -0.13 | ||
| Proportion Achieving HbA1c < 7% at Trial End | 40.8% | 38.9% | 43.9% |
| FPG (mg/dL) | |||
| Baseline | 158 | 162 | 163 |
| End of trial | 105 | 105 | 112 |
| Adjusted mean change from baseline | -54.2 | -55.0 | -47.5 |
| Daily insulin dose | |||
| Baseline mean | 21 U | 19 U | 19 U |
| Mean dose after 26 weeks | 45 U | 46 U | 44 U |
- * OAD: oral antidiabetic agent
- ** 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 G, there were 11.4% subjects for TRESIBA (both same time and alternating times) and 11.7% Insulin glargine arms for whom data was missing at the time of the HbA1c measurement.
Study H: TRESIBA Administered at the Same Time Each Day in Combination with a Rapid-Acting Insulin Analog at Mealtimes in Adult Patients
The efficacy of TRESIBA was evaluated in a 52-week randomized, open-label, multicenter trial in 992 patients with type 2 diabetes mellitus inadequately controlled on premix insulin, bolus insulin alone, basal insulin alone, oral antidiabetic agents (OADs) alone or any combination thereof. Patients were randomized to TRESIBA once-daily with the main 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. Up to two of the following oral antidiabetes agents (metformin or pioglitazone) were used as background therapy in both treatment arms.
The mean age of the trial population was 58.9 years and mean duration of diabetes was 13.5 years. 54.2% were male. 82.9% were White, 9.5% Black or African American. 12.0% were Hispanic. 12.4% of patients had eGFR<60 mL/min/1.73m2. The mean BMI was approximately 32.2 kg/m2.
At week 52, the difference in HbA1c reduction from baseline between TRESIBA and insulin glargine U-100 was 0.08% with a 95% confidence interval of [-0.05%; 0.21%] and met the pre-specified non-inferiority margin (0.4%). See Table 13.
Table 13: Results at Week 52 in a Trial Comparing TRESIBA to Insulin Glargine U-100 in Adult Patients with Type 2 Diabetes Mellitus Receiving Insulin Aspart at Mealtimes and OADs*
| TRESIBA + Insulin aspart ± OAD(s)* | Insulin glargine U-100 + Insulin aspart ± OAD(s)* | |
| N | 744 | 248 |
| HbA1c (%) | ||
| Baseline | 8.3 | 8.4 |
| End of trial | 7.1 | 7.1 |
| Adjusted mean change from baseline** | -1.10 | -1.18 |
| Estimated treatment difference [95%CI] TRESIBA — Insulin glargine U-100 | 0.08 [-0.05;0.21] | |
| Proportion Achieving HbA1c < 7% at Trial End | 49.5% | 50.0% |
| FPG (mg/dL) | ||
| Baseline | 166 | 166 |
| End of trial | 122 | 127 |
| Adjusted mean change from baseline | -40.6 | -35.3 |
| Daily basal insulin dose | ||
| Baseline mean | 42 U | 41 U |
| Mean dose after 52 weeks | 74 U | 67 U |
| Daily bolus insulin dose | ||
| Baseline mean | 33 U | 33 U |
| Mean dose after 52 weeks | 70 U | 73 U |
- * OAD: oral antidiabetic agent
- ** 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 H, there were 16.1% of subjects in the TRESIBA and 14.5% Insulin glargine arms for whom data was missing at the time of the HbA1c measurement.
Study I: TRESIBA Administered at Any Time Each Day as an Add-on to One or Two of the Following Oral Agents: Metformin, Sulfonylurea, or Pioglitazone in Adult Patients
The efficacy of TRESIBA was evaluated in a 26-week randomized, open-label, multicenter trial in 447 patients with type 2 diabetes mellitus inadequately controlled on one or more oral antidiabetic agent (OADs) at baseline. Patients were randomized to TRESIBA once-daily at any time of day or sitagliptin once-daily according to the approved labeling. One or two of the following oral antidiabetes agents (metformin, sulfonylurea or pioglitazone) were also administered in both treatment arms.
The mean age of the trial population was 55.7 years and mean duration of diabetes was 7.7 years. 58.6% were male. 61.3% were White, 7.6% Black or African American. 21.0% were Hispanic. 6% of patients had eGFR<60 mL/min/1.73m2. The mean BMI was approximately 30.4 kg/m2.
At the end of 26 weeks, TRESIBA provided greater reduction in mean HbA1c compared to sitagliptin (p < 0.001). See Table 14.
Table 14: Results at Week 26 in a Trial Comparing TRESIBA to Sitagliptin in Adult Patients with Type 2 Diabetes Mellitus on OADs*
| TRESIBA + OAD(s)* | Sitagliptin + OAD(s)* | |
| N | 225 | 222 |
| HbA1c (%) | ||
| Baseline | 8.8 | 9.0 |
| End of trial | 7.2 | 7.7 |
| Adjusted mean change from baseline** | -1.52 | -1.09 |
| Estimated treatment difference [95%CI] TRESIBA — Sitagliptin | -0.43 [-0.61;-0.24]1 | |
| Proportion Achieving HbA1c < 7% at Trial End | 40.9% | 27.9% |
| FPG (mg/dL) | ||
| Baseline | 170 | 179 |
| End of trial | 112 | 154 |
| Adjusted mean change from baseline | -61.4 | -22.3 |
| Daily insulin dose | ||
| Baseline mean | 10 U | N/A |
| Mean dose after 26 weeks | 43 U | N/A |
- * OAD: oral antidiabetic agent
- ** 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 I, there were 20.9% of subjects in the TRESIBA and 22.5% Sitagliptin arms for whom data was missing at the time of the HbA1c measurement.
- 1 p <0.001; 1-sided p-value evaluated at 2.5% level for superiority
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