Metformin

StudyPopulationInterventionOutcomesResultsCommentsDesignEL
Hamilton et al, 200328427 young people with type 1 diabetes
Aged 12–17 years
Canada
Metformin
versus
placebo 3 months
  1. HbA1c (change from baseline)
  2. Fasting glucose levels (change from baseline)
  3. BMI (change from baseline)
  4. Mild hypoglycaemic
  5. Severe hypoglycaemic episodes
  6. Gastrointestinal discomfort
  1. HbA1c (change from baseline) mean ± SD: −0.3 ± 0.7% vs. 0.3 ± 0.7% (p = 0.03)
  2. Fasting glucose levels (change from baseline): −0.9 ± 3.8 vs. −0.5 ± 3.2 mmol/l (p = 0.04)
  3. BMI (change from baseline): −0.05 ± 1.0 vs. 0.2 ± 0.5 kg/m2 (p = 0.35)
  4. Mild hypoglycaemic: 1.75 ± 0.8 vs. 0.9 ± 0.4 events/patient/week (p = 0.03)
  5. Severe hypoglycaemic episodes: 2/14 vs. 1/13
  6. Gastrointestinal discomfort: 6/11 vs. 5/13
Additional patient withdrew due to vomiting in metformin groupRCT crossoverIb
Särnbald et al, 200328526 young people with type 1 diabetes
Aged 16–20 years
Sweden
Metformin
versus
placebo 3 months
HbA1c (change from baseline)Change in HbA1c, −0.9%, 95% CI −1.6 to −0.1, p < 0.05 vs. 0.3%, p > 0.052 young people were excluded due to non-adherence to treatment protocol, both from intervention group, one of these had nauseaRCT crossoverIb
Gin, 198528610 patients with type 1 diabetes
Aged 40.8 ± 4 years
France
Randomised to a treatment for 1 week then a wash-out interval of 10 days before swapping to the next treatment, insulin therapy remained constant, patients were placed on an artificial pancreas for a euglycaemic hyperinsulinaemic clamp
Metformin 850 mg twice daily
versus
placebo
  1. Glucose infusion rate by artificial pancreas for a euglycaemic hyperinsulinaemic clamp
  2. Lactate, total cholesterol, triglycerides
  1. The mean value of glucose infusion increased with metformin: with metformin 3.71 ± 1.06 vs. without 3.4 ± 1.06 mg/kg/min, p < 0.001. This was not found in three patients
  2. Changes in other plasma values were not significant: lactate (1 ± 0.07 vs. 1.1 ± 0.06 mmol/l), total cholesterol (4.7 ± 0.20 vs. 4.7 ± 0.25 mmol/l), and triglycerides (1.18 ± 0.15 vs. 1.15 ± 0.10 mmol/l)
No description of how randomisation took placeRCT crossoverIb
Coscelli et al, 198428815 patients with type 1 diabetes
Italy
3 days on insulin alone, 5 days on treatment metformin 850 mg twice daily, then 2 days on insulin aloneGroup A (10 patients): diurnal plasma glucose profile, the difference between maximum and minimum glucose level and glycaemic control index
Group B (5 patients): fasting blood glucose level
Group A: significant difference in diurnal glycaemic profile at 2/7 time points (at 13:00 insulin alone 13.4 ± 1.1 vs. insulin and metformin 8.8 ± 1.0, p < 0.01, and at 18.00 insulin alone 10.7 ± 1.3 vs. insulin and metformin 7.9 ± 1.2 mmol/l, p < 0.01)
Group A: significant difference in the difference between maximum and minimum glucose level (insulin alone 10.1 ± 1.5 vs. insulin and metformin 6.8 ± 1.5 mmol/l, p<0.01)
Group A: significant improvement in the glycaemic control index with metformin (insulin alone 10.1 ± 1.5 vs. insulin and metformin 6.8 ± 1.5, p < 0.01)
Group B: significant decrease of glucose levels when metformin added (values not given as shown in graph)
Non-randomised and not controlled
Unknown how glycaemic control index was measured
Non-controlled intervention studyIIb
Janssen and Rillaerts, 199129012 patients with type 1 diabetes
Belgium
All patients were given 850 mg metformin twice a day for a 6-week periodHbA1c
Fasting glycaemia
Total cholesterol, HDL cholesterol and triglycerides
No significant differences in any of the measures after 6 weeks of metformin treatment.
HbA1c: start 9.5 ± 2.3% vs. metformin 9.1 ± 2.0%
Fasting glycaemia: start 205 ± 83 vs. metformin 185 ± 75 mg %
Total cholesterol: start 187.3 ± 39.5 vs. metformin 185.5 ± 38.0 mg/dl
HDL cholesterol: start 55.9 ± 12.6 vs. metformin 53.4 ± 11.5 mg/dl
Triglycerides: start 80.3 ± 63.6 vs. metformin 82.3 ± 29.9 mg/dl
Non-randomised and not controlled
Unknown age
Non-controlled intervention studyIIb
Pagano et al, 198328714 patients with type 1 diabetes
Aged under 60 years
Italy
After initial control period patients were given one treatment for 4–6 weeks then swapped over to the other treatment
Metformin 850 mg 3 times a daily before main meals.
versus
placebo
  1. Test period at end of treatment: an artificial pancreas control was administered and plasma glucose measured
  2. Adverse effects
  1. Mean plasma glucose values were statistically significantly lower after metformin administration than placebo (placebo 5.88 ± 0.18 vs. metformin 5.25 ± 0.20 mmol/l)
  2. No significant differences were found in the measurements of total cholesterol (placebo 4.7 ± 0.25 vs. metformin 4.7 ± 0.26 mmol/l), HDL cholesterol (placebo 1.15 ± 0.07 vs. metformin 1.26 ± 0.6 mmol/l) or triglycerides (placebo 1.14 ± 0.10 vs. metformin 1.18 ± 0.15 mmol/l)
  3. Transient abdominal pain and nausea was noted for the first week of metformin treatment
Unknown if the study was randomisedCrossover controlled trialIIa
Gómez et al, 200228910 young people and young adults with type 1 diabetes
Aged 19.1 ± 3.4 (range 14–45 years)
USA
After a 3-month run-in period, treatment of metformin 250 mg 2 times a day for week 1 was given. Increasing dosage up to 2500 mg was given every week if no change in blood glucose level or intestinal upset was reportedHbA1cNo statistical change in HbA1c, (start 10.94 ± 0.6% vs. metformin 10.39 ± 1.39%)Non-randomised and not controlledNon-controlled intervention studyIIb

From: Evidence tables

Cover of Type 1 Diabetes
Type 1 Diabetes: Diagnosis and Management of Type 1 Diabetes in Children and Young People.
NICE Clinical Guidelines, No. 15.2.
National Collaborating Centre for Women's and Children's Health (UK).
London: RCOG Press; 2004 Sep.
Copyright © 2004, National Collaborating Centre for Women’s and Children’s Health.

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