Effect of Metformin in Patients With Type-1 Diabetes With Inadequate Glycaemic Control by Insulin and Diet

NCT ID: NCT00118937

Last Updated: 2008-12-08

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE4
• Total Enrollment: 100 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2003-12-31
• Study Completion Date: 2006-08-31

Brief Summary

Ninety percent of patients with type-1-diabetes will develop late-diabetic complications in the eyes, kidneys, nervous- or cardiovascular-system. Poor glycaemic control is an important risk-factor for development of these late-diabetic complications. The Diabetes Control and Complications Trial (DCCT)-study showed, that improved glycaemic control can prevent the development and progression of these late-diabetic complications. Until now treatment with insulin- and diet-therapy has been the only treatment-modalities available to improve the glycaemic control in patients with type-1-diabetes. A substantial number of these patients still have long-standing poor glycaemic control despite intensive treatment with insulin- and diet-therapy.

The antidiabetic drug metformin has shown to be able to improve the glycaemic control in combination with insulin and furthermore reduce both mortality and the risk of developing cardiovascular disease in patients with type-2-diabetes.

Only few small studies have investigated the effect of treatment with metformin in patients with type-1-diabetes. These studies have suggested a positive effect of metformin in these patients too.

Method:

100 patients with type-1-diabetes with persistent poor glycaemic control i.e. HbA1c > 8.5% during the last 12 months are eligible. Patients are treated for one month with placebo. Hereafter half of the patients will be treated with metformin and the other half continues with placebo for 12 months both as add-on therapy. All patients are continuing ongoing treatment with insulin throughout the study. Before and after the start of treatment with metformin the effect on glycaemic control and other known risk-factors for development of cardiovascular disease i. e. blood-pressure, fasting lipids, urine-albumine-excretion, endothelial dysfunction, inflammation, fibrinolysis etc. is assessed.

This study will show if treatment with metformin can improve the glycaemic control and hereby the prognosis of patients with type-1-diabetes with persistent poor glycaemic control despite intensive treatment with insulin- and diet-therapy. This group of patients suffers the highest risk of developing late-diabetic complications with reduced quality of life and life-expectancy as a consequence.

Conditions

Diabetes Mellitus, Type 1

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

1

Single-blind placebo run-in period. Duration one month.

Group Type: PLACEBO_COMPARATOR

Placebo.

Intervention Type: DRUG

Tablet Placebo (corresponding to 500 mg metformin). Dosage: 1 tablet per day.

2

Metformin 2000 mg, double-masked randomized during 12 months.

Group Type: ACTIVE_COMPARATOR

Metformin

Intervention Type: DRUG

Tablet Metformin 500 mg, Dosage: 1000 mg two times daily (2000 mg total daily dose).

3

Placebo, double-masked randomized during 12 months.

Group Type: PLACEBO_COMPARATOR

Placebo.

Intervention Type: DRUG

Tablet Placebo (corresponding to 500 mg metformin). Dosage: 2 tablets two times daily.

Interventions

Metformin

Tablet Metformin 500 mg, Dosage: 1000 mg two times daily (2000 mg total daily dose).

Intervention Type: DRUG

Placebo.

Tablet Placebo (corresponding to 500 mg metformin). Dosage: 1 tablet per day.

Intervention Type: DRUG

Placebo.

Tablet Placebo (corresponding to 500 mg metformin). Dosage: 2 tablets two times daily.

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• HbA1c > 8.5% for more than one year prior to enrolment.
• Diabetes-duration > 5 years.
• Age at onset of diabetes < 35 years
• Fasting C-peptide < 300 pmol/l
• Age > 18 years at enrolment.

Exclusion Criteria

• Clinical or biochemical signs of kidney-, liver- or heart-failure.
• Other coexisting serious morbidity, which will affect the study-participation or outcome of the study i.e. cancer.
• Known abuse of any medication or alcohol
• Hypoglycaemia unawareness.
• Pregnancy or planned pregnancy in the study-period.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Steno Diabetes Center Copenhagen

OTHER

Sponsor Role: lead

Principal Investigators

Allan A Vaag, M.D., chief physician

Role: STUDY_CHAIR

Steno Diabetes Center Copenhagen

Soeren S Lund, M. D.

Role: PRINCIPAL_INVESTIGATOR

Steno Diabetes Center Copenhagen

References

Lund SS, Tarnow L, Astrup AS, Hovind P, Jacobsen PK, Alibegovic AC, Parving I, Pietraszek L, Frandsen M, Rossing P, Parving HH, Vaag AA. Effect of adjunct metformin treatment in patients with type-1 diabetes and persistent inadequate glycaemic control. A randomized study. PLoS One. 2008;3(10):e3363. doi: 10.1371/journal.pone.0003363. Epub 2008 Oct 9.

Reference Type: DERIVED

PMID: 18852875 (View on PubMed)

Other Identifiers

Type-1-Metformin

Identifier Type: -

Identifier Source: org_study_id