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

NCT00118937 | Completed Phase 4

• 1 other identifier: Type-1-Metformin
• Study Type: interventional
• Target: 100
• Locations: 0 countries
• Sites: N/A

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

Outcome Measures

Primary Outcomes (1)

• HbA1c - difference between final visit and baseline.

Secondary Outcomes (17)

• Absolute HbA1c

• Number of mild and severe hypoglycaemia with or without measurements of blood-glucose.

• Insulin-dose

• The following parameters are measured at baseline and at the final visit after 12 months of intervention:

• Plasma-PAI-antigen and -activity, t-PA-antigen- and activity.

Study Arms (3)

1

PLACEBO COMPARATOR

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

Drug: Placebo.

2

ACTIVE COMPARATOR

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

Drug: Metformin

3

PLACEBO COMPARATOR

Placebo, double-masked randomized during 12 months.

Drug: Placebo.

Interventions

Metformin DRUG

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

2

Placebo. DRUG

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

1

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Steno Diabetes Center Copenhagen: lead

Related Publications (1)

• 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.

  PMID: 18852875 DERIVED

MeSH Terms

Conditions

Diabetes Mellitus, Type 1

Interventions

Metformin

Condition Hierarchy (Ancestors)

Diabetes Mellitus; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases; Autoimmune Diseases; Immune System Diseases

Intervention Hierarchy (Ancestors)

Biguanides; Guanidines; Amidines; Organic Chemicals

Study Officials

• Allan A Vaag, M.D., chief physician

  Steno Diabetes Center Copenhagen

  STUDY CHAIR

• Soeren S Lund, M. D.

  Steno Diabetes Center Copenhagen

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER

Study Record Dates

• First Submitted: July 1, 2005
• First Posted: July 12, 2005
• Study Start: December 1, 2003
• Primary Completion: August 1, 2006
• Study Completion: August 1, 2006
• Last Updated: December 8, 2008

Record last verified: 2008-12