Efficacy Assessment of Insulin Glargine Versus LiraglutidE After Oral Agents Failure

Phase 4

Completed

Conditions: Diabetes Mellitus, Type 2

Interventions: Drug: Liraglutide
Drug: Insulin glargine
Drug: Metformin

Registration Number: NCT01117350

Lead Sponsor: Sanofi

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

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 978

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Liraglutide	Liraglutide	Liraglutide administered once a day, in the morning or in the evening, at the most convenient time. The time of injection , once chosen was to remain unchanged during the whole duration of the study. The dose was 0.6 mg/day during the first week, 1.2 mg/day during the second week and 1.8 mg/day until week 24. The dose might be decreased to 1.2 mg for safety reasons (e.g. gastro-intestinal tolerability), based on Investigator's judgment.
Insulin Glargine	Insulin glargine	Insulin glargine administered once a day, in the morning or in the evening, at the most convenient time. The time of injection, once chosen was to remain unchanged during the whole duration of the study. The starting dose was 0.2 Unit per kilogram of body weight or 10 Units. Patients were empowered to adjust their insulin doses, under strict investigator's supervision. Insulin titration (by 2 or 4 Units) was done every 3 days according to the median value of Fasting Plasma Glucose (FPG) of the last 3 days. The goal was to achieve 70 \< FPG ≤ 100 mg/dL (3.9 \< FPG ≤ 5.5 mmol/L). Minor deviations from the titration scheme could be allowed, based on Investigator's judgment and patient's situation.
Insulin Glargine	Metformin	Insulin glargine administered once a day, in the morning or in the evening, at the most convenient time. The time of injection, once chosen was to remain unchanged during the whole duration of the study. The starting dose was 0.2 Unit per kilogram of body weight or 10 Units. Patients were empowered to adjust their insulin doses, under strict investigator's supervision. Insulin titration (by 2 or 4 Units) was done every 3 days according to the median value of Fasting Plasma Glucose (FPG) of the last 3 days. The goal was to achieve 70 \< FPG ≤ 100 mg/dL (3.9 \< FPG ≤ 5.5 mmol/L). Minor deviations from the titration scheme could be allowed, based on Investigator's judgment and patient's situation.
Liraglutide	Metformin	Liraglutide administered once a day, in the morning or in the evening, at the most convenient time. The time of injection , once chosen was to remain unchanged during the whole duration of the study. The dose was 0.6 mg/day during the first week, 1.2 mg/day during the second week and 1.8 mg/day until week 24. The dose might be decreased to 1.2 mg for safety reasons (e.g. gastro-intestinal tolerability), based on Investigator's judgment.

Primary Outcome Measures

Name	Time	Method
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 Outcome Measures

Name	Time	Method
Daily Dose of Insulin Glargine	week 1, week 2, week 6, week 12, week 24
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%
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
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)
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
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
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
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 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.

Trial Locations

Locations (136): Investigational Site Number 840023
🇺🇸
Birmingham, Alabama, United States
Investigational Site Number 840002
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Goodyear, Arizona, United States
Investigational Site Number 840047
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Phoenix, Arizona, United States
Investigational Site Number 840017
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La Jolla, California, United States
Investigational Site Number 840036
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La Mesa, California, United States
Investigational Site Number 840037
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Loma Linda, California, United States
Investigational Site Number 840045
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Long Beach, California, United States
Investigational Site Number 840048
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Mission Hills, California, United States
Investigational Site Number 840033
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Mission Viejo, California, United States
Investigational Site Number 840019
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Palm Springs, California, United States
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Investigational Site Number 840023
🇺🇸Birmingham, Alabama, United States