| Trial | Sulfonylurea intervention | Metformin intervention | Plan in case of treatment failure | Intervention arm not included in this analysis |
|---|---|---|---|---|
| ADOPT, 2006 (20)– (26) | Glibenclamide, PO; 2.5 mg/d initially, then up to 15 mg/d (7.5 mg twice daily) | Metformin, PO; 500 mg/d initially, then up to 2 g/d (1 g twice daily) | Escape medicine not allowed; participants excluded | Rosiglitazone |
| Campbell et al., 1994 (27) | Glipizide, PO; 5 mg/d initially, increased to a maximum divided dose of 15 mg/d | Metformin, PO; 500 mg/d initially, increased by 500 mg/d at each visit (every second week) to maximum of 3 g/d | NR | |
| Collier et al., 1989 (28) | Gliclazide, PO; 80–240 mg/d | Metformin, PO; 1.5–3.0 g/d | NR | Healthy controls |
| DeFronzo et al., 1995 (29) | Glibenclamide, PO; 5 mg twice daily for first week, then 10 mg twice daily. Metformin placebo | Metformin, PO; 500 mg/d initially. After 1 wk, increased to 1 g/d by adding 500-mg tablet at breakfast. After 2 wk, increased to 1.5 g/d by adding 500-mg tablet at lunch. After 3 wk, increased to 2 g/d by adding a second 500-mg tablet at evening meal. After 4 wk, increased to 2.5 g/d by adding a second 500-mg tablet at breakfast. Glibenclamide placebo | Escape medicine not allowed; participants excluded | Combination of metformin plus glibenclamide |
| Derosa et al., 2004 (42) | Glimepiride, PO; 1 mg/d initially, titrated to maximum of 4 mg/d (2 mg twice daily) | Metformin, PO; 1 g/d initially, titrated to maximum of 3 g/d (1 g 3 times daily) | Escape medicine allowed | |
| Hermann et al., 1991a (30) | Glibenclamide, PO; 1.75–10.5 mg/d | Metformin, PO; 0.5–3 g/d | NR | |
| Hermann et al., 1991b (31)– (34) | Glibenclamide, PO; 3.5 mg/d initially, increased to 14 mg/d. Tablets given shortly before breakfast; if daily dose exceeded 7 mg, then divided between breakfast and evening meal. Metformin placebo. | Metformin, PO; 1 g/d initially, increased to 1–3 g/d in 2 doses shortly before breakfast and evening meal. Glibenclamide placebo. | Escape medicine allowed | Combination of metformin plus glibenclamide |
| Kamel et al., 1997 (35) | Gliclazide and glibenclamide | Metformin | NR | Acarbose and placebo |
| Lawrence et al., 2004 (36) | Gliclazide, PO; 80 mg/d in single dose, titrated to 160 mg/d depending on fasting blood glucose level | Metformin, PO; 500 mg twice daily, titrated to 1 g 3 times daily depending on fasting blood glucose level | Escape medicine not allowed; participants excluded | Pioglitazone |
| Tang et al., 2004 (41) | Glimepiride, PO; 1–2 mg/d | Metformin, PO; 750–1500 mg/d | NR | |
| Tessier et al., 1999 (37) | Gliclazide, PO; titrated to glycemic target; doses were 80, 160, 240 and 320 mg/d divided into 2 doses with breakfast and evening meal | Metformin, PO; titrated to glycemic target; doses were 750, 1500 and 2250 mg/d divided into 3 doses with each meal | NR | |
| Tosi et al., 2003 (38) | Glibenclamide, PO; starting dose was 1 tablet (5 mg) before lunch. Increased to 1 tablet twice daily (before breakfast and dinner), 2 tablets twice daily (before breakfast and dinner), and 2 tablets 3 times daily (before breakfast, lunch and dinner). For those given glibenclamide alone, the last 2 steps were 1 tablet of active drug + 1 tablet of placebo | Metformin, PO; starting dose was 1 tablet (500 mg) before lunch. Increased to 1 tablet twice daily (before breakfast and dinner), 2 tablets twice daily (before breakfast and dinner), and 2 tablets 3 times daily (before breakfast, lunch and dinner). Therefore, scheduled dose steps were 0.5, 1, 2 and 3 g/d for metformin | Escape medicine not allowed; participants excluded | Combination of metformin plus glibenclamide |
| UKPDS 34, 1998 (2), (39), (40) | Glibenclamide, PO; 2.5–20 mg/d | Metformin, PO; 850-mg tablet daily initially, increased to 850 mg twice daily, then 1700 mg in the morning and 850 mg with evening meal (maximum 2550 mg/d). If symptoms of diarrhea or nausea occurred, dose reduced to level that previously did not cause symptoms | Escape medicine allowed | Chlorpropamide and insulin |
| Yamanouchi et al., 2005 (43) | Glimepiride, PO; 1–2 mg/d | Metformin, PO; 750 mg/d | Escape medicine allowed | Pioglitazone |
Note: ADOPT = A Diabetes Outcome Progression Trial, NR = not reported, po = oral dose, UKPDS = United Kingdom Prospective Diabetes Study.