Clinical trial NCT00574912: Characteristics of Glargine in Type 2 Diabetics
Official title: A Comparison of PK/PD Dose Response Characteristics of Glargine in Type 2 Diabetics
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Type 2 Diabetes
Keywords: Type 2 diabetes
Insulin Glargine
Endogenous Glucose Production
Lead sponsor: Vanderbilt University Medical Center
Sponsor class: OTHER
Collaborators: name: Sanofi
First posted: 2007-12-17
Enrollment: 20
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: The study is to determine the dose response relationship of insulin glargine in type 2 diabetes over a 24-hour period and measuring the differences in glucose production among the differing doses of glargine.

Hypothesis: Differing doses of insulin glargine over a 24-hour period in type 2 diabetes will show differing effects on endogenous glucose production, glucose disposal and carbohydrate and lipid flux.

Detailed description: 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.

Eligibility criteria: 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

Primary outcomes:
measure: Maximum Glucose Infusion Rate
timeFrame: 24 hours
Secondary outcomes:
Other outcomes:
Locations:
city: Nashville
country: United States
facility: Vanderbilt University
state: Tennessee
Study officials:
affiliation: Vanderbilt University
name: Stephen N. Davis, MD, FRCP
role: PRINCIPAL_INVESTIGATOR
References:
citation: Wang Z, Hedrington MS, Gogitidze Joy N, Briscoe VJ, Richardson MA, Younk L, Nicholson W, Tate DB, Davis SN. Dose-response effects of insulin glargine in type 2 diabetes. Diabetes Care. 2010 Jul;33(7):1555-60. doi: 10.2337/dc09-2011. Epub 2010 Mar 31.