Table 3: Pharmacologic interventions for
the prevention of diabetes [22]
Studies/Pharmacologic Intervention(s) |
DPP [11] (n =
3234) |
(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.