A	B
1
2
3		DCCT - Diabetes Control and Complications Trial
4		British Journal of Diabetes and Vascular Disease. 2004;4(1)
5		n=1,441 T1D pts enrolled, n=726 within first five yrs of developing diabetes, n=715 within first fifteen yrs
6		Follow-up was min 4 yrs w avg of 6.5 yrs
7		Of 1,430 alive at end of study, 1,422 evaluable outcomes
8		Results show that intensive tx delays onset & slows progression of diabetic retinopathy, diabetic nephropathy & diabetic neuropathy
9		For intensive tx group, 3-fold risk of severe hypoglycaemia, incl 3x risk of coma or seizures, and weight gain.
10		Macrovascular events (cardiac or peripheral vascular) were not significantly reduced. When episodes of both were combined, there was a 41% risk reduction (p=0.06).
11
12		UKPDS - UK Prospective Diabetes Study
13		n=5,102 newly diagnosed T2D pts, follow-up
14		n=1,138 conventional tx (CT) initially w diet alone, then non-intensive tx
15		n=2,729 intensive tx w sulphonylurea or insulin, on sulphonylurea add metformin/move to insulin tx, on insulin transfer to complex regimens
16		diabetes-related death (MI/sudden death, fatal stroke, peripheral vasc disease, renal disease, hyper/hypoglycemia), p=0.34
17		MI (cumulative) b/n intensive vs conventional p=0.052
18		Intensive tx was better than conventional therapy on all endpoints except stroke, where RR = 1.1 and p=0.52
19		no evidence of deleterious effect on MI, sudden death or diabetes-related death
20		no evidence for more atheroma-related disease
21		metformin in overweight pts compared w conventional tx statistically significantly reduced all-cause mortality by 36% (p=0.011) and MI by 39% (p=0.01)
22
23		ADOPT - A Diabetes Outcome Progression Trial
24		n=4,360 drug-naïve pts w T2D diagnosed w/in past 3 yrs randomized to rosiglitazone, glyburide or metformin, treated for 4-6 yrs
25		edema and weight gain were common adverse events, along with CHF
26
27
28		PROactive - Prospective Pioglitazone Clinical Trial in Macrovascular Events
29		n=5.238 T2D w history of macrovascular disease
30		Primary endpoint was combination of 7 different macrovascular events of varying clinical important (what were these?)
31		The primary endpoint was reduced by 10% but was not statistically significant (p=0.095). The principal secondary endpoint of life-threatening events showed a reduced risk of MI, strokes and death by 16% (p=0.027)
32		Lipid profile improved: HDL increased by 9% more than placebo (p<0.001) and reduced TG by 13% more than placebo (p<0.001)
33		Side effects incl weight gain, edema, non-serious hypoglycemia and heart failure.