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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 T2DM1

Background

Stratification by :

  • Hb1A1c at screening (<8.0/≥8.0 % [<64/≥64 mmol/mol])
  • Use of SU or meglitinides at screening (Yes/No)

aWith the exception of a maximum of 8 consecutive days or 15 days total during the last year prior insulin use

Overall baseline characteristics were similar between treatment groups1

 

Gla-300

n=466

IDeg-100

n=463
Known T2DM duration, years 10.5 ± 6.1 10.7 ± 6.5
HbA1c % 8.7 ± 0.8 8.6 ± 0.8

Randomised population. Data expressed as mean ± standard deviation unless stated otherwise

Background therapies were not changed during the study unless safety concerns necessitated dose reduction or discontinuation.1

Gla-300: insulin glargine 300 U/mL; IDeg-100: insulin degludec 100 U/mL; PK: pharmacokinetic; PD: pharmacodynamic; RCT: randomized clinical trial; T2DM: type 2 diabetes mellitus; T1DM: type 1 diabetes mellitus; BMI: body mass index; SGLT2: sodium-glucose cotransporter-2; GLP-1 RA: glucagon-like peptide-1 receptor agonist; OAD: oral antihyperglycemic drug; SMPG: self-monitored plasma glucose; SU: sulfonylureas 

Pre-defined endpoints1

Primary efficacy endpoint:

Change in HbA1c from baseline to week 24

  • Analysed using a MMRM approach, adjusted for covariates including baseline HbA1c
  • Non-inferiority margin was 0.3 % (HbA1c units)

Secondary efficacy endpoints:

  • Change in FPG, fasting SMPG, and eight-point SMPG profiles from baseline to week 24
  • Change in variability of 24-h SMPG, based on eight-point profiles
  • Percentage of participants reaching target HbA1c <7.0% (<53 mmol/mol) at week 24
  • Percentage of participants reaching target HbA1c <7.0% (<53 mmol/mol) at week 24 without confirmed hypoglycemia (≤70 mg/dL and <54 mg/dL)

Safety endpoints:

The incidence and event rates of hypoglycemia during the 24-week on-treatment period, the active titration period (weeks 0–12), and the maintenance period (weeks 13–24).

  • Body weight and adverse events (AEs).

Results

Primary efficacy endpoint:

Non-inferiority of Gla-300 vs IDeg-100 in HbA1c reduction at study end1

LS mean difference for Gla-300 vs IDeg-100: -0.05% (95% CI -0.15 to 0.05) (-0.6 mmol/mol [-1.7 to 0.6]), non-inferiority p-value <0.0001

Secondary efficacy endpoints:

FPG and fasting SMPG reduction with Gla-300 vs IDeg-100 from baseline to study end1

FPG LS mean difference from baseline to week 24 for Gla-300 vs IDeg-100: 7.7 mg/dL (95% CI: 2.7–12.7)

Fasting SMPG LS mean difference from baseline to week 24 for Gla-300 vs IDeg-100: 1.1 mg/dL (95% CI: -1.9 to 4.1)

Similar 8-point (24-hr SMPG) variability profiles between both groups at baseline and study end1

Similar variability of 24-h SMPG at baseline and week 24 with both treatments.1

8-point SMPG profiles

Within-day plasma glucose variability

Safety endpoints:

Treatment-emergent adverse events1

  • Individual agents offer CV and/or renal protection beyond blood pressure lowering alone.1,2,3
  • 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 (female, 49 years old, treated with metformin).

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.1 Safety population (Gla-300, n=462; IDeg-100, n=462)3

FPG: fasting plasma glucose; MMRM: mixed model for repeated measurements; BL: baseline; LS: Least square; SE: standard error; W: week; CI: confidence interval; SD: standard deviation

Findings:

Confirmed hypoglycemia (≤3.9 mmol/L) incidence by time of day4

Background antihyperglycemic therapies had no impact on the comparable efficacy and hypoglycemia profiles of Gla-300 and IDeg-100.5

Mean daily insulin doses3

Mean (± SD) change in body weight from baseline to week 241

Gla-300

  • 2.0 kg (±3.8)

IDeg -100

  • 2.3 kg (±3.6)

Clinical implications

  • Comparable glycemic control was achieved alongside similarly low overall incidence and rates of hypoglycemia in both insulin groups throughout the treatment period.1

  • According to the ADA 2022 Guidelines for Medical Care in Diabetes, insulin doses should be titrated to meet individualized glycemic targets and to avoid hypoglycemia.6

  • Patients who experience hypoglycemia soon after initiating basal insulin are at greater risk of discontinuation of their basal insulin therapy and hospitalization than those who remain free of hypoglycemic events.7

  • Glycaemic control and hypoglycaemia incidence at 3 months were associated with long-term glycaemic control and hypoglycaemia incidence, respectively.8

  • Gla-300 was associated with lower incidence and rates of anytime (24-h) confirmed hypoglycemia ≤70 and <54 mg/dL) than IDeg-100 during the 0–12-week period when most of the insulin dose titration and plasma glucose reduction occurred.1

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
  • No difference between treatments over 24 weeks was seen in the incidence of confirmed hypoglycemia at the <54 mg/dL threshold.1
  • Lower incidence and annualized rates of anytime (24-h) confirmed hypoglycemia (≤70 and <54 mg/dL) were observed with Gla-300 versus IDeg-100 during the inial titration period (0–12 weeks).1

ADA: American Diabetes Association

References

  1. Rosenstock J, Cheng A, Ritzel R, et al. More Similarities Than Differences Testing Insulin Glargine 300 Units/mL Versus Insulin Degludec 100 Units/mL in Insulin-Naive Type 2 Diabetes: The Randomized Head-to-Head BRIGHT Trial. Diabetes Care. 2018;41(10):2147-2154.

  2. Becker RH, Dahmen R, Bergmann K, Lehmann A, Jax T, Heise T. New insulin glargine 300 Units · mL-1 provides a more even activity profile and prolonged glycemic control at steady state compared with insulin glargine 100 Units · mL-1. Diabetes Care. 2015;38(4):637-43.

  3. Rosenstock J, Cheng A, Ritzel R, et al. More Similarities Than Differences Testing Insulin Glargine 300 Units/mL Versus Insulin Degludec 100 Units/mL in Insulin-Naive Type 2 Diabetes: The Randomized Head-to-Head BRIGHT Trial. Diabetes Care. 2018;41(10):2147-2154.

  4. Cheng A, Harris S, Giorgino F, et al. Similar glycaemic control and less hypoglycaemia during active titration after insulin initation with glargine 300 units/mL and degludec 100 units/mL: A subanalysis of the BRIGHT study. Diabetes Obes Metab. 2020;22(3):346-354.

  5. Roussel R, Rosenstock J, Pettuus J, et al. Impact of background antihyperglycemic therapy on insulin glargine 300 U/mL (Gla-300) vs. insulin degludec 100 U/mL (IDeg-100) in insulin-naïve people with T2DM from the BRIGHT randomized study. Diabetes. 2018;67(Supplement_1).

  6. American Diabetes Association. Standards of Medical Care in Diabetes—2022. Diabetes Care. 2022;45(Suppl 1):S1-2. Available at: https://a- da.silverchair-cdn.com/ada/content_public/journal/- care/issue/45/supplement_1/6/standards-of-care-2022-copyright-stamped-updated-01062022.pdf?Expires=1644932281&Signature=0seWKx jFTTRBey4ApIGXg-Cv9TVjkb1zugZm-PqSfz40jDh9IfaJhjzAa5LofV7vA-jZMBUie9ZtRjtvKsihp3AYn4PC6yBgK4j5reixQz8QyZSlp5Jrjo245zTqtAUWn VgQoJxpWakdhuKYnwOS8OKQTzLdQXR8Rj~rwTFoHNNKhuC04LhJ3nR0mh4ykblD~G2adicbyVG-PDRWaOY6x~qHlbJ1YPV0KeDaeXayqneJkV5W azu9AlZZvBcxbnUja9PyHSmS~7UAL-4xktkzPMwFpWy5ABZSl-c51~v5g2GZtWy6t-E3frDE7NdfHdxnlinpJh~Fo1wGVHKK46VDnw__&Key-Pair-Id= APKAIE5G5CRDK6RD3PGA. Last accessed: 8/2/2022.

  7. Dalal MR, Kazemi MR, Ye F. Hypoglycemia in patients with type 2 diabetes newly initiated on basal insulin in the US in a community setting: impact on treatment discontinuation and hospitalization. Curr Med Res Opin. 2017;33(2):209-214.

  8. Mauricio D, Meneghini L, Seufert J, et al. Glycaemic control and hypoglycaemia burden in patients with type 2 diabetes initiating basal insulin in Europe and the USA. Diabetes Obes Metab. 2017;19(8):1155-1164.

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