Bedtime Insulins and Oral Antihyperglycemic Drugs in Type 2 Diabetes
Information source: Second University of Naples
ClinicalTrials.gov processed this data on August 23, 2015 Link to the current ClinicalTrials.gov record.
Condition(s) targeted: Type 2 Diabetes Mellitus; Hypoglycemia
Intervention: NPL insulin (Drug); Insulin glargine (Drug)
Phase: Phase 4
Status: Completed
Sponsored by: Second University of Naples Official(s) and/or principal investigator(s): Dario Giugliano, MD,PhD, Principal Investigator, Affiliation: Department of Geriatrics and Metabolic Diseases
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.
Clinical Details
Official title: Bedtime Insulin Glargine or Bedtime Neutral Protamine Lispro Combined With Sulfonylurea and Metformin in Type 2 Diabetes. A Randomized, Controlled Trial
Study design: Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment
Primary outcome: Change in hemoglobin A1c (HbA1c) level from baseline to end point for each treatment group.
Secondary outcome: 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.
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
Minimum age: 30 Years.
Maximum age: 70 Years.
Gender(s): Both.
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
Locations and Contacts
Department of Geriatrics and Metabolic Disease, Naples 80138, Italy
Additional Information
Related publications: Yki-Järvinen H, Kauppinen-Mäkelin R, Tiikkainen M, Vähätalo M, Virtamo H, Nikkilä K, Tulokas T, Hulme S, Hardy K, McNulty S, Hänninen J, Levänen H, Lahdenperä 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. Epub 2006 Feb 3. Fritsche A, Schweitzer MA, Häring 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. 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.
Starting date: January 2007
Last updated: March 28, 2008
|