Insulin Glargine at Bedtime or in AM Versus NPH

The Utility of Insulin Glargine (Lantus) Compared to NPH in Ethnic Minority Type 2 Diabetic Subjects Starting Insulin Therapy

To compare the efficacy and safety of once-nightly insulin glargine versus a single morning injection of glargine or once-nightly NPH insulin in ethnic minority type 2 diabetic patients inadequately controlled on combination oral agents.

Study Overview

• Status: Completed
• Conditions: Type 2 Diabetes Mellitus
• Intervention / Treatment: Drug: 1- Insulin glargine QHS; Drug: 2 - Insulin glargine QAM; Drug: 3 - NPH insulin QHS

Detailed Description

Insulin glargine has a longer action than compared to NPH insulin, but whether this results in improved control when used as a once-nightly or morning basal insulin injection in type 2 diabetic patients who are inadequately controlled on combination oral agents has been controversial. Inner city ethnic minority patients with diabetes are a particularly challenging population of diabetic patients to treat. This study investigates whether insulin glargine may be a more effective or safer first-line basal insulin than NPH in this population.

• Study Type: Interventional
• Enrollment (Actual): 108
• Phase: Phase 4

Contacts and Locations

Study Locations

• United States
  • California
    • Los Angeles, California, United States, 90059
      • Charles Drew University of Medicine and Science

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Male or female, age 18-75
• Type 2 diabetes diagnosed for at least 1 year
• Treatment with stable doses of oral agents (alone or in combination) for at least 2 months
• Inadequate glycemic control (hemoglobin A1c ≥ 7.5%) on maximum-tolerated doses of a sulfonylurea, metformin and a thiazolidinedione
• No past history of chronic insulin use (other than treatment of gestational diabetes or hospitalizations of less than 1 week in duration)
• Hemoglobin A1c between 7.5% and 12%
• Body mass index (BMI) between 20 and 40 kg/m2

Exclusion Criteria:

• Current or previous chronic use of insulin (other than for treatment of gestational diabetes)
• History of confirmed (or clinical suspicion of) type 1 diabetes
• Female subjects of childbearing potential who are sexually active and not using a reliable form of contraception
• Current pregnancy or lactation.
• Subjects for whom insulin therapy is contraindicated or for whom, in the opinion of the investigator, therapy with insulin is not indicated
• Subjects with advanced proliferative diabetic retinopathy
• Subjects who work night shifts or who are unable to stay on a consistent daily meal schedule
• History of any clinically significant renal, hepatic, cardiovascular, neurological, endocrinological or other major systemic disease that, in the opinion of the investigator, may make implementation of the protocol or interpretation of the data difficult.
• Subjects who will likely require or initiate therapy with drugs which may interfere with glucose metabolism during the course of the study
• Subjects who are in another investigational study or have received another investigational medication within 30 days of study entry
• Subjects who are unable or unwilling to comply with all components of the study protocol, including contacting the investigators at specified times and attending all scheduled follow-up visits.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 1 - Insulin glargine QHS; Insulin glargine injected subcutaneously once daily at bedtime	Drug: 1- Insulin glargine QHS; Insulin glargine at bedtime (dose titrated to maintain 50% of fasting glucose readings <120 mg/dL); Other Names: Trade name: Lantus
Experimental: 2 - Insulin glargine QAM; Insulin glargine injected subcutaneously once daily in the morning	Drug: 2 - Insulin glargine QAM; Insulin glargine in AM (dose titrated to maintain 50% of pre-supper glucose readings <120 mg/dL); Other Names: Trade name: Lantus
Active Comparator: 3 - NPH Insulin QHS; NPH insulin injected subcutaneously once daily at bedtime	Drug: 3 - NPH insulin QHS; NPH insulin at bedtime (dose titrated to maintain 50% of fasting glucoses <120 mg/dL); Other Names: (Generic)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Hemoglobin A1c Change From Baseline	Baseline to 6 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Frequency of Glucose Readings < 130 mg/dL	Frequency of glucose readings below the recommended pre-meal glucose target of 130 mg/dL	6 months
Frequency of Total Hypoglycemic Reactions	Frequency of hypoglycemic reactions without regard to time of occurrence	6 months
Frequency of Severe Hypoglycemic Reactions	Frequency of severe hypoglycemic reactions, defined as those requiring the assistance of another person	6 months
Body Mass Index Change From Baseline	Change in body mass index from baseline BMI measurement	6 months
Total Daily Insulin Dose	Total daily number of units of insulin used	6 months
Any Adverse Event Other Than Hypoglycemia	Any reported adverse event that is not hypoglycemia	6 months

Collaborators and Investigators

• Sponsor: Charles Drew University of Medicine and Science
• Collaborators: National Center for Research Resources (NCRR)

Publications and helpful links

General Publications

• Semlitsch T, Engler J, Siebenhofer A, Jeitler K, Berghold A, Horvath K. (Ultra-)long-acting insulin analogues versus NPH insulin (human isophane insulin) for adults with type 2 diabetes mellitus. Cochrane Database Syst Rev. 2020 Nov 9;11(11):CD005613. doi: 10.1002/14651858.CD005613.pub4.
• Hsia SH. Insulin glargine compared to NPH among insulin-naive, U.S. inner city, ethnic minority type 2 diabetic patients. Diabetes Res Clin Pract. 2011 Mar;91(3):293-9. doi: 10.1016/j.diabres.2010.11.028. Epub 2010 Dec 13.

Study record dates

Study Major Dates

• Study Start: February 1, 2003
• Primary Completion (Actual): August 1, 2009
• Study Completion (Actual): August 1, 2009

Study Registration Dates

• First Submitted: May 27, 2008
• First Submitted That Met QC Criteria: May 29, 2008
• First Posted (Estimate): May 30, 2008

Study Record Updates

• Last Update Posted (Actual): May 22, 2017
• Last Update Submitted That Met QC Criteria: April 18, 2017
• Last Verified: April 1, 2017

More Information

Terms related to this study

• Keywords: Type 2 diabetes; Glargine; Basal insulin
• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Endocrine System Diseases; Diabetes Mellitus; Diabetes Mellitus, Type 2; Hypoglycemic Agents; Physiological Effects of Drugs; Insulin; Insulin, Globin Zinc; Insulin Glargine; Insulin, Isophane; Isophane Insulin, Human; Isophane insulin, beef
• Other Study ID Numbers: 03-02-524; U54RR014616 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO