The Bright Study
The first head-to-head RCT designed to compare the efficacy and safety of Gla-300 with IDeg-100 in participants with T2DM.
Background
However, direct clinical comparisons between these two-2nd generation basal insulin analogues are not available.
Study Design⁵
Multicentre, open-label, 1:1 randomised, active-controlled, 2-arm parallel-group, non-inferiority study in adult participants with uncontrolled T2DM
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Gla-300 and IDeg-100 were self-administered once daily between 18:00–20:00 h5
Titrated weekly to target fasting SMPG of 4.4–5.6 mmol/L (80–100 mg/dL)
without hypoglycaemia5
Titration performed with aim of target achievement within 8–12 weeks post
randomisation (titration period)5
ᵃDoses titrated at least weekly
aWith the exception of a maximum of 8 consecutive days or 15 days total prior insulin use
Pre-Defined Endpoints⁵
Primary efficacy endpoint:
Change in HbA1c from baseline to week 24
- Analysed using a MMRM approach, adjusted for covariates including baseline HbA1c
Secondary efficacy endpoints:
-
Change in HbA1c and fasting SMPG from baseline to week 12
-
Change in FPG, fasting SMPG and 8-point SMPG profiles from baseline to week 24
-
Variability of 8-point SMPG profiles
Safety endpoints:
-
Incidence and annualised rates of confirmed hypoglycaemia (≤3.9 and <3.0 mmol/L) over the full 24-week period, and during weeks 0–12 (titration period) and weeks 13–24 (maintenance period)
-
TEAEs
Results
Primary efficacy endpoints:
Non-inferiority of Gla-300 vs IDeg-100 in HbA1c reduction at study end⁵
Secondary efficacy endpoints:
FPG and fasting SMPG reduction with Gla-300 vs IDeg-100 from baseline to study end⁵
Similar 8-point SMPG and variability profiles at baseline and study end⁵
Similar variability of 24-h SMPG and fasting SMPG at baseline and week 24 with both treatments.⁵
| Mean CV, % | Gla-300 | IDeg-100 |
| 24-h SMPG |
|
|
| Baseline | 22.5 | 23.4 |
| Week 24 | 27.6 | 28.0 |
| LS mean change | 3.7 | 4.0 |
| Fasting SMPG |
|
|
| Baseline | 13.8 | 14.6 |
| Week 24 | 16.5 | 17.0 |
| LS mean change | 1.5 | 2.0 |
Safety endpoints:
Incidence (%) and events per patient-year of confirmed (≤3.9 mmol/l) during titration period⁵
Treatment-emergent adverse events⁵
-
No specific safety concerns were reported
-
There was one death in the Gla-300 group (adenocarcinoma of the colon)
-
Only one episode of severe hypoglycemia occurred during the entire study.
Confirmed hypoglycaemia included documented symptomatic or asymptomatic hypoglycaemia (≤70 mg/dL or <54 mg/dL), and severe events if any; only 1 participant experienced severe hypoglycaemia (1 event), in the Gla-300 group, due to a skipped evening meal and not reducing her insulin dose after a non-severe event 2 days earlier. All p-values presented are nominal. Safety population (Gla-300, n=463; IDeg-100, n=462)⁵
Findings:
Hypoglycemia incidence by time of day⁷
Comparable glycaemic control and hypoglycaemia incidence over 24 weeks, regardless of SU/glinide use at screening⁶
ᵃp value to test heterogeneity of treatment-by-subgroup interaction. HbA1c reduction assessed in ITT population; hypoglycemia incidence assessed in safety population
Clinical Implications
-
Gla-300 and IDeg-100 provide similar glycaemic control accompanied by comparable hypoglycaemia⁵
-
Active and adequate titration can help patients achieve glycaemic goals – dose increases are associated with improved HbA1c levels⁸
-
Early hypoglycaemic events during titration are associated with increased rates of treatment discontinuation, as well as long-term risk of hypoglycaemia⁹,¹⁰
-
Gla-300 may offer an advantage in hypoglycaemia risk reduction vs IDeg-100 during the titration period in insulin-naïve patients with T2DM⁵
Conclusion
-
Bright was the first direct comparison of Gla-300 vs IDeg-100:
-
Similar glycaemic control for HbA1c and fasting SMPG
-
Similar variability in 24-h SMPG and fasting SMPG
-
-
During the full study and maintenance periods, anytime and nocturnal confirmed hypoglycaemia were comparable
-
During the titration period (0–12 weeks), the rate of anytime and nocturnal confirmed hypoglycaemia were lower with Gla-300 vs IDeg-100
