Bedtime Insulins and Oral Antihyperglycemic Drugs in Type 2 Diabetes

University of Campania "Luigi Vanvitelli"

Status and phase

Completed

Phase 4

Conditions

Hypoglycemia

Type 2 Diabetes Mellitus

Treatments

Drug: NPL insulin

Drug: Insulin glargine

Study type

Interventional

Funder types

Other

Identifiers

NCT00641407

DGMM-01/2006

Details and patient eligibility

About

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.

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 Before the start of insulin therapy, and at weeks 12, 24 and 36, blood was withdrawn for measurements of full blood counts, electrolytes, creatinine, liver enzymes and lipids.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

Enrollment

100 patients

Sex

All

Ages

30 to 70 years old

Volunteers

No Healthy Volunteers

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