Bichu et al and the downstream production of the extracellular matrix protein ﬁbronectin and have been shown to improve insulin sensitivity, reduce triglyceride levels and decrease the risk for atherosclerosis. This has been acknowledged by the trial authors as an explanation for telmisartan’s mechanism of action in vitro and further studies need to be done to demonstrate the action in vivo. Another issue regarding the differences in proteinuria between the groups may relate to a lower blood pressure favoring one group. The trial showed that blood pressure was decreased equally in both groups although not as much as the Captopril Study Group (CSG) (∼3 mmHg in AMADEO versus ∼4 mmHg in CSG). In addition, the telmisartan group separated itself from the losartan group at day 56 by 4.2 mmHg, although this difference was narrower at all other time-points. In the context that the study may be underpowered to detect differences in BP between groups, the authors concluded that the blood pressure differences were not statistically signiﬁcant and larger well-designed trials were needed to detect the effects of such small blood pressure differences on proteinuria. An important observation is that both the treatment arms did not have signiﬁcant side effects but there was a 20% dropout rate for the trial which was consistent in both the arms. Clariﬁcation regarding the reasons for the dropouts was not outlined in the published trial and could be important in the ﬁnal analysis. Another factor that could have affected proteinuria is a disproportionate increase in dietary sodium intake in one group, since this is known to blunt the antiproteinuric effects of the ARB. However, the study detected no differences between groups in sodium excretion. Analysis of the secondary endpoints of AMADEO trial brings forth an interesting trend. Serum aldosterone is an important part of RAAS and evidence points to some of the downstream effects of Ang II are mediated via release of aldosterone. Although not statistically signiﬁcant, the study detected a trend towards greater reductions in aldosterone in the telmisartan group when compared to the losartan group (p = 0.07). The signiﬁcance of this interesting trend is not clear at this point. However, future studies aimed at dissecting the role of telmisartan in ameliorating aldosterone- mediated DKD may answer this question. Baseline s k e e W 13 26 39 52 1,350 1,500 1,650 1,450 1,600 1,650 1,500 1,700 2,000 2,000 Telmisartan Losartan 1,000 1,280 1,560 1,840 2,120 g Mean UPC (mg/g Creatinine) 2,400 Figure 3 Primary endpoint fromAMADEO trial.Patients in the two treatment groups (telmisartan vs losartan) started with the same mean UPC of 2000 mg/g creatinine.Note that the telmisartan arm had signiﬁcantly lower mean UPC at every time-point over the course of the next year when compared to losartan treated patients. Drawn from data of.2 138 Vascular Health and Risk Management 2009:5