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

December 5, 2008 updated by: Steno Diabetes Center Copenhagen

Effect of Metformin On Glycaemic Control and Non-Glycaemic Cardiovascular Risk-Factors in Patients With Type-1 Diabetes, With Long-Standing Inadequate Glycaemic Control by Insulin and Diet

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Actual)

100

Phase

  • Phase 4

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Placebo Comparator: 1
Single-blind placebo run-in period. Duration one month.
Drug: Placebo.
Tablet Placebo (corresponding to 500 mg metformin). Dosage: 1 tablet per day.
Drug: Placebo.
Tablet Placebo (corresponding to 500 mg metformin). Dosage: 2 tablets two times daily.
Active Comparator: 2
Metformin 2000 mg, double-masked randomized during 12 months.
Drug: Metformin
Tablet Metformin 500 mg, Dosage: 1000 mg two times daily (2000 mg total daily dose).
Placebo Comparator: 3
Placebo, double-masked randomized during 12 months.
Drug: Placebo.
Tablet Placebo (corresponding to 500 mg metformin). Dosage: 1 tablet per day.
Drug: Placebo.
Tablet Placebo (corresponding to 500 mg metformin). Dosage: 2 tablets two times daily.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
HbA1c - difference between final visit and baseline.

Secondary Outcome Measures

Outcome Measure
Insulin-dose
Absolute HbA1c
Number of mild and severe hypoglycaemia with or without measurements of blood-glucose.
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.
Plasma-fibrinogen
Serum-albumin
Markers of endothelial dysfunction: Von Willebrand Factor, ICAM, VCAM, Amadori-protein, selectin and endothelin.
Plasma-homocysteine
Asymmetric DiMethylArginine - ADMA
Urine-albumin-excretion in three 24 hour urine-collections
Blood-pressure in the sitting position after 10 minutes of rest.
Fasting lipid-profile (total-cholesterol, LDL-cholesterol, HDL-cholesterol, VLDL-cholesterol and triglycerides), small-dense-LDL, Lp(a) and Apo-B100.
Weight, BMI and Waist-hip-ratio
White blood-cell-count, hs-CRP, Interleukin-6 and TNF-alfa.
Serum-creatinine, sodium, potassium, ASAT, alkaline phosphatase, Factor 2, 7, 10, Cobalamin, Erythrocyte-folate and Haemoglobin-concentration.
Extra blood- and urine-samples will be stored at -80 degrees Celsius for potential extra analyses after closure of the study. DNA will be stored for later pharmaco-genetic analysis.

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Steno Diabetes Center Copenhagen

Investigators

  • Study Chair: Allan A Vaag, M.D., chief physician, Steno Diabetes Center Copenhagen

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

December 1, 2003

Primary Completion (Actual)

August 1, 2006

Study Completion (Actual)

August 1, 2006

Study Registration Dates

First Submitted

July 1, 2005

First Submitted That Met QC Criteria

July 1, 2005

First Posted (Estimate)

July 12, 2005

Study Record Updates

Last Update Posted (Estimate)

December 8, 2008

Last Update Submitted That Met QC Criteria

December 5, 2008

Last Verified

December 1, 2008

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • Type-1-Metformin

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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