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

Sanofi

Status and phase: Completed; Phase 4

Conditions: Diabetes Mellitus, Type 2

Treatments: Drug: Sitagliptin; Drug: Metformin; Drug: Insulin Glargine

Study type: Interventional

Funder types: Industry

Identifiers

NCT00751114

2008-000516-32 (EudraCT Number)

LANTU_C_02761

Details and patient eligibility

About

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

Enrollment: 515 patients

Sex: All

Ages: 35 to 70 years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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515 participants in 2 patient groups

Insulin Glargine

Experimental group

Description:

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).

Treatment:

Drug: Insulin Glargine

Drug: Metformin

Sitagliptin

Active Comparator group

Description:

Dose of 100 mg once a day administered with or without food.

Treatment:

Drug: Sitagliptin

Drug: Metformin