Variable Bolus Regimen 1-2-3 for Type 2 Diabetes Mellitus

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Status and phase

Phase 3


Diabetes Mellitus, Type 2


Drug: insulin glulisine

Study type


Funder types




Details and patient eligibility


The purpose of this study is to show the non-inferiority of insulin glulisine administered with 1 meal versus 2 meals versus 3 daily meals, as measured by the change in hemoglobin A1c (HbA1c), from baseline to study week 24.


347 patients




18 to 79 years old


No Healthy Volunteers

Inclusion and exclusion criteria

Subjects with type 2 diabetes mellitus who have been using a stable combination oral antidiabetic therapy of 2 or 3 agents in different therapeutic classes for on at least 3 months will be enrolled in this study.

Inclusion Criteria:

  • Male and female subjects 18 to 79 years of age with a diagnosis of type 2 diabetes mellitus for at least 6 months

  • Current treatment with a stable dose of 2 oral antidiabetic agents. The oral agents must be in 2 or 3 of the following 3 different classes:

    • Sulfonylurea: dosage greater than or equal to, one-half the maximum recommended dosage (eg, glimepiride >/= 4 mg; glipizide, including gastrointestinal therapeutic system [GITS], >/= 10 mg; glyburide >/= 10 mg; Glynase® >/=3 mg). The dosage must have been stable for at least 3 months prior to screening.
    • Biguanide: metformin dosage ≥ 1000 mg daily, including Glucophage XR®. The dosage must have been stable for at least 3 months prior to screening.
    • Thiazolidinedione (TZD): pioglitazone >/= 15 mg or rosiglitazone >/= 24 mg. The subject must have been using the same thiazolidinedione for at least 6 months,and the dosage must have been stable for at least 3 months prior to screening.
  • HbA1c >/= 8.0%

  • Fasting C-peptide concentration > 0.27 nmol/L

  • Able and willing to perform self-monitoring of blood glucose (SMBG) up to 4 times a day

  • Able and willing to adhere to, and be compliant with, the study protocol

  • Able to read English or Spanish at the sixth-grade level in order to complete the subject reported outcomes component of the study

  • Signed informed consent and Health Insurance Portability and Accountability Act (HIPAA) authorization

Exclusion Criteria:

  • Insulin use within the previous year
  • History of hypoglycemia unawareness
  • Acute or chronic, or history of, metabolic acidosis, including diabetic ketoacidosis
  • Impaired renal function as shown by, but not limited to, serum creatinine ≥ 3mg/dL. For subjects taking metformin, serum creatinine >/= 1.5 mg/dL for males, or >/= 1.4 mg/dL for females.
  • Serum alanine aminotransferase (ALT) or aspartate aminotransferase (AST) levels greater than 2.5 times the upper limit of normal (ULN)
  • Clinically significant peripheral edema if subject is using a TZD
  • History of stroke, myocardial infarction, coronary artery bypass graft, percutaneous transluminal coronary angioplasty, or angina pectoris, within the past 12 months
  • History of, or current, congestive heart failure (New York Heart Association [NYHA] III-IV) requiring pharmacologic treatment
  • Acute infection
  • Any malignancy within the past 5 years, with the exception of adequately treated basal or squamous cell carcinoma or adequately treated cervical carcinoma in situ
  • Current substance addiction or alcohol abuse or history of substance or alcohol abuse, within the past 2 years
  • Any clinically significant renal disease (other than proteinuria) or hepatic disease
  • Pregnant or lactating females
  • Dementia or mental condition rendering the subject unable to understand the nature, scope, and possible consequences of the study
  • Impaired dexterity or vision rendering the subject unable to administer injections
  • Known hypersensitivity to insulin glargine or insulin glulisine or any of the components of Lantus or Apidra
  • Any disease or condition (including abuse of illicit drugs, prescription medications, or alcohol) that, in the opinion of the investigator or sponsor, may interfere with the completion of the study
  • Unlikely to comply with the protocol, eg, uncooperative attitude, inability to return for follow-up visits, or unlikely to complete the study
  • Subject 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
  • No subject will be allowed to enroll in this study more than once.

Trial design

Primary purpose




Interventional model

Parallel Assignment


None (Open label)

347 participants in 3 patient groups

Experimental group
Once daily: Insulin glulisine Dosing: Supper, Lunch, Breakfast Monitoring Needed at: Bedtime,Pre-Supper, Pre-Lunch
Drug: insulin glulisine
Experimental group
Twice daily: Insulin glulisine Dosing: Supper & Lunch, Lunch & Breakfast, Breakfast & Supper Monitoring Needed at: Bedtime & Pre-Supper, Pre-Supper & Pre-Lunch, Pre-Lunch & Bedtime
Drug: insulin glulisine
Experimental group
Twice daily: Insulin glulisine Dosing: Supper, Lunch, Breakfast Monitoring Needed at: Bedtime, Pre-Supper, Pre-Lunch
Drug: insulin glulisine

Trial contacts and locations



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