Official Title: “New Approach to Treat Type II Diabetes Failing on Maximal Oral Treatment”

Many diabetics gain weight while on insulin therapy. In this study, we evaluate the efficacy of the combination of glimepiride and short-acting insulin on weight control and glucose control. In this study, 150 diabetics whose diabetic control is inadequate while on maximal oral treatment will be randomized to either the new combination treatment or twice daily injections with a mixture of short- and longacting insulin or once-daily injection with a basal insulin analog. The study will compare glucose control and weight gain during a year after randomisation between the three treatments.

Study Type: Interventional

Study Design: Treatment, Randomized, Open Label, Active Control, Parallel Assignment, Safety/Efficacy Study

Diabetic patients failing on maximal oral treatment usually switch to twice daily administration of a mixture of short- and longacting insulin. Although this improves glycemic control, it is generally accompanied by a substantial gain in body weight. This may lead to an increase in body fat resulting in a worsening of insulin resistance, leading to an increase in insulin dose needed to maintain glycemic control.

The combination of glimepiride(amaryl) and short-acting insulin (novorapid) is thought to attain glycemic control with a smaller increase in body weight.

In this randomized controlled trial, 150 diabetics failing on maximal oral treatment will be randomized to preprandial use of Novorapid combined with Amaryl at 20.00 hours, twice daily Novomix 30, or once daily Lantus. Metformin will be continued.

In the year after randomisation, patients will be followed for glycemic control, body weight, body composition, recorded number of hypoglycemic events, plasma lipid levels, basal and stimulated C-peptide levels and adverse effects.

Intervention(s) in this Clinical Trial

• Drug: Novomix 30
• Drug: Novorapid and Amaryl
• Drug: Lantus

Primary Measures

• glycemic control based on HbA1c
• Body weight

Secondary Measures

• 8-point glucose day curve of three consecutive days
• 24-hour glycemic control measured by continuous glucose monitoring for three consecutive days
• recorded number of hypoglycemic events per month
• waist circumference
• dexa measurements of body composition
• plasma lipid levels
• basal and stimulated C-peptide levels
• adverse effects

Inclusion Criteria:

• failing maximal oral treatment, defined as mean fasting blood glucose over 8 mmol/l and HbA1C over 7.5% for three months or more
• BMI 25 - 35 kg/m2
• fasting plasma C-peptide level over 0.3 nmol/l
• stable metformin and sulfonylurea dose for at least three months
• stable weight for at least three months (change maximal 2 kg)

Exclusion Criteria:

• fasting glucose over 25 mmol/l
• use of alpha-glucosidase inhibitors or thiazolidinediones in the two months preceding the study
• renal or liver failure defined as serum creatinine over 150 micromol/l, liver enzymes over 1.5 upper normal limit
• heart failure
• pregnancy
• alcohol more than two units per day
• inflammatory or infectious diseases
• unstable chronic disease
• discontinuation of smoking within three months of randomisation date
• allergy for or intolerance of glimepiride or novorapid.

Gender Eligibility for this Clinical Trial: Both

Minimum Age for this Clinical Trial: 30 Years

Maximum Age for this Clinical Trial: 75 Years

Are Healthy Volunteers Accepted for this Clinical Trial?: No

Lead Sponsor: Rijnstate Hospital

Overall Clinical Trial Officials and Contacts

Hans de Boer, MD, PhD Principal Investigator Rijnstate Hospital  

Overall Contact: Hans de Boer, MD, PhD +31-263788888 HdeBoer@alysis.nl

Information obtained from ClinicalTrials.gov on November 18, 2008

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00151697

Study ID Number: LTC 297-161104

ClinicalTrials.gov Identifier: NCT00151697

Health Authority: Netherlands: Dutch Health Care Inspectorate