Table 5.
Adjusted hazard ratios (95% CI) for each study outcome* compared with metformin monotherapy
| Study outcome | |||||
|---|---|---|---|---|---|
| Blindness | Hyperglycaemia | Hypoglycaemia | Amputation | Kidney failure | |
| Monotherapy | |||||
| Metformin alone | 1.00 | 1.00 | 1.00 | 1.00 | 1.00 |
| Sulphonylureas alone | 1.42 (1.25 to 1.62) | 1.38 (1.25 to 1.52) | 7.32 (6.55 to 8.18) | 1.44 (1.20 to 1.71) | 2.63 (2.25 to 3.06) |
| Insulin alone | 1.96 (1.50 to 2.55) | 2.48 (2.11 to 2.92) | 21.17 (18.48 to 24.25) | 2.68 (2.08 to 3.46) | 2.88 (2.32 to 3.57) |
| Glitazones alone | 0.98 (0.31 to 3.03) | 1.50 (0.78 to 2.89) | 1.83 (0.59 to 5.70) | 1.88 (0.60 to 5.84) | 2.55 (1.13 to 5.74) |
| Gliptins alone | 1.39 (0.66 to 2.93) | 1.44 (0.85 to 2.43) | 0.83 (0.21 to 3.33) | 1.03 (0.33 to 3.20) | 3.52 (2.04 to 6.07) |
| Other hypoglycaemic agents alone | 0.82 (0.26 to 2.55) | 0.32 (0.08 to 1.29) | 6.44 (3.63 to 11.42) | — | 1.17 (0.63 to 2.18) |
| Dual therapy | |||||
| Metformin and sulphonylureas | 0.94 (0.85 to 1.04) | 1.02 (0.95 to 1.09) | 6.03 (5.47 to 6.63) | 1.08 (0.95 to 1.23) | 0.76 (0.62 to 0.92) |
| Metformin and insulin | 1.58 (1.21 to 2.07) | 1.95 (1.63 to 2.34) | 14.34 (12.40 to 16.59) | 1.78 (1.34 to 2.37) | 1.13 (0.65 to 1.98) |
| Metformin and glitazones | 0.87 (0.58 to 1.29) | 0.60 (0.45 to 0.80) | 1.35 (0.89 to 2.05) | 0.57 (0.30 to 1.06) | 0.71 (0.33 to 1.50) |
| Metformin and gliptins | 0.72 (0.49 to 1.04) | 0.78 (0.62 to 0.97) | 1.23 (0.84 to 1.80) | 0.84 (0.55 to 1.30) | 0.59 (0.28 to 1.25) |
| Metformin and other hypoglycaemic agents | 0.83 (0.50 to 1.38) | 1.06 (0.79 to 1.41) | 2.77 (1.92 to 4.01) | 0.93 (0.51 to 1.70) | 0.57 (0.18 to 1.79) |
| Sulphonylureas and insulin | 2.13 (1.47 to 3.09) | 2.62 (1.89 to 3.63) | 23.91 (19.89 to 28.75) | 2.15 (1.40 to 3.29) | 3.56 (2.64 to 4.82) |
| Sulphonylureas and glitazones | 0.80 (0.38 to 1.69) | 1.93 (1.21 to 3.07) | 13.22 (10.04 to 17.39) | 2.06 (1.13 to 3.76) | 2.14 (1.27 to 3.61) |
| Sulphonylureas and gliptins | 1.32 (0.78 to 2.25) | 0.98 (0.57 to 1.69) | 5.93 (4.12 to 8.53) | 1.30 (0.69 to 2.45) | 3.21 (2.08 to 4.93) |
| Sulphonylureas and other hypoglycaemic agents | 0.69 (0.17 to 2.76) | 0.73 (0.24 to 2.27) | 12.12 (7.57 to 19.41) | 2.02 (0.75 to 5.43) | 2.38 (1.11 to 5.09) |
| Triple therapy | |||||
| Metformin, sulphonylureas, and insulin | 1.36 (0.97 to 1.89) | 1.46 (1.12 to 1.91) | 13.17 (11.14 to 15.57) | 1.30 (0.88 to 1.91) | 1.06 (0.53 to 2.16) |
| Metformin, sulphonylureas, and glitazones | 0.67 (0.48 to 0.94) | 0.99 (0.79 to 1.25) | 6.32 (5.35 to 7.45) | 0.70 (0.47 to 1.05) | 1.21 (0.75 to 1.96) |
| Metformin, sulphonylureas and gliptins | 0.82 (0.62 to 1.08) | 1.09 (0.91 to 1.32) | 5.07 (4.28 to 6.00) | 0.99 (0.73 to 1.33) | 0.68 (0.39 to 1.20) |
| Metformin, sulphonylureas and other hypoglycaemic agents | 0.91 (0.59 to 1.43) | 1.03 (0.76 to 1.38) | 4.31 (3.26 to 5.68) | 0.85 (0.50 to 1.45) | 0.93 (0.38 to 2.26) |
| All other drug combinations | 0.94 (0.64 to 1.39) | 1.43 (1.14 to 1.80) | 9.02 (7.50 to 10.83) | 1.25 (0.86 to 1.82) | 1.60 (0.98 to 2.62) |
| No medication | 1.40 (1.29 to 1.52) | 1.58 (1.51 to 1.65) | 3.06 (2.77 to 3.37) | 1.44 (1.28 to 1.62) | 1.85 (1.61 to 2.12) |
Treatment categories are mutually exclusive.
*Hazard ratios adjusted for sex; age; duration since diagnosis of diabetes (five levels); ethnicity (nine levels); Townsend deprivation score; smoking status (five levels); use of anticoagulants, thiazides, ACE inhibitors, angiotensin 2 blockers, calcium channel blockers, statins, aspirin; existing complications (blindness, hyperglycaemic coma, hypoglycaemia, amputation, severe kidney failure); hypertension; cardiovascular disease; atrial fibrillation; chronic renal disease; rheumatoid arthritis; valvular heart disease; peripheral vascular disease; body mass index; systolic blood pressure; HbA1c; serum creatinine; and cholesterol:high density lipoprotein ratio.