Characteristics of Glargine in Type 2 Diabetics

Phase 1

Completed

• Conditions: Type 2 Diabetes
• Interventions: Drug: Placebo; Drug: Insulin Glargine 0.5 u/kg body wt SC; Drug: Insulin Glargine 1.0 u/kg body wt SC; Drug: Insulin Glargine 1.5 u/kg body wt SC; Drug: Insulin Glargine 2.0 u/kg body wt SC

• Registration Number: NCT00574912
• Lead Sponsor: Vanderbilt University Medical Center

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.

Study Timeline

• Study Start: 2007-03
• Study First Submitted: 2007-12-13
• Study First Submitted QC: 2007-12-13
• Study First Posted: 2007-12-17
• Primary Completion: 2009-09
• Study Completion: 2010-01
• Results First Submitted: 2014-12-18
• Results First Submitted QC: 2015-07-02
• Results First Posted: 2015-08-03
• Status Verified: 2017-03
• Last Update Submitted: 2017-03-17
• Last Update Posted: 2017-04-17

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 20

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

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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

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Placebo then Insulin Glargine	Insulin Glargine 1.5 u/kg body wt SC	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)
Placebo then Insulin Glargine	Insulin Glargine 2.0 u/kg body wt SC	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)
Placebo then Insulin Glargine	Insulin Glargine 0.5 u/kg body wt SC	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)
Placebo then Insulin Glargine	Insulin Glargine 1.0 u/kg body wt SC	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)
Placebo then Insulin Glargine	Placebo	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)

Primary Outcome Measures

Name	Time	Method
Maximum Glucose Infusion Rate	24 hours	measuring the changes in glucose infusion rate during the 24 hour experimental period.

Trial Locations

Locations (1)

Vanderbilt University; 🇺🇸 Nashville, Tennessee, United States