Hamilton 2003.

Methods	DESIGN: Randomized double blind placebo controlled trial COUNTRY: Canada DURATION OF INTERVENTION: 3 months DURATION OF FOLLOW‐UP: 3 months RUN‐IN PERIOD: 2 months LANGUAGE OF PUBLICATION: English
Participants	WHO PARTCIPATED: N= 27 adolescents SEX: 14 females, 13 males DISEASE: poorly controlled type 1 diabetes INCLUSION CRITERIA: AGE: 12‐17 years, PUBERTY: Tanner stage 2‐5, DURATION of DIABETES: > 3 years, METABOLIC CONTROL: HB A1c above 8% but <11% for the prior 6 months, daily dosage of insulin > 1 U/kg EXCLUSION CRITERIA: persistent nephropathy, proliferative retinopathy, recurrent ketoacidosis, recurrent severe hypoglycaemia, renal or hepatic dysfunction, another serious medical illness, known eating disorder, sexually active female unwilling to take birth control DIAGNOSTIC CRITERIA: Caucasians, typical diabetes symptoms and ketosis at onset, required insulin treatment from onset of diabetes SUBGROUPS: none CO‐MORBIDITIES: none CO‐MEDICATIONS: none
Interventions	NUMBER OF STUDY CENTRES: one COUNTRY/ LOCATION: Canada, Toronto SETTING: Diabetes clinic at The Hospital for Sick Children INTERVENTION N= 14 patients SEX: 8 females, 6 males DESCRIPTION: s.c. insulin and oral metformin 500 mg/d for 1 week, which was increased by 500 mg/day each week to a maximum of 1000 mg/day (500 mg twice daily) for those weighing less than 50 kg, 1500 mg/day (one 1000 mg and one 500 mg dose) for those weighing 50 to 75 kg, or 2000 mg/day (1000 mg twice daily for those weighing more 75 kg CONTROL N= 14 patients, SEX: 10 females, 4 males DESCRIPTION: s.c. insulin and placebo TREATMENT BEFORE STUDY: s.c. insulin TITRATION PERIOD: none
Outcomes	No subdivision into primary and secondary outcomes. Outcomes were measured on inclusion and at the end of the study 1. Glycemic control: HBA1c and fasting blood glucose 2. Side effects: hypoglycaemia, GIT (discomfort, vomiting) 3. Quality of life: not reported 4. Insulin dose: daily insulin dose/Kg 5. Weight: BMI, body weight 6. Serum lipids: serum triglycerides and cholesterol 7. Insulin sensitivity (by the frequently sampled intravenous glucose tolerance test [FSIGT]) 8. Cost: not reported 9. Compliance : <25% of prescribed pills returned 10. Mortality: not reported 11. Morbidity: not reported SAFETY ASSESSMENTS: 1. renal functions 2. hepatic functions (alanine aminotransferase and aspartate aminotransferase) 3. complete blood count 4. lactate 5. mild symptomatic hypoglycemia 6. severe hypoglycemic episodes
Notes	Sponsor: grants from the Hospital for Sick Children Research Institute and the Order of the Eastern Star of Ontario. Drug and Placebo were provided by Aventis Pharma Author contacted: did not respond to date about missing data Study retreived:Medline
Risk of bias
Bias	Authors' judgement	Support for judgement
Allocation concealment?	Low risk	A ‐ Adequate