Evaluation of Insulin Glargine Versus Sitagliptin in Insulin-naive Patients (EASIE)

Superiority Study of Insulin Glargine Over Sitagliptin in Insulin-naïve Patients With Type 2 Diabetes Treated With Metformin and Not Adequately Controlled

The primary objective was to demonstrate the superiority of insulin glargine over sitagliptin in reducing Glycosylated Hemoglobin A1c (HbA1c) from baseline to the end of the treatment period.

Secondary objective was to assess the effect of insulin glargine in comparison with sitagliptin on:

• HbA1c level
• Fasting Plasma Glucose (FPG)
• 7-point plasma glucose (PG) profiles
• Percentage of patients with HbA1c <7% and <6.5%

Safety objectives consisted of:

• Hypoglycemia occurrence
• Body weight
• Overall safety

Study Overview

• Status: Completed
• Conditions: Diabetes Mellitus, Type 2
• Intervention / Treatment: Drug: Metformin; Drug: Insulin Glargine; Drug: Sitagliptin

• Study Type: Interventional
• Enrollment (Actual): 515
• Phase: Phase 4

Contacts and Locations

Study Locations

• Austria
  • Vienna, Austria
    • Sanofi-Aventis Administrative Office
• Brazil
  • Sao Paulo, Brazil
    • Sanofi-Aventis Administrative Office
• Colombia
  • Bogota, Colombia
    • Sanofi-Aventis Administrative Office
• Egypt
  • Cairo, Egypt
    • Sanofi-Aventis Administrative Office
• Greece
  • Kallithea, Greece
    • Sanofi-Aventis Administrative Office
• Hong Kong
  • Hong Kong, Hong Kong
    • Sanofi-Aventis Administrative Office
• India
  • Mumbai, India
    • Sanofi-Aventis Administrative Office
• Israel
  • Natanya, Israel
    • Sanofi-Aventis Administrative Office
• Korea, Republic of
  • Seoul, Korea, Republic of
    • Sanofi-Aventis Administrative Office
• Lebanon
  • Beirut, Lebanon
    • Sanofi-Aventis Administrative Office
• Mexico
  • Col. Coyoacan, Mexico
    • Sanofi-Aventis Administrative Office
• Netherlands
  • Gouda, Netherlands
    • Sanofi-Aventis Administrative Office
• Portugal
  • Porto Salvo, Portugal
    • Sanofi-Aventis Administrative Office
• Spain
  • Barcelona, Spain
    • Sanofi-Aventis Administrative Office
• Turkey
  • Istanbul, Turkey
    • Sanofi-Aventis Administrative Office
• United Kingdom
  • Guildford Surrey, United Kingdom
    • Sanofi-Aventis Administrative Office
• United States
  • New Jersey
    • Bridgewater, New Jersey, United States, 08807
      • Sanofi-Aventis Administrative Office

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 35 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• With type 2 diabetes diagnosed for at least 6 months,
• Not previously treated with insulin,
• On metformin for at least 3 months and a stable minimal dose of 1 g/day for at least 2 months
• HbA1c ≥ 7 and < 11 %,
• Body Mass Index (BMI) between 25 and 45 kg/m² inclusively,
• Ability and willingness to perform plasma glucose (PG) monitoring using the Sponsor-provided PG meter and to complete the patient diary,
• Signed informed consent obtained prior any study procedures,
• Willingness and ability to comply with the study protocol.

Exclusion Criteria:

• Treatment with oral antidiabetic drugs other than metformin within the last 3 months,
• Previous treatment with the combination of metformin + sulfonylurea for more than 1 year,
• Previous treatment with Glucagon Like Peptide-1 (GLP-1) agonists or DiPeptidyl Peptidase (DPP) IV inhibitors,
• FPG (assessed by central laboratory measurement) ≥ 280 mg/dL (15.4 mmol/L),
• Diabetes other than type 2 diabetes (e.g. secondary to pancreatic disorders, drug or chemical agents intake...),
• Pregnant or lactating women (women of childbearing potential must have a negative pregnancy test at study entry and a medically approved contraception method),
• In-patient care,
• Active proliferative retinopathy, as defined by a photocoagulation or vitrectomy occurrence in the 6 months prior to visit 1, or any other unstable (rapidly progressing) retinopathy that may require photocoagulation or surgical treatment during the study (an optic fundus examination should have been performed within the 2 years prior to study entry),
• Impaired renal function: serum creatinine ≥ 1.5 mg/dL (≥ 133µmol/L) or ≥ 1.4 mg/dL (≥ 124 µmol/L) in men and women, respectively,
• History of sensitivity to the study drugs or to drugs with a similar chemical structure,
• Impaired hepatic function: alanine aminotransferase (ALT), aspartate aminotransferase (AST) > 3 x upper limit of normal range,
• Treatment with systemic corticosteroids within the 3 months prior to study entry or likelihood of requiring treatment during the study that are not permitted during the study (exception: in case of chronic adrenal insufficiency, systemic glucosteroids are accepted only if the disease is stable and the treatment dose stable for at least 3 months before study entry),
• Alcohol or drug abuse within the last year,
• Night shift worker,
• Presence of any condition (medical, psychological, social or geographical), current or anticipated that the investigator feels would compromise the patient's safety or limit the patient successful participation in the study,
• Treatment with weight loss medications (e.g. sibutramine, orlistat, rimonabant) within the last 3 months,
• Participation in another clinical trial within the month prior to visit 1,
• History of pancreatitis.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Insulin Glargine; Administered once a day in the evening at dinner or at bedtime with a starting dose 0.2 U/kg. Then, the doses were to be individually adjusted, following a titration algorithm, to reach the FPG target: 70mg/dL<FPG≤100mg/dL (3.9mmol/L<FPG≤5.5mmol/L).	Drug: Metformin; Patients continued with metformin as usual oral anti-diabetic treatment.; Drug: Insulin Glargine; Subcutaneous injection. 100 Units/mL solution for injection in a pre-filled SoloStar® pen (3 mL).; Other Names: Lantus®
Active Comparator: Sitagliptin; Dose of 100 mg once a day administered with or without food.	Drug: Metformin; Patients continued with metformin as usual oral anti-diabetic treatment.; Drug: Sitagliptin; Oral administration. 100 mg film-coated tablets.; Other Names: Januvia®

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
HbA1c: Change From Baseline to Study Endpoint	Change in HbA1c from baseline to study endpoint defined as the last available HbA1c value measured during the 24-week treatment period.	baseline (week 0), study endpoint: visit 14 (week 24) or visit 11 (week 12) if value not available at visit 14

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
HbA1c Response Rate: Percentage of Patients Who Reach the Target of HbA1c < 7% at Study Endpoint		study endpoint: visit 14 (week 24) or visit 11 (week 12) if value not available at visit 14
HbA1c Response Rate: Percentage of Patients Who Reach the Target of HbA1c < 6.5% at Study Endpoint		study endpoint: visit 14 (week 24) or visit 11 (week 12) if value not available at visit 14
Self-monitored Fasting Plasma Glucose (SMFPG) Mean : Change From Baseline to Study Endpoint	SMFPG mean = mean of the fasting plasma glucose values recorded on the 6 consecutive days before the visit (at least 3 values needed). Study endpoint was defined as the last available SMFPG mean value collected on-treatment. Change= study endpoint - baseline	baseline (week 0), study endpoint: visit 14 (week 24) or visit 12 (week 16) or visit 11 (week 12) or visit 8 (week 6) depending on last available value
7-point Plasma Glucose Profile: Change From Baseline to Study Endpoint	7-point plasma glucose recorded before and after breakfast, before and after lunch, before and after dinner and at bedtime. Change = study endpoint - baseline.	baseline (week 0), study endpoint: visit 14 (week 24) or visit 11 (week 12) if value not available at visit 14
Insulin Dose in the Insulin Glargine Group	Daily dose at the face-to-face visits.	visit 4 (week 2), visit 8 (week 6), visit 11 (week 12), visit 12 (week 16), visit 14 (week 24), first dose received defined as first available value, study endpoint defined as last available value
Lipid Profile: Change From Baseline to Study Endpoint		baseline (week 0), study endpoint: visit 14 (week 24) or visit 11 (week 12) if value not available at visit 14
Change in Body Weight From Baseline to Study Endpoint		baseline (week 0), study endpoint: visit 14 (week 24) or visit 12 (week 16) or visit 11 (week 12) or visit 8 (week 6) depending on last available value
Number of Patients With at Least One Episode of Symptomatic Hypoglycemia	Symptomatic hypoglycemia was defined as an event with clinical symptoms that were considered to result from hypoglycemia confirmed or not by a plasma glucose measurement <= 70mg/dL [3.9 mmol/L]	During the treatment phase (24 weeks) plus 7 days after last dose
Number of Patients With at Least One Episode of Severe Symptomatic Hypoglycemia	Severe symptomatic hypoglycemia was defined as an event with clinical symptoms which required assistance of another person and with either a Plasma Glucose level < 36 mg/dL (2 mmol/L) or with a prompt recovery after oral carbohydrate, intravenous glucose, or glucagon administration	During the treatment phase (24 weeks) plus 7 days after last dose

Collaborators and Investigators

• Sponsor: Sanofi

Publications and helpful links

General Publications

• Aschner P, Chan J, Owens DR, Picard S, Wang E, Dain MP, Pilorget V, Echtay A, Fonseca V; EASIE investigators. Insulin glargine versus sitagliptin in insulin-naive patients with type 2 diabetes mellitus uncontrolled on metformin (EASIE): a multicentre, randomised open-label trial. Lancet. 2012 Jun 16;379(9833):2262-9. doi: 10.1016/S0140-6736(12)60439-5. Epub 2012 Jun 9.
• Chan JC, Aschner P, Owens DR, Picard S, Vincent M, Dain MP, Pilorget V, Loizeau V, Echtay A, Fonseca V. Triple combination of insulin glargine, sitagliptin and metformin in type 2 diabetes: the EASIE post-hoc analysis and extension trial. J Diabetes Complications. 2015 Jan-Feb;29(1):134-41. doi: 10.1016/j.jdiacomp.2014.08.007. Epub 2014 Aug 27.

Study record dates

Study Major Dates

• Study Start: November 1, 2008
• Primary Completion (Actual): July 1, 2011
• Study Completion (Actual): July 1, 2011

Study Registration Dates

• First Submitted: September 10, 2008
• First Submitted That Met QC Criteria: September 10, 2008
• First Posted (Estimate): September 11, 2008

Study Record Updates

• Last Update Posted (Estimate): September 10, 2012
• Last Update Submitted That Met QC Criteria: September 3, 2012
• Last Verified: September 1, 2012

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Endocrine System Diseases; Diabetes Mellitus; Diabetes Mellitus, Type 2; Hypoglycemic Agents; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Protease Inhibitors; Incretins; Dipeptidyl-Peptidase IV Inhibitors; Metformin; Insulin Glargine; Sitagliptin Phosphate
• Other Study ID Numbers: LANTU_C_02761; 2008-000516-32 (EudraCT Number)