Efficacy Assessment of Insulin Glargine Versus LiraglutidE After Oral Agents Failure

NCT01117350 | Completed Phase 4 Results

• 3 other identifiers: LANTU_C_036802010-018437-21U1111-1116-9684
• Study Type: interventional
• Target: 978
• Locations: 17 countries
• Sites: 136

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

Conditions

Diabetes Mellitus, Type 2

Outcome Measures

Primary Outcomes (1)

• 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).

  week 12, week 24

Secondary Outcomes (16)

• 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 Whose Glycosylated Haemoglobin (HbA1c) Has Increased at the End of the Comparative Period

  baseline (week -2), week 12, week 24

• Glycosylated Haemoglobin (HbA1c): Change From Baseline to the End of Comparative Period

  baseline (week -2), week 12, week 24

• Glycosylated Haemoglobin (HbA1c): Change From Beginning to the End of the Extension Period

  week 24, week 36, week 48

• Percentage of Patients Whose Glycosylated Haemoglobin (HbA1c) <7% at the End of the Extension Period

  week 36, week 48

Study Arms (2)

Insulin Glargine

EXPERIMENTAL

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.

Drug: Insulin glargine; Drug: Metformin

Liraglutide

ACTIVE COMPARATOR

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.

Drug: Liraglutide; Drug: Metformin

Interventions

Insulin glargine DRUG

100 Units/mL solution for injection in a pre-filled SoloStar pen

Also known as: Lantus®

Insulin Glargine

Liraglutide DRUG

6 mg/mL solution for injection in a 3-mL pre-filled pen (18mg)

Also known as: Victoza®

Liraglutide

Metformin DRUG

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.

Insulin Glargine; Liraglutide

Eligibility Criteria

• Age: 35 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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,
• % \< 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.
• 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)

You may not qualify if:

• 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,

Sponsors & Collaborators

• Sanofi: lead

Study Sites (136)

Investigational Site Number 840023

Birmingham, Alabama, 35294, United States

Location

Investigational Site Number 840002

Goodyear, Arizona, 85395, United States

Location

Investigational Site Number 840047

Phoenix, Arizona, 85020, United States

Location

Investigational Site Number 840017

La Jolla, California, 92037, United States

Location

Investigational Site Number 840036

La Mesa, California, 91942, United States

Location

Investigational Site Number 840037

Loma Linda, California, 92357, United States

Location

Investigational Site Number 840045

Long Beach, California, 90822, United States

Location

Investigational Site Number 840048

Mission Hills, California, 91345, United States

Location

Investigational Site Number 840033

Mission Viejo, California, 92691, United States

Location

Investigational Site Number 840019

Palm Springs, California, 92262, United States

Location

Investigational Site Number 840039

San Diego, California, 92101, United States

Location

Investigational Site Number 840042

San Diego, California, 92161, United States

Location

Investigational Site Number 840043

Tustin, California, 92780, United States

Location

Investigational Site Number 840028

Denver, Colorado, 80220, United States

Location

Investigational Site Number 840034

Grand Junction, Colorado, 81501, United States

Location

Investigational Site Number 840026

Longmont, Colorado, 80501, United States

Location

Investigational Site Number 840022

Lawrenceville, Georgia, United States

Location

Investigational Site Number 840029

Roswell, Georgia, 30076, United States

Location

Investigational Site Number 840009

Arlington Heights, Illinois, 60004, United States

Location

Investigational Site Number 840051

Springfield, Illinois, 62704, United States

Location

Investigational Site Number 840050

Indianapolis, Indiana, 46222, United States

Location

Investigational Site Number 840031

Kansas City, Kansas, 66160, United States

Location

Investigational Site Number 840004

Paducah, Kentucky, 42003, United States

Location

Investigational Site Number 840010

Rockville, Maryland, 20850, United States

Location

Investigational Site Number 840038

Eagan, Minnesota, 55122, United States

Location

Investigational Site Number 840030

Minneapolis, Minnesota, 55414, United States

Location

Investigational Site Number 840012

St Louis, Missouri, 63128, United States

Location

Investigational Site Number 840044

St Louis, Missouri, 63141, United States

Location

Investigational Site Number 840015

Atco, New Jersey, 08004, United States

Location

Investigational Site Number 840008

Blackwood, New Jersey, 08012, United States

Location

Investigational Site Number 840027

Mineola, New York, 11501, United States

Location

Investigational Site Number 840011

Staten Island, New York, 10301-3914, United States

Location

Investigational Site Number 840005

Hickory, North Carolina, 28601, United States

Location

Investigational Site Number 840052

Winston-Salem, North Carolina, 27103, United States

Location

Investigational Site Number 840049

Fargo, North Dakota, 58103, United States

Location

Investigational Site Number 840006

Bryan, Ohio, 43506, United States

Location

Investigational Site Number 840035

Cincinnati, Ohio, 45220, United States

Location

Investigational Site Number 840016

Carnegie, Pennsylvania, 15106, United States

Location

Investigational Site Number 840020

Uniontown, Pennsylvania, 15401, United States

Location

Investigational Site Number 840024

Rapid City, South Dakota, 57701, United States

Location

Investigational Site Number 840001

Dallas, Texas, 75230, United States

Location

Investigational Site Number 840007

Dallas, Texas, 75246, United States

Location

Investigational Site Number 840013

Houston, Texas, 77030, United States

Location

Investigational Site Number 840014

Renton, Washington, 98057, United States

Location

Investigational Site Number 840046

Spokane, Washington, 99220-3649, United States

Location

Investigational Site Number 040-006

Salzburg, 5010, Austria

Location

Investigational Site Number 040-007

Salzburg, 5020, Austria

Location

Investigational Site Number 040-003

Stockerau, A-2000, Austria

Location

Investigational Site Number 040-005

Vienna, A-1010, Austria

Location

Investigational Site Number 040-002

Vienna, A-1090, Austria

Location

Investigational Site Number 040-001

Vienna, A-1130, Austria

Location

Investigational Site Number 040-004

Vienna, A-1220, Austria

Location

Investigational Site Number 076-004

Belém, 66073-000, Brazil

Location

Investigational Site Number 076-007

Fortaleza, 60015-052, Brazil

Location

Investigational Site Number 076-001

Fortaleza, 60115-282, Brazil

Location

Investigational Site Number 076-006

Fortaleza, 60430-370, Brazil

Location

Investigational Site Number 076-005

Marília, 17519-101, Brazil

Location

Investigational Site Number 076-002

São Paulo, 01244-030, Brazil

Location

Investigational Site Number 124-003

Mississauga, L5M2V8, Canada

Location

Investigational Site Number 124-001

Montreal, H2W1T8, Canada

Location

Investigational Site Number 124-006

Montreal, H3A1A1, Canada

Location

Investigational Site Number 124-004

Toronto, M5C 2T2, Canada

Location

Investigational Site Number 124-008

Vancouver, V5Z1M9, Canada

Location

Investigational Site Number 124-007

Victoria, V8R1J8, Canada

Location

Investigational Site Number 203001

Hradec Králové, 50005, Czechia

Location

Investigational Site Number 203003

Krnov, 79401, Czechia

Location

Investigational Site Number 203005

Kroměříž, 76701, Czechia

Location

Investigational Site Number 203002

Olomouc, 77900, Czechia

Location

Investigational Site Number 203006

Prague, 15000, Czechia

Location

Investigational Site Number 246003

Harjavalta, 29200, Finland

Location

Investigational Site Number 246001

Kuopio, 70210, Finland

Location

Investigational Site Number 246002

Oulu, 90100, Finland

Location

Investigational Site Number 246004

Turku, 20100, Finland

Location

Investigational Site Number 250-007

Annecy, 74000, France

Location

Investigational Site Number 250-017

Bois-Guillaume, 76233, France

Location

Investigational Site Number 250-003

Boulogne-Billancourt, 92100, France

Location

Investigational Site Number 250-011

Brest, 29000, France

Location

Investigational Site Number 250-008

Cahors, 46005, France

Location

Investigational Site Number 250-012

Corbeil-Essonnes, 91100, France

Location

Investigational Site Number 250-009

La Rochelle, 17019, France

Location

Investigational Site Number 250-004

Le Creusot, 71200, France

Location

Investigational Site Number 250-006

Mantes-la-Jolie, 78200, France

Location

Investigational Site Number 250-021

Nanterre, 92014, France

Location

Investigational Site Number 250022

Strasbourg, 67000, France

Location

Investigational Site Number 250-020

Strasbourg, 67091, France

Location

Investigational Site Number 250-002

Toulouse, 31300, France

Location

Investigational Site Number 250-016

Vénissieux, 69200, France

Location

Investigational Site Number 300003

Athens, Greece

Location

Investigational Site Number 300004

Athens, Greece

Location

Investigational Site Number 300001

Haidari, Athens, 12462, Greece

Location

Investigational Site Number 372001

Dublin, Ireland

Location

Investigational Site Number 376004

Hadera, Israel

Location

Investigational Site Number 376002

Petah Tikva, 49361, Israel

Location

Investigational Site Number 376003

Tel Aviv, Israel

Location

Investigational Site Number 484004

Guadalajara, 44630, Mexico

Location

Investigational Site Number 484001

México, 07760, Mexico

Location

Investigational Site Number 484002

México, 14000, Mexico

Location

Investigational Site Number 484003

Zapopan, 45200, Mexico

Location

Investigational Site Number 528004

's-Hertogenbosch, Netherlands

Location

Investigational Site Number 528001

Beek, 6191JW, Netherlands

Location

Investigational Site Number 528006

Enschede, 7523JJ, Netherlands

Location

Investigational Site Number 528002

Hoogeveen, 7909AA, Netherlands

Location

Investigational Site Number 528007

Nijverdal, 7442LS, Netherlands

Location

Investigational Site Number 528003

Rotterdam, Netherlands

Location

Investigational Site Number 528005

Woerden, Netherlands

Location

Investigational Site Number 643-009

Kazan', Russia

Location

Investigational Site Number 643008

Kirov, 610014K, Russia

Location

Investigational Site Number 643001

Moscow, 117036, Russia

Location

Investigational Site Number 643004

Saint Petersburg, 195257, Russia

Location

Investigational Site Number 643006

Samara, Russia

Location

Investigational Site Number 643007

Samara, Russia

Location

Investigational Site Number 643005

Saratov, Russia

Location

Investigational Site Number 643003

St-Ptetersburg, 194354, Russia

Location

Investigational Site Number 703002

Bratislava, 81102, Slovakia

Location

Investigational Site Number 703004

Košice, 04013, Slovakia

Location

Investigational Site Number 703001

Nitra, 94911, Slovakia

Location

Investigational Site Number 703005

Nové Mesto nad Váhom, 091501, Slovakia

Location

Investigational Site Number 703003

Žilina, 01001, Slovakia

Location

Investigational Site Number 724007

Bilbao, 48013, Spain

Location

Investigational Site Number 724006

Cadiz, 11009, Spain

Location

Investigational Site Number 724001

Las Palmas de Gran Canaria, 35020, Spain

Location

Investigational Site Number 724005

Lleida, Spain

Location

Investigational Site Number 724008

Madrid, 28040, Spain

Location

Investigational Site Number 724003

Málaga, 29010, Spain

Location

Investigational Site Number 724009

Sabadell, 08208, Spain

Location

Investigational Site Number 721002

Valencia, 46014, Spain

Location

Investigational Site Number 724004

Valencia, 46015, Spain

Location

Investigational Site Number 724010

Vigo, 36211, Spain

Location

Investigational Site Number 752-03

Ängelholm, 26281, Sweden

Location

Investigational Site Number 752-002

Gothenburg, 41665, Sweden

Location

Investigational Site Number 752-005

Karlskoga, 69181, Sweden

Location

Investigational Site Number 752-006

Motala, 59185, Sweden

Location

Investigational Site Number 752-007

Örebro, 70235, Sweden

Location

Investigational Site Number 752-001

Stockholm, 17176, Sweden

Location

Investigational Site Number 792-001

Antalya, 07070, Turkey (Türkiye)

Location

Investigational Site Number 792-002

Istanbul, 34890, Turkey (Türkiye)

Location

MeSH Terms

Conditions

Diabetes Mellitus, Type 2

Interventions

Insulin Glargine; Liraglutide; Metformin

Condition Hierarchy (Ancestors)

Diabetes Mellitus; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases

Intervention Hierarchy (Ancestors)

Insulin, Long-Acting; Insulins; Pancreatic Hormones; Peptide Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Peptides; Amino Acids, Peptides, and Proteins; Glucagon-Like Peptide 1; Glucagon-Like Peptides; Proglucagon; Gastrointestinal Hormones; Biguanides; Guanidines; Amidines; Organic Chemicals

Results Point of Contact

• Title: Trial Transparency Team
• Organization: sanofi

Contact-us@sanofi.com

Study Officials

• Clinical Sciences & Operations

  Sanofi

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 4, 2010
• First Posted: May 5, 2010
• Study Start: July 1, 2010
• Primary Completion: October 1, 2012
• Study Completion: March 1, 2013
• Last Updated: April 11, 2014
• Results First Posted: January 29, 2014

Record last verified: 2014-03

Locations

IE (1); RU (8); CZ (5); IL (3); AU (7); TU (2); FR (14); GR (3); NL (7); BR (6); ES (10); FI (4); CA (6); US (45); SE (6); ME (4); SL (5)