Table 3: Pharmacologic interventions for the prevention of diabetes [22]

Studies/Pharmacologic

Intervention(s)

 

DPP [11] (n = 3234)

STOP-NIDDM5, [17,18]

(n = 1429) Acarbose

DREAM [14] (n = 5269) Rosiglitazone, Ramipril

NAVIGATOR [15]

(n = 9306) Nateglinide, Valsartan

ORIGIN [16] (n = 12537) Insulin Glargine

Eligible participants

 

IGT (a plasma glucose concentration of 95-125 mg/dl (5.3-6.9 mmol/l) in the fasting state and 140-200 mg/dl (7.8-11.1 mmol/l) 2 h after a 75 g oral glucose load)

IGT (2-h plasma glucose concentration between 140 and 200 mg/dl (7.8-11.1 mmol/l) after  a 75 g glucose load and a fasting plasma glucose concentration between 101 and 140 mg/dl; 5.65-7.8mmol/l)

 

IGT (fasting plasma glucose concentration < 126 mg/dl (7.0 mmol/l) and 2-h Plasma glucose concentration between 140 mg/dl (7.8 mmol/l) and 200 mg/dl; 11.1 mmol/l) and/or IFG (fasting plasma glucose concentration between 110 (6.1 mmol/l) and 126 mg/dl (7.0 mmol/l) and 2-h plasma glucose concentration < 200 mg/dl (11.1 mmol/l) during OGTT) without known CVD or renal insufficiency

IGT (defined as 2-h plasma glucose concentration between 140 and 200 mg/dl (7.8 and 11.1 mmol/l)  after a 75 g glucose load and a

fasting plasma glucose

concentration between 95 and 126 mg/dl; 5.3 and 7.0 mmol/l) and established cardiovascular disease

or cardiovascular risk factors

Subjects with a prior CV event; angina+documented ischaemia; albuminuria; left ventricular hypertrophy; angiographic evidence of > 50% stenosis of a coronary, carotid or lower extremity artery; or an ankle/brachial index < 0.9 were recruited if they also had a history of type 2 diabetes that was stable on 0 or 1 oral glucose lowering agents; or IFG, IGT or newly detected diabetes based on either a FPG ≥ 6.1 mmol/l [110 mg/dl] or a 2h plasma glucose ≥ 7.8 mmol/l [140 mg/dl] after a 75 g oral glucose load

Mean age(yrs)

51

54

55

64

63.5

BMI (kg/m2)

 

34

31

31

Nateglinide:31

Valsartan: 30

Insulin glargine: 29.8

Placebo: 29.9

Primary outcome

 

Incident diabetes diagnosed with annual OGTT or semiannual fasting plasma glucose test

Incident diabetes diagnosed on

An annual OGTT

 

Incident diabetes (OGTT performed at year 2 and study end, FPG collected

annually) or all-cause mortality

Incident diabetes (FPG semi-annually for 3 year, then annually; annual

OGTTs), extended and core CV outcomes

CV end-points

Median follow-up for incident of diabetes (years)

2.8

3.3

3.0

5.0

6.2

Risk reduction of diabetes progression (%)

31%

25%

Rosiglitazone:62%

Ramipril: no effect

Nateglinide: no effect

Valsartan: 14%

30%

Risk reduction of CVD

Not measured

49% reduction in CV events

No

No

No

 

 

Definition of diabetes

 

 

FPG ≥ 126 mg/dl (7.0 mmol/l) or 2 hr ≥ 200 mg/dl (11.1 mmol/l)

2h  ≥ 200 mg/dl (11.1 mmol/l)

FPG ≥ 126 mg/dl (7.0 mmol/l) or 2 h ≥ 200 mg/dl (11.1 mmol/l), confirmed by a second test or physician diagnosed diabetes supported by prescription of an antidiabetic agent and confirmatory testing

 

FPG ≥ 126 mg/dl (7.0 mmol/l) or 2h ≥ 200 mg/dl (11.1 mmol/l), confirmed by a second test

Either 1. Two consecutive FPG levels within a 4-month period > 126 mg/dl (7.0 mmol/l); 2. a diagnosis of diabetes made by a physician (a), plus use of a pharmacologic antidiabetic agent (b), plus evidence of a FPG of  ≥ 126mg/dl (7.0 mmol/l), or any blood glucose ≥ 200 mg/dl (11.1 mmol/l) OR 3. evidence (a) of at least one capillary glucose ≥ 200mg/dl (11.1 mmol/l) confirmed by FPG ≥ 126 mg/dl (7.0 mmol/l) or (b) of a random glucose ≥ 200 mg/dl (11.1 mmol/l) FPG ≥ 126 mg/dl (7.0 mmol/l) OR 2h plasma glucose > 200 mg/dl; 11.1 mmol/l) during either the 1st or 2nd  OGTT after the end of usual follow-up

Most common or important adverse event

 

 

Gastrointestinal symptoms

Gastrointestinal symptoms

Rosiglitazone: edema, weight gain and non-fatal congestive heart failure Ramipril: cough

Nateglinide: hypoglycaemia

Valsartan: hypotension-related adverse events

Hypoglycaemia, weight gain

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

Abbreviations:

BMI: Body mass index, DREAM: Diabetes REduction Assessment with ramipril and rosiglitazone Medication, DPP: Diabetes Prevention Program, FPG: Fasting plasma glucose, IGT: Impaired glucose tolerance, IFG: Impaired fasting glucose, NAVIGATOR: Nateglinide and Valsartan in Impaired Glucose Tolerance Outcomes Research trial, ORIGIN: Outcome Reduction with Initial Glargine Intervention, OGTT: Oral glucose tolerance test, OR: Odds ratio, STOP-NIDDM: Study to Prevent Non-insulin-dependent Diabetes Mellitus.