Table 1.
Baseline characteristics of included trials
| Trial | UKPDS33 | UKPDS34 | PROactive | ADVANCE | ACCORD | HEART2D | VADT | RECORD | BARI2D | ADDITION | SAVOR-TIMI53 | EXAMINE | DIGAMI1 | AleCardio | TECOS |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Intervention | Intensive policy with a sulphonylura or insulin vs conventional policy with diet | intensive blood-glucose control policy with metformin vs diet alone | Addition of pioglitazone or placebo to usual diabetes therapy | Intensive (glicazide plus other drugs) vs standard glucose control | Intensive therapy vs standard therapy | Prandial vs basal strategy | Intensive or standard glucose control | Addition of rosiglitazone or combination of metformin and sulfonylurea | Insulin sensitization vs insulin provision therapy | Routine vs intensive treatment of multiple risk factors | Addition of Saxagliptin vs placebo to usual diabetes therapy | Addition of Alogliptin vs placebo to usual diabetes therapy | Intensified insulin-based glycaemic control vs conventional glucose-lowering treatment | Aleglitazar 150 μg or placebo daily | Add sitagliptin or placebo to existing therapy |
| Publication year | 1998 | 1998 | 2005 | 2008 | 2008 | 2009 | 2009 | 2009 | 2009 | 2011 | 2013 | 2013 | 2014 | 2015 | 2015 |
| Location | 23 centers in England | 15 centers in England | 321 centers in 19 countriesa | 215 centers in 20 countriesb | 77 centers in USA | 105 centers in 17 countriesc | 20 centers in USA | 364 centers in 25 countriesd | 49 centers in 6 countriese | 334 practices in Denmark, Netherlands, and UK | 788 sites in 26 countriesf | 898 sites in 48 countriesg | 19 hospitals in Swedish | 720 hospitals in 26 countriesh | 673 sites in 38 countriesi |
| Study design | Randomized, Open label | Randomized, Open label | Randomized, Placebo-controlled | Factoria randomized trial | Randomized, 2 × 2 factorial design | Randomized, open label | Open label, permuted-block design | Randomized, open label | Randomized, 2by2 factorial design | Cluster-randomized, parallel-group trial | Randomized, double-blind, placebo-controlled | Randomized, double-blind | Randomized, open-label | Randomized, double blind, placebo controlled trial | Randomized, double blind, placebo controlled, event driven trial |
| Number of patients | 3867 | 1704 | 5238 | 11,140 | 10,251 | 1115 | 1791 | 4447 | 2368 | 3055 | 16,492 | 5380 | 1240 | 7226 | 14,671 |
| Duration of diabetes | Newly diagnosed | Newly diagnosed | 8 ± 6 | 8 ± 6† | 10 | 9 ± 7.2† | 11.5 ± 7.5† | 7 ± 4.8† | 10.4 ± 8.7 | Screened diabetes | 10.3 ± 2.8† | 7.2 ± 2.8† | 10.5 ± 5.4† | 8.6 ± 7.7 | 9.4 ± 2.6* |
| Population | Newly diagnosed T2DM | Newly diagnosed T2DM | T2DM with macrovascular disease | T2DM, history of macrovascular or microvascular disease or at least one other CV risk factor | T2DM with established CVD or additional CV risk factors | T2DM after acute MI | T2DM | T2DM | T2DM and heart disease | Screen detected T2DM | T2DM with history of CV event or at risk for | T2DM with ACS within 15–90 before randomization | T2DM and acute MI | Type 2 diabetes with hospitalized for ACS | Type 2 diabetes with established cardiovascular disease |
| Average follow up (years) | 10.1 | 10.7 | 2.9 | 5.0 | 3.5 | 2.6 | 5.6 | 5.5 | 5.3 | 5.3 | 2.1 | 18 months | 3.4 | 104 weeks | 3 |
| Age | 54 (48–60)* | 53 ± 8.6† | 62 ± 8 | 66 ± 6 | 62 ± 7 | 61 ± 9.7 | 60 ± 9 | 58 ± 8 | 62 ± 9 | 60 ± 6.8 | 65 ± 8.5 | 61 | 67.5 ± 9.4 | 61 ± 10 | 66.0 ± 8.0 |
| BMI (kg/m2) | 27.5 ± 5.2 | 31.7 ± 4.9† | 31 ± 5 | 28 ± 5 | 32 ± 6 | 29.1 ± 4.8† | 31 ± 4 | 31.5 ± 4.7† | 31.7 ± 6.0 | 31.6 ± 5.6 | 31.1 ± 5.6 | 28.7 ± 11.6 | 27.1 ± 4.3 | 28.6 ± 1.7 | 30.2 ± 5.7 |
| HbA1c at baseline (100 %) | 7.1 ± 1.5 | 7.2 ± 1.5† | 7.9 ± 1.4 | 7.5 ± 1.6 | 8.3 ± 1.1 | 8.3 ± 1.5 | 9.4 ± 2.0 | 7.9 ± 0.7 | 7.7 ± 1.6 | 7.0 ± 1.6 | 8.0 ± 1.4 | 8.0 ± 1.1 | 8.0 ± 1.9 | 7.8 ± 1.7† | 7.3 ± 0.7 |
| Intervention group | 7.0 ± 1.5* | 8.3 | 7.0 | 6.5 ± 0.99 | 6.4 ± 0.6 | 7.7 ± 0.1 | 6.9 ± 0.6* | 7.5 | 7.0 ± 1.2 | 6.6 ± 0.95 | 7.7 | 7.7 | 7.3 ± 1.9 | 7.03 | 7.1 |
| Conventional group | 7.9 ± 1.4* | 8.8 | 7.6 | 7.2 ± 1.4 | 7.5 ± 0.7 | 7.8 ± 0.1 | 8.4 ± 1.1* | 7.8 | 7.5 ± 1.4 | 6.7 ± 0.95 | 7.9 | 8.0 | 7.6 | 7.77 | 7.5 |
| Change in HbA1c‡ | 0.1 | −1.1 | 0.9 | 1.0 | 1.9 | 0.6 | 1.5 | 0.4 | 0.7 | 0.4 | 0.3 | 0.3 | 0.7 | 0.8 | 0.2 |
Data are presented as mean ± SD, or median (interquartile range), unless otherwise specified
T2DM type 2 diabetes mellitus, BMI body mass index, HbA1c glycosylated hemoglobin
aAustria, Belgium, Denmark, Estonia, Finland, Czeh Repulic, France, Germany, Hungary, Italy, Latvia, Lithuania, Netherlands, Norway, Poland, Siovakia, Sweden, Switzerland and UK
bAustria, Canada, China, Czeh Repulic, Estonia, France, Germany, Hungary, India, Ireland, Italy, Lithuania, Malaysia, Netherlands, New Zealand, Philippines, Poland, Russia, Slovakia, and UK
cCanada, Croatia, Czech Republic, Germany, Hungary, India, Israel, Lebanon, Poland, Romania, Russian Federation, Slovakia, Slovenia, South Africa, Spain, Turkey, and UK
dAustralia, Belgium, Bulgaria, Croatia, Czech Republic, Denmark, Estonia, Finland, France, Germany, Greece, Hungary, Italy, Latvia, Lithuania, Netherlands, New Zealand, Poland, Romania, Russia, Slovakia, Spain, Sweden, Ukraine, and UK
eA, Canada, Brazil, Mexico, the Czech Republic and Austria
fArgentina, Australia, Brazil, Canada, Chile, China, Czech Republic, France, Germany, Hong Kong, Hungary, India, Israel, Italy, Mexico, Netherlands, Peru, Poland, Russian Federation, South Africa, Spain, Sweden, Taiwan, Thailand, UK and USA
gArgentina, Australia, Belgium, Brazil, Bulgaria, Canada, Chile, Colombia, Croatia, Czech Republic, Denmark, Egypt, Finland, France, Germany, Great Britain, Greece, Guatemala, Hong Kong, Hungary, India, Israel, Italy, Japan, Korea, Kuwait, Latvia, Lithuania, Malaysia, Mexico, New Zealand, Peru, Philippines, Poland, Portugal, Puerto Rico, Romania, Russia, Serbia, Slovakia, South Africa, Spain, Sweden, Taiwan, Thailand, Ukraine, United Arab Emirates and USA
hArgentina, Australia, Brazil, Canada, China, Czech Republic, France, Germany, Hungary, India, Ireland, Italy, Korea, Malaysia, Mexico, The Netherlands, New Zealand, Poland, Romania, Russia, Spain, Sweden, Thailand, United Kingdom, United States
iArgentina, Australia, Belgium, Bulgaria, Brazil, Canada, Chile, China, Colombia, Czech Republic, Estonia, Finland, France, Germany, Great Britain, Hong Kong, Hungary, India, Israel, Italy, Lithuania, Latvia, Malaysia, Netherlands, Norway, New Zealand, Poland, Romania, Russia, Singapore, Slovakia, South Africa, South Korea, Spain, Sweden, Taiwan, Turkey, Ukraine, United States
* The SD value were estimated from IQR according to Cochrane handbook
†Combined data by sample size according to Cochrane handbook
‡Calculated by baseline HbA1c level and HbA1c level in intervention group