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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00118937
Recruitment Status : Completed
First Posted : July 12, 2005
Last Update Posted : December 8, 2008
Information provided by:
Steno Diabetes Center Copenhagen

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.


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.

Condition or disease Intervention/treatment Phase
Diabetes Mellitus, Type 1 Drug: Metformin Drug: Placebo. Phase 4

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 100 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: 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
Study Start Date : December 2003
Actual Primary Completion Date : August 2006
Actual Study Completion Date : August 2006

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Diabetes Type 1

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.

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: 2 tablets two times daily.

Primary Outcome Measures :
  1. HbA1c - difference between final visit and baseline.

Secondary Outcome Measures :
  1. Absolute HbA1c
  2. Number of mild and severe hypoglycaemia with or without measurements of blood-glucose.
  3. Insulin-dose
  4. The following parameters are measured at baseline and at the final visit after 12 months of intervention:
  5. Plasma-PAI-antigen and -activity, t-PA-antigen- and activity.
  6. Plasma-fibrinogen
  7. Serum-albumin
  8. Markers of endothelial dysfunction: Von Willebrand Factor, ICAM, VCAM, Amadori-protein, selectin and endothelin.
  9. Plasma-homocysteine
  10. Asymmetric DiMethylArginine - ADMA
  11. Urine-albumin-excretion in three 24 hour urine-collections
  12. Blood-pressure in the sitting position after 10 minutes of rest.
  13. Fasting lipid-profile (total-cholesterol, LDL-cholesterol, HDL-cholesterol, VLDL-cholesterol and triglycerides), small-dense-LDL, Lp(a) and Apo-B100.
  14. Weight, BMI and Waist-hip-ratio
  15. White blood-cell-count, hs-CRP, Interleukin-6 and TNF-alfa.
  16. Serum-creatinine, sodium, potassium, ASAT, alkaline phosphatase, Factor 2, 7, 10, Cobalamin, Erythrocyte-folate and Haemoglobin-concentration.
  17. 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.

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT00118937

Sponsors and Collaborators
Steno Diabetes Center Copenhagen
Layout table for investigator information
Study Chair: Allan A Vaag, M.D., chief physician Steno Diabetes Center Copenhagen
Principal Investigator: Soeren S Lund, M. D. Steno Diabetes Center Copenhagen
Publications automatically indexed to this study by Identifier (NCT Number):
Layout table for additonal information Identifier: NCT00118937    
Other Study ID Numbers: Type-1-Metformin
First Posted: July 12, 2005    Key Record Dates
Last Update Posted: December 8, 2008
Last Verified: December 2008
Additional relevant MeSH terms:
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Diabetes Mellitus
Diabetes Mellitus, Type 1
Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System Diseases
Autoimmune Diseases
Immune System Diseases
Hypoglycemic Agents
Physiological Effects of Drugs