variable bolus regimen 1-2-3 for type 2 diabetes mellitus

Conditions: Diabetes Mellitus, Type 2

Summary: 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.


Eligibility 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.