Bedtime Insulins and Oral Antihyperglycemic Drugs in Type 2 Diabetes

This study has been completed.
Sponsor:
Information provided by:
Second University of Naples
ClinicalTrials.gov Identifier:
NCT00641407
First received: March 17, 2008
Last updated: March 28, 2008
Last verified: March 2008
  Purpose

The maintenance of nearly normal glycemic levels reduces the risk of diabetic complications, but is difficult to achieve, despite the administration of escalating doses of oral antidiabetic drugs, such as metformin, sulfonylureas, and thiazolidinediones. Most patients eventually require insulin which usually is added when glycemic control with a regimen of oral antidiabetic agents becomes suboptimal.

The aims of the present study were: 1) To compare the clinical efficacy of insulin glargine and neutral protamine lispro (NPL) insulin when added to ongoing oral therapy in poorly controlled type 2 diabetic patients; 2) to find out the possibility to phenotype the patient who may benefit more by the single treatment.

This an open-label, randomized, parallel, 36-week comparative study was performed between January 2007 and March 2008 at a single centre.


Condition Intervention Phase
Type 2 Diabetes Mellitus
Hypoglycemia
Drug: NPL insulin
Drug: Insulin glargine
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Bedtime Insulin Glargine or Bedtime Neutral Protamine Lispro Combined With Sulfonylurea and Metformin in Type 2 Diabetes. A Randomized, Controlled Trial

Resource links provided by NLM:


Further study details as provided by Second University of Naples:

Primary Outcome Measures:
  • Change in hemoglobin A1c (HbA1c) level from baseline to end point for each treatment group. [ Time Frame: 9 months ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Percentage of subjects achieving HbA1c ≤7%, incidence of self-reported hypoglycaemic episodes, comparison of SMPG values from 8-point profiles, insulin doses, and body weight. [ Time Frame: 9 months ] [ Designated as safety issue: Yes ]

Enrollment: 100
Study Start Date: January 2007
Study Completion Date: March 2008
Primary Completion Date: December 2007 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 1 Drug: NPL insulin
Starting dose 10 IU bedtime and then titration
Active Comparator: 2 Drug: Insulin glargine
10 IU bedtime and then titration

Detailed Description:

Patients were randomized to either NPL (Lilly) or glargine (Lantus, Aventis) to be administered subcutaneously at bedtime. Both insulin formulations consisted of cartridge containing 3 ML of either insulin preparation. Oral antihyperglycemic agents were continued at the prestudy dosages. No dietary advice was given beyond reinforcement of standard guidelines. The initial bedtime insulin dose was 10 IU for all patients with the goal to achieve a target FPG of < 100 mg/dL in both groups. The insulin dose was titrated weekly according to daily self-monitored fasting blood glucose measurements that provide values corresponding closely to laboratory measurements of plasma glucose. The patients were taught to increase their insulin dose by 2 IU if FPG was greater than 100 mg/dL, and by 4 IU if FPG was greater than 180 mg/dL on three consecutive mornings. Before the start of insulin therapy, and at weeks 12, 24 and 36, blood was withdrawn for measurements of full blood counts, electrolytes, creatinine, liver enzymes and lipids. Insulin doses, self-monitored plasma glucose (SMPG), and any events associated with signs or symptoms of hypoglycaemia were recorded in diaries.

  Eligibility

Ages Eligible for Study:   30 Years to 70 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Men and women aged 30-70 years, with a duration of known diabetes > 2 years
  • And treated with stable doses of two oral antihyperglycemic agents (metformin and sulfonylurea) for at least 90 days were selected for the study
  • Body mass index less than 40 kg/m2
  • HbA1c level between 7.5 and 10%
  • And fasting plasma glucose of 120 mg/dL or greater.

Exclusion Criteria:

  • Exclusion criteria included pregnancy or breast-feeding
  • Previous use of insulin or other antihyperglycemic drugs
  • Investigational drug within the previous 3 months
  • Use of agents affecting glycemic control (systemic glucocorticoids, and weight-loss drugs)
  • Presence of any clinically relevant somatic or mental diseases
  • To minimize the likelihood of including subjects with late-onset type 1 diabetes
  • Candidate with a positive test for anti-GAD antibody or with fasting plasma C-peptide less than 0.25 pmol/ml were excluded
  • Also excluded were patients with abnormal safety laboratory tests
  • Including liver enzymes (ALT, AST, AFOS) higher than three times the upper limit of normal and serum creatinine > 1.4 mg/dL)
  • History of drug abuse
  • Poor compliance with the 8-point daily glucose profile measurement
  Contacts and Locations
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Please refer to this study by its ClinicalTrials.gov identifier: NCT00641407

Locations
Italy
Department of Geriatrics and Metabolic Disease
Naples, Italy, 80138
Sponsors and Collaborators
Second University of Naples
Investigators
Principal Investigator: Dario Giugliano, MD,PhD Department of Geriatrics and Metabolic Diseases
  More Information

Publications:
Responsible Party: Dario Giugliano, MD, PhD, Department of Geriatrics and Metabolic Diseases
ClinicalTrials.gov Identifier: NCT00641407     History of Changes
Other Study ID Numbers: DGMM-01/2006
Study First Received: March 17, 2008
Last Updated: March 28, 2008
Health Authority: Italy: Ethics Committee

Keywords provided by Second University of Naples:
Bedtime insulins
Poorly controlled type 2 diabetes
Glycemic control
HbA1c

Additional relevant MeSH terms:
Diabetes Mellitus
Diabetes Mellitus, Type 2
Hypoglycemia
Endocrine System Diseases
Glucose Metabolism Disorders
Metabolic Diseases
Glargine
Insulin
Insulin, Globin Zinc
Hypoglycemic Agents
Pharmacologic Actions
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on October 23, 2014