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. 2016 Jul 13;354:i3477. doi: 10.1136/bmj.i3477

Table 6.

Adjusted hazard ratios (95% confidence intervals) for each outcome (model F) compared with monotherapy with metformin

Treatments Adjusted hazard ratio (95% CI)
Heart failure Cardiovascular disease All cause mortality
Metformin (reference) 1.00 1.00 1.00
Monotherapy or no treatment:
No current treatment 1.47 (1.40 to 1.53)* 1.31 (1.27 to 1.35)* 1.55 (1.52 to 1.59)*
Sulphonylureas 1.47 (1.37 to 1.57)* 1.31 (1.24 to 1.38)* 1.93 (1.87 to 2.00)*
Insulin 1.85 (1.61 to 2.12)* 1.59 (1.41 to 1.80)* 2.55 (2.41 to 2.71)*
Glitazones 0.74 (0.38 to 1.42)† 1.03 (0.69 to 1.54)† 1.38 (1.04 to 1.83)†
Gliptins 1.28 (0.85 to 1.92)† 1.50 (1.11 to 2.02)* 1.86 (1.55 to 2.25)*
Other diabetes drugs 1.35 (0.85 to 2.14)† 1.47 (1.03 to 2.09)* 1.65 (1.31 to 2.08)*
Dual treatment:
Metformin and sulphonylureas 1.09 (1.03 to 1.15)* 0.99 (0.95 to 1.03)† 0.96 (0.93 to 0.99)†
Metformin and insulin 1.58 (1.36 to 1.83)* 1.16 (1.03 to 1.32)* 1.18 (1.07 to 1.31)*
Metformin and glitazones 0.74 (0.58 to 0.93)‡ 0.60 (0.51 to 0.70)‡ 0.86 (0.74 to 1.00)†
Metformin and gliptins 0.91 (0.76 to 1.10)† 0.87 (0.77 to 0.99)‡ 0.80 (0.71 to 0.91)‡
Metformin and other hypo 1.08 (0.84 to 1.40)† 0.96 (0.80 to 1.15)† 0.72 (0.58 to 0.89)‡
Sulphonylureas and insulin 1.73 (1.41 to 2.13)* 1.54 (1.26 to 1.88)* 2.32 (2.09 to 2.58)*
Sulphonylureas and glitazones 0.95 (0.68 to 1.31)† 0.99 (0.76 to 1.28)† 1.50 (1.24 to 1.80)*
Sulphonylureas and gliptins 1.29 (0.96 to 1.72)† 1.27 (1.00 to 1.60)† 1.44 (1.23 to 1.68)*
Sulphonylureas and other diabetes drugs 2.13 (1.39 to 3.28)* 1.33 (0.87 to 2.03)† 2.07 (1.55 to 2.77)*
Triple treatment:
Metformin, sulphonylureas, and insulin 1.34 (1.11 to 1.60)* 1.24 (1.08 to 1.42)* 1.53 (1.35 to 1.72)*
Metformin, sulphonylureas, and glitazones 0.79 (0.66 to 0.93)‡ 0.78 (0.70 to 0.87)‡ 0.68 (0.59 to 0.78)‡
Metformin, sulphonylureas, and gliptins 0.89 (0.76 to 1.03)† 0.92 (0.83 to 1.02)† 0.76 (0.69 to 0.85)‡
Metformin, sulphonylureas, and other diabetes drugs 0.87 (0.68 to 1.13)† 0.81 (0.68 to 0.97)‡ 0.71 (0.58 to 0.88)‡
All other drug combinations 1.06 (0.86 to 1.29)† 1.07 (0.94 to 1.23)† 1.05 (0.91 to 1.22)†

*Significantly increased.

†Non-significant.

‡Significantly decreased.

Hazard ratios adjusted for: sex; age; calendar year; duration since diagnosis of diabetes (five levels); ethnicity (nine levels); Townsend deprivation score; smoking status (five levels); use of other diabetes drugs, anticoagulant thiazides, angiotensin coverting enzyme inhibitors, angiotensin receptor blockers, calcium channel blockers, statins, and aspirin; previous complications (blindness, hyperglycaemia, 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; haemoglobin A1c; serum creatinine level; cholesterol to high density lipoprotein cholesterol ratio.