NCT02738151: BRIGHT

Efficacy and Safety of Toujeo® Versus Tresiba® in Insulin-Naive Patients With Type 2 Diabetes Mellitus Inadequately Controlled With Oral Antihyperglycemic Drug(s) ± GLP-1 Receptor Agonist

Completed Phase 4 Results posted Last updated 14 September 2018

What this trial tests

Phase 4 trial testing Insulin glargine, 300U/mL in Diabetes Mellitus, Type 2 in 929 participants. Completed in 15 August 2017.

Timeline

19 May 2016

Primary endpoint
15 August 2017

15 August 2017

Quick facts

Lead sponsor	Sanofi
Phase	Phase 4
Status	Completed
Study type	INTERVENTIONAL
Allocation	randomized
Design	parallel
Masking	none
Primary purpose	treatment
Enrollment	929
Start date	19 May 2016
Primary completion	15 August 2017
Estimated completion	15 August 2017
Sites	158 locations across Denmark, France, Italy, Slovakia, Greece, Serbia, Sweden, United Kingdom

Drugs / interventions tested

• Insulin glargine, 300U/mL — full drug profile →
• Insulin degludec, 100 U/mL
• Non-insulin anti-diabetic treatment — full drug profile →

Conditions studied

• Diabetes Mellitus, Type 2 — all drugs for Diabetes Mellitus, Type 2 →

Sponsor

Sanofi — full company profile →

Who can join

18 and older, any sex, with Diabetes Mellitus, Type 2. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Change From Baseline in HbA1c to Week 24 Primary · Baseline, Week 24

Change in HbA1c was calculated by subtracting baseline value from Week 24 value. Adjusted Least Square (LS) means and standard errors were obtained from a mixed-effect model with repeated measures (MMRM) to account for missing data, using all post-baseline HbA1c data available during the 24-week on-treatment period.

Group	Value	95% CI
Toujeo	-1.64	± 0.037
Tresiba	-1.59	± 0.037

Change From Baseline in HbA1c to Week 12 Secondary · Baseline, Week 12

Change in HbA1c was calculated by subtracting baseline value from Week 12 value. Adjusted least square means and standard errors were obtained from a mixed-effect model with MMRM.

Group	Value	95% CI
Toujeo	-1.37	± 0.036
Tresiba	-1.39	± 0.036

Change From Baseline in Fasting Plasma Glucose (FPG) to Week 12 and Week 24 Secondary · Baseline, Week 12 and Week 24

Change in FPG was calculated by subtracting baseline value from Week 12 and Week 24 value. Adjusted LS means were obtained from MMRM including post baseline values during the 24-week on-treatment period.

Week 12

Group	Value	95% CI
Toujeo	-3.64	± 0.099
Tresiba	-3.89	± 0.100

Week 24

Group	Value	95% CI
Toujeo	-3.52	± 0.109
Tresiba	-3.95	± 0.110

Change From Baseline in Fasting Self-Monitoring Plasma Glucose (SMPG) to Week 12 and Week 24 Secondary · Baseline, Week 12 and Week 24

Fasting SMPG was measured by the participant before breakfast and before the administration of the glucose-lowering agents once a day during the study. Adjusted LS means were obtained from MMRM including post baseline values during the 24 week on treatment period.

Week 12

Group	Value	95% CI
Toujeo	-3.26	± 0.067
Tresiba	-3.25	± 0.067

Week 24

Group	Value	95% CI
Toujeo	-3.23	± 0.067
Tresiba	-3.29	± 0.068

Change From Baseline in 8 Point SMPG Profile to Week 12 and Week 24 Per Time Point Secondary · Baseline, Week 12 and Week 24

8-point SMPG profiles were measured at the following 8 points: 03:00 at night, pre-breakfast, 2 hours after breakfast, pre-lunch, 2 hours after lunch, pre-dinner, 2 hours after dinner, and bedtime.

Week 12: 03:00 at night

Group	Value	95% CI
Toujeo	-2.77	± 3.16
Tresiba	-2.28	± 3.49

Week 12: Pre-breakfast

Group	Value	95% CI
Toujeo	-3.42	± 2.79
Tresiba	-3.00	± 2.63

Week 12: 2 hours after breakfast

Group	Value	95% CI
Toujeo	-3.20	± 4.02
Tresiba	-3.23	± 3.92

Week 12: Pre-lunch

Group	Value	95% CI
Toujeo	-2.64	± 3.90
Tresiba	-2.50	± 3.65

Week 12: 2 hours after lunch

Group	Value	95% CI
Toujeo	-2.51	± 4.15
Tresiba	-1.99	± 3.94

Week 12: Pre-dinner

Group	Value	95% CI
Toujeo	-2.04	± 3.63
Tresiba	-1.93	± 3.74

Week 12: 2 hours after dinner

Group	Value	95% CI
Toujeo	-2.32	± 4.20
Tresiba	-1.76	± 3.87

Week 12: Bedtime

Group	Value	95% CI
Toujeo	-2.44	± 4.07
Tresiba	-2.08	± 3.95

Change From Baseline in 4-point SMPG Profile to Week 12 and Week 24 Per Time Point Secondary · Baseline, Week 12 and Week 24

4-point SMPG profiles were measured at the following 4 points: prebreakfast, prelunch, predinner and bedtime.

Week 12: Pre-breakfast

Group	Value	95% CI
Toujeo	-3.41	± 2.75
Tresiba	-2.97	± 2.62

Week 12: Pre-lunch

Group	Value	95% CI
Toujeo	-2.63	± 3.88
Tresiba	-2.44	± 3.65

Week 12: Pre-dinner

Group	Value	95% CI
Toujeo	-2.03	± 3.64
Tresiba	-1.92	± 3.76

Week 12: Bedtime

Group	Value	95% CI
Toujeo	-2.41	± 4.10
Tresiba	-2.11	± 3.96

Week 24: Pre-breakfast

Group	Value	95% CI
Toujeo	-3.38	± 2.81
Tresiba	-2.99	± 2.81

Week 24: Pre-lunch

Group	Value	95% CI
Toujeo	-2.81	± 3.67
Tresiba	-2.26	± 3.92

Week 24: Pre-dinner

Group	Value	95% CI
Toujeo	-1.88	± 3.79
Tresiba	-1.86	± 4.01

Week 24: Bedtime

Group	Value	95% CI
Toujeo	-2.51	± 3.87
Tresiba	-2.10	± 4.00

Change From Baseline in 24-hour Average 8-point SMPG Profile to Week 12 and Week 24 Secondary · Baseline, Week 12 and Week 24

The 8-point SMPG profile was measured at the following 8 points: 03:00 at night, pre-breakfast, 2 hours after breakfast, pre-lunch, 2 hours after lunch, pre-dinner, 2 hours after dinner, and bedtime. Adjusted LS means were obtained from MMRM.

Week 12

Group	Value	95% CI
Toujeo	-2.57	± 0.092
Tresiba	-2.50	± 0.093

Week 24

Group	Value	95% CI
Toujeo	-2.62	± 0.094
Tresiba	-2.53	± 0.096

Change From Baseline in Variability of Fasting SMPG to Week 12 and Week 24 Secondary · Baseline, Week 12 and Week 24

Adjusted LS means were obtained from MMRM. Variability was assessed by the mean of coefficient of variation calculated over at least 3 SMPG measured during the 7 days preceding the given visit.

Week 12

Group	Value	95% CI
Toujeo	2.38	± 0.418
Tresiba	2.62	± 0.416

Week 24

Group	Value	95% CI
Toujeo	1.49	± 0.391
Tresiba	1.97	± 0.390

Change From Baseline in Variability of 24-Hour 8-Point SMPG Profiles at Week 12 and Week 24 Secondary · Baseline, Week 12 and Week 24

Adjusted LS means were obtained from MMRM.

Week 12

Group	Value	95% CI
Toujeo	4.08	± 0.562
Tresiba	4.73	± 0.561

Week 24

Group	Value	95% CI
Toujeo	3.70	± 0.588
Tresiba	3.95	± 0.599

Percentage of Participants Reaching Target HbA1c of < 7% and =<6.5% at Week 12 and Week 24 Secondary · Week 12, and Week 24

Only the post-baseline HbA1c measurements before rescue and during the 12 week and 24-week on-treatment period were considered in the analysis.

Participants who reached the target <7% at Week 12

Group	Value	95% CI
Toujeo	34.63
Tresiba	36.15

Participants who reached target <=6.5% at Week 12

Group	Value	95% CI
Toujeo	11.47
Tresiba	14.29

Participants who reached the target <7% at Week 24

Group	Value	95% CI
Toujeo	48.70
Tresiba	44.59

Participants who reached target <=6.5% at Week 24

Group	Value	95% CI
Toujeo	21.21
Tresiba	19.70

Percentage of Participants Reaching Target HbA1c <7% and =<6.5% at Week 12 and Week 24 Without Severe and/or Confirmed Hypoglycemia (70 mg/dL) Event Secondary · Week 12, and Week 24

Severe hypoglycemia was an event in which the participant required the assistance of another person to actively administer carbohydrate, glucagon, or other resuscitative actions. Severe and/or confirmed hypoglycemia event was a severe event or an event confirmed by plasma glucose =\<3.9 mmol/L (=\<70 mg/dL).

Week12: Participants who reached the target <7%

Group	Value	95% CI
Toujeo	16.45
Tresiba	13.64

Week12: Participants who reached target <=6.5%

Group	Value	95% CI
Toujeo	4.11
Tresiba	4.55

Week24: Participants who reached the target <7%

Group	Value	95% CI
Toujeo	13.42
Tresiba	12.99

Week24: Participants who reached target <=6.5%

Group	Value	95% CI
Toujeo	5.84
Tresiba	5.19

Percentage of Participants With Sulphonylurea or Meglitinide Dose Reduction/ Discontinuation Due to Hypoglycemia During 24 Weeks Treatment Period Secondary · Baseline to Week 24

Percentage of participants With Sulphonylurea or Meglitinide dose reduction/ discontinuation due to Hypoglycemia during 24 Week treatment period were reported. Only participants with Sulphonylurea or meglitinides at Screening as per actual strata were taken into account in this analysis.

Group	Value	95% CI
Toujeo	4.98
Tresiba	4.76

Adverse events — posted to ClinicalTrials.gov

Time frame: All Adverse Events were collected from signature of the informed consent form until 7 days after last treatment administration (maximum exposure: 24 Weeks).. Reporting threshold: 5%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Toujeo

Serious: 21/462 (5%)

Deaths: 1/462

Tresiba

Serious: 20/462 (4%)

Deaths: 0/462

Serious adverse events (43 terms)

Reaction	System	Toujeo	Tresiba
Acute Myocardial Infarction	Cardiac disorders	—	—
Ischaemic Stroke	Nervous system disorders	—	—
Non-Cardiac Chest Pain	General disorders	—	—
Cellulitis	Infections and infestations	—	—
Atrial Flutter	Cardiac disorders	—	—
Bradycardia	Cardiac disorders	—	—
Cardiac Arrest	Cardiac disorders	—	—
Coronary Artery Disease	Cardiac disorders	—	—
Coronary Artery Insufficiency	Cardiac disorders	—	—
Myocardial Infarction	Cardiac disorders	—	—
Ventricular Tachycardia	Cardiac disorders	—	—
Retinal Haemorrhage	Eye disorders	—	—
Gastric Ulcer	Gastrointestinal disorders	—	—
Rectal Fissure	Gastrointestinal disorders	—	—
Appendicitis	Infections and infestations	—	—
Bacterial Pyelonephritis	Infections and infestations	—	—
Diverticulitis	Infections and infestations	—	—
Pneumonia	Infections and infestations	—	—
Sepsis	Infections and infestations	—	—
Urinary Tract Infection	Infections and infestations	—	—
Meniscus Injury	Injury, poisoning and procedural complications	—	—
Osteoarthritis	Musculoskeletal and connective tissue disorders	—	—
Spinal Osteoarthritis	Musculoskeletal and connective tissue disorders	—	—
Acoustic Neuroma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	—	—
Adenocarcinoma Of Colon	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	—	—

Other adverse events (2 terms — click to expand)

Reaction	System	Toujeo	Tresiba
Viral Upper Respiratory Tract Infection	Infections and infestations	—	—
Upper Respiratory Tract Infection	Infections and infestations	—	—

Most-reported serious reactions: Acute Myocardial Infarction, Ischaemic Stroke, Non-Cardiac Chest Pain, Cellulitis, Atrial Flutter, Bradycardia, Cardiac Arrest, Coronary Artery Disease.

Data from ClinicalTrials.gov NCT02738151 adverse events section.

Sponsor's own description

Primary Objective:

To demonstrate the noninferiority in the efficacy of Toujeo® to Tresiba® in glycated hemoglobin (HbA1c) change from Baseline to Week 24.

Secondary Objectives:

Change From Baseline in HbA1c to Week 12

To assess the effects of the insulin Toujeo® in comparison with insulin Tresiba® at week 12 and week 24 on:

* Change in Fasting plasma glucose (FPG);
* Change in Fasting self-monitored plasma glucose (SMPG) and 4-point SMPG and 8-point SMPG profile;
* Percentage of participants reaching HbA1c targets \<7% or ≤6.5%;
* Percentage of participants reaching HbA1c targets \<7% or ≤6.5% without severe and/or confirmed hypoglycemia
* Frequency of occurrence and diurnal distribution of hypoglycemia by American Diabetes Association (ADA) category of hypoglycemia.

To assess the safety in each treatment group.

To assess the treatment effects in each treatment group on Patient Reported Outcomes (PRO).

Percentage of participants requiring rescue therapy.

Publications & conference data

7 peer-reviewed publications reference this trial (live from Europe PMC):

1. 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.
   Rosenstock J, Cheng A, Ritzel R, Bosnyak Z, et al · · 2018 · cited 132× · PMID 30104294 · DOI 10.2337/dc18-0559
2. Differential glycaemic control with basal insulin glargine 300 U/mL versus degludec 100 U/mL according to kidney function in type 2 diabetes: A subanalysis from the BRIGHT trial.
   Haluzík M, Cheng A, Müller-Wieland D, Westerbacka J, et al · · 2020 · cited 26× · PMID 32243043 · DOI 10.1111/dom.14043
3. Second-Generation Insulin Analogues - a Review of Recent Real-World Data and Forthcoming Head-to-Head Comparisons.
   Mauricio D, Hramiak I. · · 2018 · cited 16× · PMID 30034546 · DOI 10.17925/ee.2018.14supp1.2
4. Glycaemic control and hypoglycaemia risk with insulin glargine 300 U/mL and insulin degludec 100 U/mL in older participants in the BRIGHT trial.
   Bolli GB, Cheng A, Charbonnel B, Aroda VR, et al · · 2021 · cited 10× · PMID 33687748 · DOI 10.1111/dom.14372
5. Similar glycaemic control and less hypoglycaemia during active titration after insulin initiation with glargine 300 units/mL and degludec 100 units/mL: A subanalysis of the BRIGHT study.
   Cheng A, Harris S, Giorgino F, Seufert J, et al · · 2020 · cited 6× · PMID 31646724 · DOI 10.1111/dom.13901
6. 22nd Brazilian Diabetes Society Congress
   · 2019
7. Poster abstracts
   · 2018