Bedtime Insulins and Oral Antihyperglycemic Drugs in Type 2 Diabetes

NCT ID: NCT00641407

Last Updated: 2008-03-31

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE4
• Total Enrollment: 100 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2007-01-31
• Study Completion Date: 2008-03-31

Brief Summary

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.

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 Before the start of insulin therapy, and at weeks 12, 24 and 36, blood was withdrawn for measurements of full blood counts, electrolytes, creatinine, liver enzymes and lipids.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.

Conditions

Type 2 Diabetes Mellitus; Hypoglycemia

Keywords

Bedtime insulins; Poorly controlled type 2 diabetes; Glycemic control; HbA1c

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

1

Group Type: EXPERIMENTAL

NPL insulin

Intervention Type: DRUG

Starting dose 10 IU bedtime and then titration

2

Group Type: ACTIVE_COMPARATOR

Insulin glargine

Intervention Type: DRUG

10 IU bedtime and then titration

Interventions

NPL insulin

Starting dose 10 IU bedtime and then titration

Intervention Type: DRUG

Insulin glargine

10 IU bedtime and then titration

Intervention Type: DRUG

Eligibility 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

• 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

• Minimum Eligible Age: 30 Years
• Maximum Eligible Age: 70 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

University of Campania Luigi Vanvitelli

OTHER

Sponsor Role: lead

Responsible Party

Department of Geriatrics and Metabolic Diseases

Principal Investigators

Dario Giugliano, MD,PhD

Role: PRINCIPAL_INVESTIGATOR

Department of Geriatrics and Metabolic Diseases

Locations

Department of Geriatrics and Metabolic Disease

Naples, , Italy

Countries

Italy

References

Yki-Jarvinen H, Kauppinen-Makelin R, Tiikkainen M, Vahatalo M, Virtamo H, Nikkila K, Tulokas T, Hulme S, Hardy K, McNulty S, Hanninen J, Levanen H, Lahdenpera S, Lehtonen R, Ryysy L. Insulin glargine or NPH combined with metformin in type 2 diabetes: the LANMET study. Diabetologia. 2006 Mar;49(3):442-51. doi: 10.1007/s00125-005-0132-0. Epub 2006 Feb 3.

Reference Type: BACKGROUND

PMID: 16456680 (View on PubMed)

Fritsche A, Schweitzer MA, Haring HU; 4001 Study Group. Glimepiride combined with morning insulin glargine, bedtime neutral protamine hagedorn insulin, or bedtime insulin glargine in patients with type 2 diabetes. A randomized, controlled trial. Ann Intern Med. 2003 Jun 17;138(12):952-9. doi: 10.7326/0003-4819-138-12-200306170-00006.

Reference Type: BACKGROUND

PMID: 12809451 (View on PubMed)

Nathan DM, Buse JB, Davidson MB, Ferrannini E, Holman RR, Sherwin R, Zinman B. Management of hyperglycemia in type 2 diabetes: a consensus algorithm for the initiation and adjustment of therapy: update regarding thiazolidinediones: a consensus statement from the American Diabetes Association and the European Association for the Study of Diabetes. Diabetes Care. 2008 Jan;31(1):173-5. doi: 10.2337/dc08-9016. No abstract available.

Reference Type: BACKGROUND

PMID: 18165348 (View on PubMed)

Other Identifiers

DGMM-01/2006

Identifier Type: -

Identifier Source: org_study_id