Diabetes Mellitus, Type 2
Conditions
Brief summary
Primary objective: To demonstrate the superiority of insulin glargine over liraglutide in terms of percentage of patients reaching a Glycosylated Haemoglobin (HbA1c) \< 7% at the end of the comparative period (24 weeks) in Type 2 diabetic patients failing lifestyle management and oral agents Secondary objectives of the comparative period (24 weeks): \>To assess the effect of insulin glargine in comparison with liraglutide on: * HbA1c level * Percentage of patients whose HbA1c has decreased but remains \>= 7% at the end of the comparative period * Percentage of patients whose HbA1c has increased at the end of the comparative period * Fasting Plasma Glucose (FPG) * 7-point Plasma Glucose (PG) profiles * Hypoglycemia occurrence * Body weight * Adverse events Objectives of the extension period (24 weeks): \>To assess the effect of insulin glargine in patients not adequately controlled with liraglutide on: * HbA1c level * FPG * 7-point PG profiles * Hypoglycemia occurrence * Body weight * Adverse events
Detailed description
Maximum estimated study duration per patient: either 27 weeks (patients randomized to insulin glargine arm) or 51 weeks (patients randomized to liraglutide arm) broken down as follow: * A 2-week of screening period, * A 24-week comparative period, * A 24-week extension period (only for patients treated with liraglutide, not adequately controlled at the end of the comparative period), * A 1-week follow-up period
Interventions
DRUGInsulin glargine
100 Units/mL solution for injection in a pre-filled SoloStar pen
DRUGLiraglutide
6 mg/mL solution for injection in a 3-mL pre-filled pen (18mg)
DRUGMetformin
Metformin was a background treatment, mandatory for each patient randomized in the study (at the minimum dose of 1g/day). It was not supplied by the sponsor.
Sponsors
Sanofi
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
35 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
(comparative period): * Patients With Type 2 Diabetes diagnosed for at least 1 year, * Treated with lifestyle interventions and metformin at the maximum tolerated dosage (with a minimum daily dosage of 1g), either alone or in combination with an oral insulin secretagogue (sulfonylurea, glinide or DiPeptidyl Peptidase IV inhibitor), for more than 3 months, * 7.5% \< HbA1c \<= 12%, * Body Mass Index (BMI) between 25 and 40 kg/m2 inclusively, * Ability and willingness to perform PG (Plasma Glucose) self monitoring using the sponsor-provided glucose meter and to complete the patient diary, * Willingness and ability to comply with the study protocol, * Signed informed consent obtained prior to any study procedure. Inclusion criteria (extension period): * Patients treated with liraglutide (at the maximal tolerated dosage), having a mean FPG ≥ 250 mg/dL at visit 10 (Week 12) or visit 11 (Week 18), or a HbA1c≥ 7% at visit 12 (Week 24) * Dosage of metformin compliant with the inclusion criteria of visit 1 (i.e. maximum tolerated dosage, with a minimum daily dosage of 1g), and maintained stable during the comparative period.
Exclusion criteria
* Previous treatment with Glucagon Like Peptide-1 analogues or insulin in the past year (except in case of temporary treatment for gestational diabetes, surgery, hospitalization...), * Treatment with thiazolidinediones or α-Glucosidases inhibitors within 3 months prior to study entry, * Diabetes other than Type 2 diabetes (e.g. secondary to pancreatic disorders, drug or chemical agents intake), * Pregnant women (women of childbearing potential must have a negative pregnancy test at study entry and a medically approved contraceptive method), * Lactating women, * Hospitalized patients (except hospitalization for routine diabetes check-up), * Active proliferative retinopathy, as defined by a photocoagulation or vitrectomy occurrence in the 6 months prior to study entry, or any other unstable (rapidly progressing) retinopathy that may require photocoagulation or surgical treatment during the study, documented by a retina examination within 2 years prior to study entry, * Impaired renal function (creatinine clearance \< 60 mL/mn), * Impaired hepatic function (Alanine Aminotransferase, Aspartate Aminotransferase 2.5 times the upper limit of normal range), * Personal or family history of medullary thyroid carcinoma, * Multiple endocrine neoplasia syndrome type 2, * Severe gastro-intestinal disease (including inflammatory bowel disease or diabetic gastroparesis), * Congestive heart failure, * History of acute pancreatitis, * Treatment with corticosteroids with potential systemic action for more than 10 days within 3 months prior to study entry, * Alcohol or drug abuse in the past 5 years, * History of sensitivity to the study drugs or to drugs with a similar chemical structure. * Night shift worker, * Presence of any condition (medical, psychological, social or geographical), current or anticipated that would compromise the patients safety or limit the patient successful participation in the study, * Participation in a clinical trial (drug or device) within 3 months prior to study entry, * Refusal or inability to give informed consent to participate in the study, * Patient is the Investigator or any sub-Investigator, research assistant, pharmacist, study coordinator, other staff or relative thereof directly involved in the conduct of the protocol. Additional
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Patients Whose Glycosylated Haemoglobin (HbA1c) <7% at the End of the Comparative Period | week 12, week 24 | The value at the end of the comparative period was defined as the last available HbA1c value measured during the comparative period plus 14 days after the last dose of Investigational Product (i.e. last-observation-carried-forward \[LOCF\] value). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Patients Whose Glycosylated Haemoglobin (HbA1c) Has Increased at the End of the Comparative Period | baseline (week -2), week 12, week 24 | Percentage of patients with HbA1c value at end of the comparative period (LOCF) higher than HbA1c baseline value |
| Glycosylated Haemoglobin (HbA1c): Change From Baseline to the End of Comparative Period | baseline (week -2), week 12, week 24 | Change in HbA1C from baseline to the last observation carried forward (LOCF) measured during the comparative period = LOCF value - baseline value |
| Glycosylated Haemoglobin (HbA1c): Change From Beginning to the End of the Extension Period | week 24, week 36, week 48 | Change in HbA1C from beginning of the extension period (week 24) to the last observation carried forward (LOCF) measured during the extension period = LOCF value - week 24 value |
| Percentage of Patients Whose Glycosylated Haemoglobin (HbA1c) <7% at the End of the Extension Period | week 36, week 48 | Value at the end of the extension period defined as last available HbA1c value measured during the extension period (i.e. last observation carried forward (LOCF) value) |
| Self-Monitored Fasting Plasma Glucose (SMFPG) Measurements: Change From Baseline to the End of the Comparative Period | baseline (week 0), week 6, week 12, week 18, week 24 | SMFPG = mean value of Self-Monitored Fasting Plasma Glucose measurements over 3 consecutive days in the week before each visit Value at the end of the comparative period defined as last available value during the comparative period (i.e. last-observation-carried-forward \[LOCF\] value) Change = LOCF value - baseline value |
| Self-Monitored Fasting Plasma Glucose (SMFPG) Measurements: Change From Beginning to the End of the Extension Period | week 24, week 30, week 36, week 48 | SMFPG = mean value of Self-Monitored Fasting Plasma Glucose measurements over 3 consecutive days in the week before each visit Value at the end of the extension period defined as last available value during the extension period (i.e. last-observation-carried-forward \[LOCF\] value) Change = LOCF value - week 24 value |
| Self-Monitored 7-point Plasma Glucose (PG) Profile: Change From Baseline to the End of the Comparative Period | baseline (week 0), week 12, week 24 | Self-monitored 7-point plasma glucose profiles (before and 2 hours after the start of breakfast, lunch and dinner, and at bedtime) recorded on 3 consecutive days in the week before each visit Value at the end of the comparative period defined as last available value during the comparative period (i.e. last-observation-carried-forward \[LOCF\] value) Change = LOCF value - baseline value |
| Percentage of Patients Whose Glycosylated Haemoglobin (HbA1c) Has Decreased But Remains ≥7% at the End of the Comparative Period | baseline (week -2), week 12, week 24 | Percentage of patients with: \* HbA1c value at end of the comparative period (LOCF) lower than HbA1c baseline value AND \* HbA1c value at end of the comparative period (LOCF) ≥7% |
| Body Weight: Change From Baseline to the End of the Comparative Period | baseline (week 0), week 2, week 6, week 12, week 18, week 24 | Change = Last weight value measured during the comparative period (LOCF value) - weight value at baseline |
| Body Weight: Change From Beginning to End of the Extension Period | week 24, week 30, week 36, week 48 | Change = Last weight value measured during the extension period (LOCF value) - weight value at beginning of the Extension Period (Week 24) |
| Daily Dose of Insulin Glargine | week 1, week 2, week 6, week 12, week 24 | — |
| Daily Dose of Liraglutide | week 1, week 2, week 6, week 12, week 24 | — |
| Daily Dose of Insulin Glargine Administered During the Extension Period | week 30, week 36, week 48 | — |
| Hypoglycemia Occurence: Number of Patients With at Least One Episode of Symptomatic / Severe Symptomatic Hypoglycemia During the Comparative Period | all across the comparative period (from week 0 to week 24) | Symptomatic hypoglycemia was defined as an event with clinical symptoms that were considered to result from hypoglycemia. Severe symptomatic hypoglycemia was defined as an event with clinical symptoms that were considered to result from hypoglycemia, requiring the assistance of another person for active administration of carbohydrate, glucagon or other countermeasure because the patient could not treat him/herself due to acute neurological impairment directly resulting from the hypoglycemia (assistance by another person when the patient could have treated him/herself was not considered as requiring assistance)and one of the following criteria: * The event was associated with a measured PG level \< 36 mg/dL (2 mmol/L), * Or, in absence of PG value, the event was associated with neurological recovery attributable to the restoration of PG to normal, after oral carbohydrate, intravenous glucose or glucagon administration. |
| Hypoglycemia Occurence: Number of Patients With at Least One Episode of Symptomatic / Severe Symptomatic Hypoglycemia During the Extension Period | all across the extension period (from week 24 to week 48) | Symptomatic hypoglycemia was defined as an event with clinical symptoms that were considered to result from hypoglycemia. Severe symptomatic hypoglycemia was defined as an event with clinical symptoms that were considered to result from hypoglycemia, requiring the assistance of another person for active administration of carbohydrate, glucagon or other countermeasure because the patient could not treat him/herself due to acute neurological impairment directly resulting from the hypoglycemia (assistance by another person when the patient could have treated him/herself was not considered as requiring assistance)and one of the following criteria: * The event was associated with a measured PG level \< 36 mg/dL (2 mmol/L), * Or, in absence of PG value, the event was associated with neurological recovery attributable to the restoration of PG to normal, after oral carbohydrate, intravenous glucose or glucagon administration. |
| Self-Monitored 7-point Plasma Glucose (PG) Profile: Change From Beginning to the End of the Extension Period | week 24, week 36, week 48 | Self-monitored 7-point plasma glucose profiles (before and 2 hours after the start of breakfast, lunch and dinner, and at bedtime) recorded on 3 consecutive days in the week before each visit Value at the end of the extension period defined as last available value during the extension period (i.e. last-observation-carried-forward \[LOCF\] value) Change = LOCF value - week 24 value |
Countries
Austria, Brazil, Canada, Czechia, Finland, France, Greece, Ireland, Israel, Mexico, Netherlands, Russia, Slovakia, Spain, Sweden, Turkey (Türkiye), United States
Participant flow
Recruitment details
The first patient was enrolled on July 23, 2010. The 24-week comparative period was completed on October 5, 2012. The extension period was initiated on March 24, 2011 and completed on March 6, 2013.
Pre-assignment details
A total of 1456 patients were screened in 136 centers, in 17 countries (Austria, Brazil, Canada, Czech Republic, Finland, France, Greece, Ireland, Israel, Mexico, Netherlands, Russian Federation Slovakia, Spain, Sweden, Turkey, USA). Among them, 478 (32.8%) patients were not randomized (main reason was Glycosylated Haemoglobin A1c out of range).
Participants by arm
| Arm | Count |
|---|---|
| Insulin Glargine Insulin glargine starting dose: 0.2 Unit per kilogram of body weight or 10 Units. Insulin titration (by 2 or 4 Units) every 3 days according to the median value of Fast Plasma Glucose of the last 3 days. | 474 |
| Liraglutide Liraglutide dose: 0.6 mg/day during the first week, 1.2 mg/day during the second week and 1.8 mg/day until week 24. | 470 |
| Total | 944 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Comparative Period | Adverse Event | 6 | 33 |
| Comparative Period | Lack of Efficacy | 1 | 0 |
| Comparative Period | Lost to Follow-up | 11 | 7 |
| Comparative Period | Move to another city/country | 2 | 1 |
| Comparative Period | Not Treated | 5 | 8 |
| Comparative Period | Physician Decision | 0 | 1 |
| Comparative Period | Protocol Violation | 8 | 12 |
| Comparative Period | Withdrawal by Subject | 9 | 13 |
| Extension Period | Adverse Event | 0 | 2 |
| Extension Period | Inclusion criteria not respected | 0 | 1 |
| Extension Period | Lack of Efficacy | 0 | 2 |
| Extension Period | Lost to Follow-up | 0 | 2 |
| Extension Period | Not included in extension, not treated | 0 | 50 |
| Extension Period | Prohibited medication | 0 | 1 |
| Extension Period | Protocol Violation | 0 | 2 |
| Extension Period | Withdrawal by Subject | 0 | 3 |
Baseline characteristics
| Characteristic | Insulin Glargine | Liraglutide | Total |
|---|---|---|---|
| Age, Continuous | 57.07 years STANDARD_DEVIATION 8.78 | 57.44 years STANDARD_DEVIATION 8.85 | 57.25 years STANDARD_DEVIATION 8.81 |
| At least one diabetic late complication No | 262 participants | 247 participants | 509 participants |
| At least one diabetic late complication Yes | 212 participants | 223 participants | 435 participants |
| Body Mass Index (BMI) at week -2 | 32.00 kg/m² STANDARD_DEVIATION 4.24 | 31.75 kg/m² STANDARD_DEVIATION 4.12 | 31.88 kg/m² STANDARD_DEVIATION 4.18 |
| Duration of Type 2 diabetes | 8.54 years | 8.41 years | 8.49 years |
| Glycosylated Hemoglobin A1c (HbA1c) at week -2 | 9.04 percent STANDARD_DEVIATION 1.1 | 9.11 percent STANDARD_DEVIATION 1.09 | 9.07 percent STANDARD_DEVIATION 1.09 |
| Sex: Female, Male Female | 224 Participants | 207 Participants | 431 Participants |
| Sex: Female, Male Male | 250 Participants | 263 Participants | 513 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — |
| other Total, other adverse events | 92 / 484 | 239 / 481 | 22 / 160 |
| serious Total, serious adverse events | 11 / 484 | 15 / 481 | 5 / 160 |
Outcome results
Primary
Percentage of Patients Whose Glycosylated Haemoglobin (HbA1c) <7% at the End of the Comparative Period
The value at the end of the comparative period was defined as the last available HbA1c value measured during the comparative period plus 14 days after the last dose of Investigational Product (i.e. last-observation-carried-forward \[LOCF\] value).
Time frame: week 12, week 24
Population: The population analyzed for this outcome measure consisted of the subset of mITT patients who had at least one HbA1c value on treatment during the comparative period.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Insulin Glargine | Percentage of Patients Whose Glycosylated Haemoglobin (HbA1c) <7% at the End of the Comparative Period | 48.4 percentage of participants |
| Liraglutide | Percentage of Patients Whose Glycosylated Haemoglobin (HbA1c) <7% at the End of the Comparative Period | 45.9 percentage of participants |
Comparison: Superiority testing~H0: Rate measured with insulin glargine = rate measured with liraglutide~H1: Rate measured with insulin glargine ≠ rate measured with liraglutide~Sample size calculation (465 randomized patients per arm) was based on the assumption of an expected success rate of 46% with insulin glargine and 35% with liraglutide, an alpha risk of 5% (2-sided) and a power of 90%, taking into account an estimated non evaluability rate of 10%.p-value: 0.43995% CI: [-3.88, 8.93]Chi-squared
Secondary
Body Weight: Change From Baseline to the End of the Comparative Period
Change = Last weight value measured during the comparative period (LOCF value) - weight value at baseline
Time frame: baseline (week 0), week 2, week 6, week 12, week 18, week 24
Population: The population analyzed for this outcome measure consisted of the subset of mITT patients who had at least one weight value on treatment during the comparative period.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Insulin Glargine | Body Weight: Change From Baseline to the End of the Comparative Period | 1.98 kg | Standard Deviation 3.95 |
| Liraglutide | Body Weight: Change From Baseline to the End of the Comparative Period | -2.99 kg | Standard Deviation 3.64 |
Secondary
Body Weight: Change From Beginning to End of the Extension Period
Change = Last weight value measured during the extension period (LOCF value) - weight value at beginning of the Extension Period (Week 24)
Time frame: week 24, week 30, week 36, week 48
Population: The population analyzed for this outcome measure consisted of the mITT population (extension).
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Insulin Glargine | Body Weight: Change From Beginning to End of the Extension Period | 4.35 kg | Standard Deviation 3.39 |
Secondary
Daily Dose of Insulin Glargine
Time frame: week 1, week 2, week 6, week 12, week 24
Population: The population considered was the mITT population but due to missing values, different subsets of this mITT population were analyzed at each week.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Insulin Glargine | Daily Dose of Insulin Glargine | Start of treatment (N=472) | 13.39 Unit (U) | Standard Deviation 4.87 |
| Insulin Glargine | Daily Dose of Insulin Glargine | Week 1 (N=470) | 17.74 Unit (U) | Standard Deviation 6.52 |
| Insulin Glargine | Daily Dose of Insulin Glargine | Week 2 (N=470) | 22.06 Unit (U) | Standard Deviation 8.4 |
| Insulin Glargine | Daily Dose of Insulin Glargine | Week 6 (N=470) | 34.67 Unit (U) | Standard Deviation 17.03 |
| Insulin Glargine | Daily Dose of Insulin Glargine | Week 12 (N=463) | 44.40 Unit (U) | Standard Deviation 26.63 |
| Insulin Glargine | Daily Dose of Insulin Glargine | Week 18 (N=454) | 48.65 Unit (U) | Standard Deviation 31.03 |
| Insulin Glargine | Daily Dose of Insulin Glargine | Week 24 (N=459) | 51.67 Unit (U) | Standard Deviation 34.05 |
| Insulin Glargine | Daily Dose of Insulin Glargine | End comparative period (LOCF) (N=474) | 51.24 Unit (U) | Standard Deviation 33.93 |
Secondary
Daily Dose of Insulin Glargine Administered During the Extension Period
Time frame: week 30, week 36, week 48
Population: The population considered was the mITT population (extension) but due to missing values, different subsets of this mITT population were analyzed at each week.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Insulin Glargine | Daily Dose of Insulin Glargine Administered During the Extension Period | Start of treatment (N=154) | 15.77 Unit (U) | Standard Deviation 4.53 |
| Insulin Glargine | Daily Dose of Insulin Glargine Administered During the Extension Period | Week 30 (N=151) | 37.49 Unit (U) | Standard Deviation 15.7 |
| Insulin Glargine | Daily Dose of Insulin Glargine Administered During the Extension Period | Week 36 (N=150) | 46.21 Unit (U) | Standard Deviation 23.06 |
| Insulin Glargine | Daily Dose of Insulin Glargine Administered During the Extension Period | Week 48 (N=151) | 50.68 Unit (U) | Standard Deviation 27.33 |
Secondary
Daily Dose of Liraglutide
Time frame: week 1, week 2, week 6, week 12, week 24
Population: The population considered was the mITT population but due to missing values, different subsets of this mITT population were analyzed at each week.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Insulin Glargine | Daily Dose of Liraglutide | Start of treatment (N=470) | 0.60 mg | Standard Deviation 0 |
| Insulin Glargine | Daily Dose of Liraglutide | Week 1 (N=463) | 0.91 mg | Standard Deviation 0.31 |
| Insulin Glargine | Daily Dose of Liraglutide | Week 2 (N=458) | 1.49 mg | Standard Deviation 0.33 |
| Insulin Glargine | Daily Dose of Liraglutide | Week 6 (N=444) | 1.72 mg | Standard Deviation 0.21 |
| Insulin Glargine | Daily Dose of Liraglutide | Week 12 (N=426) | 1.73 mg | Standard Deviation 0.19 |
| Insulin Glargine | Daily Dose of Liraglutide | Week 18 (N=415) | 1.74 mg | Standard Deviation 0.18 |
| Insulin Glargine | Daily Dose of Liraglutide | Week 24 (N=431) | 1.73 mg | Standard Deviation 0.21 |
| Insulin Glargine | Daily Dose of Liraglutide | End comparative period (LOCF) (N=470) | 1.71 mg | Standard Deviation 0.24 |
Secondary
Glycosylated Haemoglobin (HbA1c): Change From Baseline to the End of Comparative Period
Change in HbA1C from baseline to the last observation carried forward (LOCF) measured during the comparative period = LOCF value - baseline value
Time frame: baseline (week -2), week 12, week 24
Population: The population analyzed for this outcome measure consisted of the subset of mITT patients who had at least one HbA1c value on treatment during the comparative period.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Insulin Glargine | Glycosylated Haemoglobin (HbA1c): Change From Baseline to the End of Comparative Period | -1.92 percent | Standard Deviation 1.22 |
| Liraglutide | Glycosylated Haemoglobin (HbA1c): Change From Baseline to the End of Comparative Period | -1.81 percent | Standard Deviation 1.33 |
Secondary
Glycosylated Haemoglobin (HbA1c): Change From Beginning to the End of the Extension Period
Change in HbA1C from beginning of the extension period (week 24) to the last observation carried forward (LOCF) measured during the extension period = LOCF value - week 24 value
Time frame: week 24, week 36, week 48
Population: The population analyzed for this outcome measure consisted of the subset of mITT population (extension) who had HbA1c value both at beginning of the extension and at least one value on treatment during the extension period.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Insulin Glargine | Glycosylated Haemoglobin (HbA1c): Change From Beginning to the End of the Extension Period | -0.26 percent | Standard Deviation 1.11 |
Secondary
Hypoglycemia Occurence: Number of Patients With at Least One Episode of Symptomatic / Severe Symptomatic Hypoglycemia During the Comparative Period
Symptomatic hypoglycemia was defined as an event with clinical symptoms that were considered to result from hypoglycemia. Severe symptomatic hypoglycemia was defined as an event with clinical symptoms that were considered to result from hypoglycemia, requiring the assistance of another person for active administration of carbohydrate, glucagon or other countermeasure because the patient could not treat him/herself due to acute neurological impairment directly resulting from the hypoglycemia (assistance by another person when the patient could have treated him/herself was not considered as requiring assistance)and one of the following criteria: * The event was associated with a measured PG level \< 36 mg/dL (2 mmol/L), * Or, in absence of PG value, the event was associated with neurological recovery attributable to the restoration of PG to normal, after oral carbohydrate, intravenous glucose or glucagon administration.
Time frame: all across the comparative period (from week 0 to week 24)
Population: The population analyzed was the safety population i.e. all randomized and treated patients.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Insulin Glargine | Hypoglycemia Occurence: Number of Patients With at Least One Episode of Symptomatic / Severe Symptomatic Hypoglycemia During the Comparative Period | symptomatic hypoglycemia | 219 participants |
| Insulin Glargine | Hypoglycemia Occurence: Number of Patients With at Least One Episode of Symptomatic / Severe Symptomatic Hypoglycemia During the Comparative Period | severe symptomatic hypoglycemia | 0 participants |
| Liraglutide | Hypoglycemia Occurence: Number of Patients With at Least One Episode of Symptomatic / Severe Symptomatic Hypoglycemia During the Comparative Period | symptomatic hypoglycemia | 85 participants |
| Liraglutide | Hypoglycemia Occurence: Number of Patients With at Least One Episode of Symptomatic / Severe Symptomatic Hypoglycemia During the Comparative Period | severe symptomatic hypoglycemia | 2 participants |
Secondary
Hypoglycemia Occurence: Number of Patients With at Least One Episode of Symptomatic / Severe Symptomatic Hypoglycemia During the Extension Period
Symptomatic hypoglycemia was defined as an event with clinical symptoms that were considered to result from hypoglycemia. Severe symptomatic hypoglycemia was defined as an event with clinical symptoms that were considered to result from hypoglycemia, requiring the assistance of another person for active administration of carbohydrate, glucagon or other countermeasure because the patient could not treat him/herself due to acute neurological impairment directly resulting from the hypoglycemia (assistance by another person when the patient could have treated him/herself was not considered as requiring assistance)and one of the following criteria: * The event was associated with a measured PG level \< 36 mg/dL (2 mmol/L), * Or, in absence of PG value, the event was associated with neurological recovery attributable to the restoration of PG to normal, after oral carbohydrate, intravenous glucose or glucagon administration.
Time frame: all across the extension period (from week 24 to week 48)
Population: The population analyzed was the safety population (extension) i.e. all treated patients during the extension period.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Insulin Glargine | Hypoglycemia Occurence: Number of Patients With at Least One Episode of Symptomatic / Severe Symptomatic Hypoglycemia During the Extension Period | symptomatic hypoglycemia | 58 participants |
| Insulin Glargine | Hypoglycemia Occurence: Number of Patients With at Least One Episode of Symptomatic / Severe Symptomatic Hypoglycemia During the Extension Period | severe symptomatic hypoglycemia | 0 participants |
Secondary
Percentage of Patients Whose Glycosylated Haemoglobin (HbA1c) <7% at the End of the Extension Period
Value at the end of the extension period defined as last available HbA1c value measured during the extension period (i.e. last observation carried forward (LOCF) value)
Time frame: week 36, week 48
Population: The population analyzed for this outcome measure consisted of the mITT patients who had at least one HbA1c value on treatment during the extension period.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Insulin Glargine | Percentage of Patients Whose Glycosylated Haemoglobin (HbA1c) <7% at the End of the Extension Period | 22.7 percentage of participants |
Secondary
Percentage of Patients Whose Glycosylated Haemoglobin (HbA1c) Has Decreased But Remains ≥7% at the End of the Comparative Period
Percentage of patients with: \* HbA1c value at end of the comparative period (LOCF) lower than HbA1c baseline value AND \* HbA1c value at end of the comparative period (LOCF) ≥7%
Time frame: baseline (week -2), week 12, week 24
Population: The population analyzed for this outcome measure consisted of the subset of mITT patients who had at least one HbA1c value on treatment during the comparative period.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Insulin Glargine | Percentage of Patients Whose Glycosylated Haemoglobin (HbA1c) Has Decreased But Remains ≥7% at the End of the Comparative Period | 47.1 percentage of participants |
| Liraglutide | Percentage of Patients Whose Glycosylated Haemoglobin (HbA1c) Has Decreased But Remains ≥7% at the End of the Comparative Period | 46.3 percentage of participants |
Secondary
Percentage of Patients Whose Glycosylated Haemoglobin (HbA1c) Has Increased at the End of the Comparative Period
Percentage of patients with HbA1c value at end of the comparative period (LOCF) higher than HbA1c baseline value
Time frame: baseline (week -2), week 12, week 24
Population: The population analyzed for this outcome measure consisted of the subset of mITT patients who had at least one HbA1c value on treatment during the comparative period.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Insulin Glargine | Percentage of Patients Whose Glycosylated Haemoglobin (HbA1c) Has Increased at the End of the Comparative Period | 4.1 percentage of participants |
| Liraglutide | Percentage of Patients Whose Glycosylated Haemoglobin (HbA1c) Has Increased at the End of the Comparative Period | 6.6 percentage of participants |
Secondary
Self-Monitored 7-point Plasma Glucose (PG) Profile: Change From Baseline to the End of the Comparative Period
Self-monitored 7-point plasma glucose profiles (before and 2 hours after the start of breakfast, lunch and dinner, and at bedtime) recorded on 3 consecutive days in the week before each visit Value at the end of the comparative period defined as last available value during the comparative period (i.e. last-observation-carried-forward \[LOCF\] value) Change = LOCF value - baseline value
Time frame: baseline (week 0), week 12, week 24
Population: The population considered was the mITT population but due to missing values, different subsets of this mITT population were analyzed for each time point of the profile.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Insulin Glargine | Self-Monitored 7-point Plasma Glucose (PG) Profile: Change From Baseline to the End of the Comparative Period | Before lunch (N ig = 438 & N l = 404) | -50.16 mg/dL | Standard Deviation 59.53 |
| Insulin Glargine | Self-Monitored 7-point Plasma Glucose (PG) Profile: Change From Baseline to the End of the Comparative Period | Before dinner (N ig = 434 & N l = 400) | -40.84 mg/dL | Standard Deviation 58.88 |
| Insulin Glargine | Self-Monitored 7-point Plasma Glucose (PG) Profile: Change From Baseline to the End of the Comparative Period | After breakfast (N ig = 440 & N l = 397) | -66.70 mg/dL | Standard Deviation 63.29 |
| Insulin Glargine | Self-Monitored 7-point Plasma Glucose (PG) Profile: Change From Baseline to the End of the Comparative Period | After dinner (N ig = 426 & N l = 396) | -42.6 mg/dL | Standard Deviation 61.74 |
| Insulin Glargine | Self-Monitored 7-point Plasma Glucose (PG) Profile: Change From Baseline to the End of the Comparative Period | After lunch (N ig = 433 & N l = 406) | -43.00 mg/dL | Standard Deviation 58.42 |
| Insulin Glargine | Self-Monitored 7-point Plasma Glucose (PG) Profile: Change From Baseline to the End of the Comparative Period | At bedtime (N ig = 380 & N l = 351) | -43.11 mg/dL | Standard Deviation 60.37 |
| Insulin Glargine | Self-Monitored 7-point Plasma Glucose (PG) Profile: Change From Baseline to the End of the Comparative Period | Before breakfast (N ig = 448 & N l = 409) | -65.92 mg/dL | Standard Deviation 50.29 |
| Liraglutide | Self-Monitored 7-point Plasma Glucose (PG) Profile: Change From Baseline to the End of the Comparative Period | At bedtime (N ig = 380 & N l = 351) | -44.06 mg/dL | Standard Deviation 59.8 |
| Liraglutide | Self-Monitored 7-point Plasma Glucose (PG) Profile: Change From Baseline to the End of the Comparative Period | Before breakfast (N ig = 448 & N l = 409) | -38.64 mg/dL | Standard Deviation 46.17 |
| Liraglutide | Self-Monitored 7-point Plasma Glucose (PG) Profile: Change From Baseline to the End of the Comparative Period | After breakfast (N ig = 440 & N l = 397) | -55.35 mg/dL | Standard Deviation 61.56 |
| Liraglutide | Self-Monitored 7-point Plasma Glucose (PG) Profile: Change From Baseline to the End of the Comparative Period | Before lunch (N ig = 438 & N l = 404) | -39.13 mg/dL | Standard Deviation 58.78 |
| Liraglutide | Self-Monitored 7-point Plasma Glucose (PG) Profile: Change From Baseline to the End of the Comparative Period | After lunch (N ig = 433 & N l = 406) | -41.82 mg/dL | Standard Deviation 61.16 |
| Liraglutide | Self-Monitored 7-point Plasma Glucose (PG) Profile: Change From Baseline to the End of the Comparative Period | Before dinner (N ig = 434 & N l = 400) | -36.88 mg/dL | Standard Deviation 58.49 |
| Liraglutide | Self-Monitored 7-point Plasma Glucose (PG) Profile: Change From Baseline to the End of the Comparative Period | After dinner (N ig = 426 & N l = 396) | -45.04 mg/dL | Standard Deviation 60.42 |
Secondary
Self-Monitored 7-point Plasma Glucose (PG) Profile: Change From Beginning to the End of the Extension Period
Self-monitored 7-point plasma glucose profiles (before and 2 hours after the start of breakfast, lunch and dinner, and at bedtime) recorded on 3 consecutive days in the week before each visit Value at the end of the extension period defined as last available value during the extension period (i.e. last-observation-carried-forward \[LOCF\] value) Change = LOCF value - week 24 value
Time frame: week 24, week 36, week 48
Population: The population considered was the mITT population (extension) but due to missing values, different subsets of this population were analyzed for each time point of the profile.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Insulin Glargine | Self-Monitored 7-point Plasma Glucose (PG) Profile: Change From Beginning to the End of the Extension Period | Before dinner (N=133) | -12.56 mg/dL | Standard Deviation 54.57 |
| Insulin Glargine | Self-Monitored 7-point Plasma Glucose (PG) Profile: Change From Beginning to the End of the Extension Period | Before breakfast (N=143) | -46.13 mg/dL | Standard Deviation 44.89 |
| Insulin Glargine | Self-Monitored 7-point Plasma Glucose (PG) Profile: Change From Beginning to the End of the Extension Period | After breakfast (N=134) | -27.67 mg/dL | Standard Deviation 52.37 |
| Insulin Glargine | Self-Monitored 7-point Plasma Glucose (PG) Profile: Change From Beginning to the End of the Extension Period | Before lunch (N=131) | -20.32 mg/dL | Standard Deviation 57.58 |
| Insulin Glargine | Self-Monitored 7-point Plasma Glucose (PG) Profile: Change From Beginning to the End of the Extension Period | After lunch (N=134) | -11.50 mg/dL | Standard Deviation 58.37 |
| Insulin Glargine | Self-Monitored 7-point Plasma Glucose (PG) Profile: Change From Beginning to the End of the Extension Period | After dinner (N=130) | -2.28 mg/dL | Standard Deviation 54.55 |
| Insulin Glargine | Self-Monitored 7-point Plasma Glucose (PG) Profile: Change From Beginning to the End of the Extension Period | At bedtime (N=127) | -14.94 mg/dL | Standard Deviation 52.67 |
Secondary
Self-Monitored Fasting Plasma Glucose (SMFPG) Measurements: Change From Baseline to the End of the Comparative Period
SMFPG = mean value of Self-Monitored Fasting Plasma Glucose measurements over 3 consecutive days in the week before each visit Value at the end of the comparative period defined as last available value during the comparative period (i.e. last-observation-carried-forward \[LOCF\] value) Change = LOCF value - baseline value
Time frame: baseline (week 0), week 6, week 12, week 18, week 24
Population: The population analyzed for this outcome measure consisted of the subset of mITT patients who had at least one SMFPG value on treatment during the comparative period.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Insulin Glargine | Self-Monitored Fasting Plasma Glucose (SMFPG) Measurements: Change From Baseline to the End of the Comparative Period | -65.25 mg/dL | Standard Deviation 50.95 |
| Liraglutide | Self-Monitored Fasting Plasma Glucose (SMFPG) Measurements: Change From Baseline to the End of the Comparative Period | -37.23 mg/dL | Standard Deviation 47.31 |
Secondary
Self-Monitored Fasting Plasma Glucose (SMFPG) Measurements: Change From Beginning to the End of the Extension Period
SMFPG = mean value of Self-Monitored Fasting Plasma Glucose measurements over 3 consecutive days in the week before each visit Value at the end of the extension period defined as last available value during the extension period (i.e. last-observation-carried-forward \[LOCF\] value) Change = LOCF value - week 24 value
Time frame: week 24, week 30, week 36, week 48
Population: The population analyzed for this outcome measure consisted of the subset of mITT (extension) patients who had SMFPG value both at beginning of the extension and at least one value on treatment during the extension period.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Insulin Glargine | Self-Monitored Fasting Plasma Glucose (SMFPG) Measurements: Change From Beginning to the End of the Extension Period | -44.63 mg/dL | Standard Deviation 45.47 |