Characteristics of Glargine in Type 2 Diabetics

NCT ID: NCT00574912

Last Updated: 2017-04-17

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 20 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2007-03-31
• Study Completion Date: 2010-01-31

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.

Conditions

Type 2 Diabetes

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Placebo then Insulin Glargine

Placebo: administer single dose of Placebo subcutaneously (SC) with blood glucose monitoring over 24 hours.

Then Insulin Glargine SQ 8 weeks later, in increasing doses (0.5, 1.0, 1.5, 2.0 u/kg body wt.) with blood glucose monitoring monitoring over a 24 hour period. Each dose is separated by 8 weeks (5 separate study visits)

Group Type: EXPERIMENTAL

Placebo

Intervention Type: DRUG

single dose of Placebo injected s/c at 8am and monitor blood glucose over 24 hours

Insulin Glargine 0.5 u/kg body wt SC

Intervention Type: DRUG

8 weeks later, a differing dose (0.5, 1.0, 1.5, 2.0 u/kg body wt.) of Insulin Glargine and monitoring over a 24 hour period each separated by 8 weeks (5 separate study visits)

Insulin Glargine 1.0 u/kg body wt SC

Intervention Type: DRUG

Insulin Glargine 1.5 u/kg body wt SC

Intervention Type: DRUG

Insulin Glargine 2.0 u/kg body wt SC

Intervention Type: DRUG

Interventions

Placebo

single dose of Placebo injected s/c at 8am and monitor blood glucose over 24 hours

Intervention Type: DRUG

Insulin Glargine 0.5 u/kg body wt SC

8 weeks later, a differing dose (0.5, 1.0, 1.5, 2.0 u/kg body wt.) of Insulin Glargine and monitoring over a 24 hour period each separated by 8 weeks (5 separate study visits)

Intervention Type: DRUG

Insulin Glargine 1.0 u/kg body wt SC

Intervention Type: DRUG

Insulin Glargine 1.5 u/kg body wt SC

Intervention Type: DRUG

Insulin Glargine 2.0 u/kg body wt SC

Intervention Type: DRUG

Other Intervention Names

Lantus; Lantus; Lantus; Lantus; Lantus

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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 70 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Sanofi

INDUSTRY

Sponsor Role: collaborator

Vanderbilt University Medical Center

OTHER

Sponsor Role: lead

Responsible Party

Steve Davis

Chairman of Medicine, University of Maryland, Baltimore

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Stephen N. Davis, MD, FRCP

Role: PRINCIPAL_INVESTIGATOR

Vanderbilt University

Locations

Vanderbilt University

Nashville, Tennessee, United States

Countries

United States

References

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.

Reference Type: DERIVED

PMID: 20357371 (View on PubMed)

Other Identifiers

VUMC 32787

Identifier Type: -

Identifier Source: secondary_id

IRB#060887-Lantus Glargine

Identifier Type: -

Identifier Source: org_study_id