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Rosiglitazone reduces blood pressure and urinary albumin excretion in type 2 diabetes: G Bakris et al

Journal of Human Hypertension volume 17, pages 5–6 (2003)Cite this article

Diabetic nephropathy has become the leading cause of end-stage renal disease (ESRD), currently accounting for approximately 50% % of all new cases of chronic renal failure in the USA.1 Several risk factors accelerate the progression to ESRD in patients with type II diabetes mellitus. These factors include genetic susceptibility, elevated blood pressure, poor glycaemic control, microalbuminuria, increased glomerular filtration rate, obesity, and smoking. Microalbuminuria is the earliest clinical feature of diabetic nephropathy; it is also an indicator of target organ damage, and correction of microalbuminuria in itself will reduce vascular injury and vascular leakage. Lowering blood pressure and improved glycaemic control reduce microalbuminuria. Antihypertensive treatment has a renoprotective effect in hypertensive patients with type II diabetes and microalbuminuria.2 Until recently, however, it was not clear whether all antihypertensive agents are equally effective in reducing microalbuminuria. Recent studies showed that, in patients with type II diabetes, blocking the renin angiotensin system with angiotensin receptor blockers has an additional beneficial antiproteinuric effect beyond the hypotensive effect.3,4,5 Improved glycaemic control reduces microvascular complications and may also reduce or arrest the progression of microalbuminuria.6 It is a great challenge, however, to achieve good glycaemic control in patients with type II diabetes mellitus. The thiazolidinediones class of compounds recently became available for clinical use in diabetic patients. This class of agents activates the PPARγ, and thereby decreases insulin resistance at the level of the muscle and increases glucose intake. Insulin resistance, along with the compensatory hyperinsulinaemia, not only contributes to hyperglycaemia but may also play a pathophysiologic role in other metabolic abnormalities such as hypertriglyceridaemia, low levels of high-density lipoprotein cholesterol, hypertension, abnormal fibrinolysis and coronary heart disease. Because thiazolidinediones directly improve insulin resistance and reduce insulin levels, it has been proposed that they may correct other abnormalities of the insulin resistance syndrome as well as improve hyperglycaemia. In animal models, therapy with agents of the thiazolidinediones class decreased arterial pressure and protected against nephropathy;7,8,9,10 it is unclear, however, whether they will also work in humans. The paper by Bakris et al11 in this issue shows that rosiglitazone – a thiazolidinedione agent – reduces urinary albumin excretion after 52 weeks, whereas glyburide does not reduce urinary albumin excretion despite similar control of blood glucose levels. Because both agents controlled blood glucose equally, it seems that glycaemic control is not sufficient to repair vascular damage and reduce albuminuria. Troglitazone – a thiazolidinedione agent – has been found to decrease blood pressure substantially.12,13 In the study by Bakris et al,11 rosiglitazone lowered blood pressure significantly more than glyburide, as observed by ambulatory blood pressure monitoring. In patients with type II diabetes mellitus even a slight reduction in blood pressure protects the cardiovascular system.14,15 It is unclear, therefore, whether the beneficial effect of rosiglitazone in reducing microalbuminuria is mediated through blood pressure reduction or via direct vasculo-protective mechanisms. Regardless of the mechanism, it is important to know that rosiglitazone not only controls blood glucose levels in patients with type II diabetes mellitus but also reduces blood pressure and microalbuminuria. Since optimal treatment for type II diabetes mellitus should aim to control not only glucose levels but also other cardiovascular risk factors, it seems that rosiglitazone may be an ideal treatment for type II diabetes mellitus. Some increases in adverse events, such as weight gain, oedema, increased low-density lipoprotein cholesterol concentration, lowering of haemoglobin, may prevent this drug from becoming the drug of choice in type II diabetes mellitus. Further long-term clinical trials of rosiglitazone with cardiovascular and other pertinent endpoints, such as ADOPT, BARI-2D, RECORD and DREAM are underway and will reveal whether the advantages of this drug will translate into clinical benefit to make it a drug of choice in type II diabetes mellitus.

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  1. Internal Medicine D, The Chaim Sheba Medical Center, Tel-Hashomer, 52621, Israel

    E Grossman

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Grossman, E. Rosiglitazone reduces blood pressure and urinary albumin excretion in type 2 diabetes: G Bakris et al. J Hum Hypertens 17, 5–6 (2003). https://doi.org/10.1038/sj.jhh.1001474

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