Characteristics of Glargine in Type 2 Diabetics

The incidence of type 2 DM is increasing worldwide at an alarming rate. Unfortunately, the
number of individuals with glycemic control at or below the American Diabetes Association
goal of 7% has dropped. In fact, the number of patients with their important cardiometabolic
risk factors of glucose, lipids and blood pressure at goal is only 7%. One of the reasons
for this lack of metabolic control in type 2 DM is the continued relative underutilization
of insulin. Diabetes is an insulin deficient state and requires appropriate physiologic
replacement of insulin. Physiologic replacement of insulin requires a basal component to
restrain overnight endogenous glucose production, lipolysis and proteolysis. The other
component involves prandial insulin to regulate post prandial glucose levels. Recently,
insulin glargine was introduced as a once-a-day peakless basal insulin. This form of basal
insulin reproduces the normal constitutive physiologic release of insulin from the pancreas.
Insulin glargine represents a breakthrough in treatment as the previous available "basal
insulins" either produced peaks of activity (which are disadvantageous as this results in
hypoglycemia) or do not last 24 hrs which results in post absorbative hyperglycemia. Despite
the undoubted advantages of insulin glargine, there remains a lack of information regarding
some aspects of glargine action. The study objectives are: 1) to determine the
pharmacokinetic and pharmacodynamic dose response relationship of insulin glargine in Type 2
DM; 2) partition the dose response relationship of insulin glargine on endogenous glucose
production and glucose uptake in Type 2 DM; and 3) to determine if the pharmacokinetic and
pharmacodynamics of insulin glargine are consistent over a wide range of doses.

Inclusion Criteria:

- 12 adults (males or females) with type 2 diabetes for at least six (6) months. May be
using oral agents (SUs, metformin, acarbose or glitinides) with or without insulin.

- HgbA1c 7 -12%

- Age 18-70 years

- BMI 27-40 kg/m²

Exclusion Criteria:

- Any past or present clinically relevant abnormality, medical condition, or
circumstance making the subject unsuitable for participation in the study

- Evidence of hepatic, renal or cardiac failure

- Abnormal results following screening tests

- Pregnant or lactating females or females of childbearing potential who are unwilling
to abstain from sexual intercourse or use reliable, medically accepted methods of
contraception

- Currently using TZDs

- History of alcoholism or drug abuse within 12 months of the study