Clinical trial NCT00151697: LANN-study: Lantus, Amaryl, Novorapid, Novomix Study
Official title: New Approach to Treat Type II Diabetes Failing on Maximal Oral Treatment
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Diabetes Mellitus Type II
Keywords: diabetes
failing oral treatment
weight gain
Lead sponsor: Rijnstate Hospital
Sponsor class: OTHER
First posted: 2005-09-09
Enrollment: 150
Sex: ALL
Minimum age (years): 30
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.

Detailed description: 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.

Eligibility criteria: 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.

Primary outcomes:
measure: glycemic control based on HbA1c
measure: Body weight
Secondary outcomes:
measure: 8-point glucose day curve of three consecutive days
measure: 24-hour glycemic control measured by continuous glucose monitoring for three consecutive days
measure: recorded number of hypoglycemic events per month
measure: waist circumference
measure: dexa measurements of body composition
measure: plasma lipid levels
measure: basal and stimulated C-peptide levels
measure: adverse effects
Other outcomes:
Locations:
city: Arnhem
country: Netherlands
facility: Rijnstate Hospital
Study officials:
affiliation: Rijnstate Hospital
name: Hans de Boer, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: de Boer H, Jansen M, Koerts J, Verschoor L. Prevention of weight gain in type 2 diabetes requiring insulin treatment. Diabetes Obes Metab. 2004 Mar;6(2):114-9. doi: 10.1111/j.1463-1326.2004.00322.x.