Table 3.
Overview of principal diabetes prevention trials with and without evaluation of metformin
| Trial | Design | Subjects | N; duration (years) | Control group | Active treatments | % change in diabetes risk |
|---|---|---|---|---|---|---|
| Principal diabetes prevention trials that evaluated metformin | ||||||
| DPP (US) [19] | RCT | IGT and high–normal glucose | 3234; 3 | Placebo plus standard lifestyle advice | Metformin plus standard lifestyle advice Intensive lifestyle intervention |
−31 −58 |
| DPP Outcome Study (US) [69] | O | Epidemiological follow-up to DPP | 2766; 5.7 | Placebo plus intensive lifestyle advice | Metformin 1700 mg/day + intensive lifestyle advice Intensive lifestyle advice |
−13 +5 |
| IDPP (India) [20, 65] | RCT | IGT | 531; 2.5 | Standard lifestyle advice | Metformin plus standard lifestyle advice Metformin plus intensive lifestyle intervention Intensive lifestyle intervention |
−26 −28 −29 |
| Wenying et al. (China) [68] | NR | IGT | 321; 3 | Standard lifestyle advice | Metformin Acarbose Intensive lifestyle intervention |
−88 −87 −43 |
| Li et al. (China) [66] | RCT | IGT | 70; 1 | Placebo | Metformin | −66a |
| Iqbal Hydrie et al. (Pakistan) [67] | RCT | IGT | 317; 1.5 | Standard lifestyle advice | Metformin Intensive lifestyle intervention |
−76.5 −71 |
| CANOE (Canada) [64] | RCT | IGT | 207; 3.9 | Placebo | Metformin 500 mg plus rosiglitazone 2 mg twice daily | −66 |
| Principal diabetes prevention trials that did not evaluate metformin | ||||||
| Diabetes Prevention Study (Finland) [70] | RCT | IGT | 522; 3.2 | Standard lifestyle advice | Intensive, multifactorial lifestyle intervention | −58 |
| Da Qing study (China) [71] | RBS | IGT | 577; 6 | Standard lifestyle advice | Diet, exercise, or both together | −31 to −46 |
| STOP-NIDDM (Internationalb) [72, 73] | RCT | IGT | 1429; 3.3 | Placebo | Acarbose | −25 |
| XENDOS (Sween) [74] | RCT | IGT and obesity | 694; 4c | Placebo | Orlistat | −45 |
| DREAM (21 countriesd) [75, 76] | RCT | IGT ± IFG | 5269; 3 | Placebo Placebo |
Rosiglitazone Ramipril |
–62e
–9f (NS) |
| IDPP–2 (India) [77] | NRf | IGT | 407; 3 | Placebo + lifestyle intervention | Pioglitazone + lifestyle intervention | +8 (NS) |
| SOS study (Sweden) [78] | RCT | Obese, non-diabetic | 3429; 10 | No surgeryg | Bariatric surgery | –83 |
All studies employed a randomised design, with the exception of the Wenying study
CANOE low-dose combination therapy with rosiglitazone and metformin to prevent type 2 diabetes mellitus trial, DREAM Diabetes Reduction Assessment with Ramipril and Rosiglitazone Medication, IDDP-2 Indian Diabetes Prevention Programme–2, SOS Swedish Obese Subjects, STOP-NIDDM Study to Prevent Non-Insulin-Dependent Diabetes Mellitus, XENDOS Xenical in the Prevention of Diabetes in Obese Subjects, NR non-randomised, O observational follow-up study, RBS randomised by site, RCT randomised controlled trial, NS not significantly different relative to the control group shown, DPP Diabetes Prevention Programme, IGT impaired glucose tolerance, IFG impaired fasting glucose
aFrom data presented (diabetes developed in 16 % of the placebo group and 3 % of the metformin group)
bCanada, Germany, Austria, Norway, Denmark, Sweden, Finland, Israel, Spain
cSubjects with IGT (the overall trial population comprised 3305 subjects)
dArgentina, Australia, Brazil, Canada. Chile, Finland, Germany, Hungary, India, Latvia, Mexico, The Netherlands, Norway, Poland, Slovakia, Spain, Sweden, Sweden, Turkey, UK, US
eRreduction in the risk of the primary outcome (diabetes or death) for rosiglitazone vs. placebo
fSubjects were allocated to groups sequentially
gSubjects from the study cohort were matched to the surgical intervention group using 18 variables