Sulfonylureas vs thiazolidinediones for the prevention of diabetic nephropathy
SummaryDailyUpdates 30th March: According to WHO, there are some 130 million diagnosed diabetics in the world and the long term consequences of diabetes such as diabetic nephropathy are becoming increasingly frequent and unmet components of diabetes care. Intensive glycemic control prevents or retards microalbuminuria, an early sign of nephropathy in patients with type 2 diabetes and in a recent study Japanese researchers compare two different classes of oral antidiabetic drugs with respect to their e
Oral antidiabetic drugs have traditionally focussed on metformin and sulphonylurea. Until 1995, the sulfonylurea class of drugs which act by increasing insulin secretion was the only choice in the United States other than insulin for treating type 2 diabetes. The explosion of drugs available for controlling blood glucose began when Glucophage (metformin) became available in 1995, quickly followed by the approval of the insulinotropic agent Repaglinide in 1997 and the thiazolidinedione insulin sensitizers such as Avandia and Actos, which were both launched in 1999.
The prevalence of nephropathy (encompassing microalbuminuria, proteinuria and end-stage renal disease) is 48% in seven countries representing 18.6m type 2 patients. The main focus of therapy in diabetic nephropathy is on tight control of blood pressure and either ACE or ARB therapy is recommended as a first line renoprotective anti-hypertensive therapy. Existing anti-hypertensive therapies can however only delay the progression of diabetic nephropathy. Research elucidating the etiology and pathways of diabetic microvascular disease has revealed new targets for drug design. Within the next 10 years the most promising compounds will come from the ARI, PKC-beta and AGE inhibitor classes.
Intensive glycemic control prevents or retards microalbuminuria, an early sign of nephropathy, in patients with type 2 diabetes, and as well as developing drugs that specifically target diabetic nephropathy it is important to determine whether any of the existing antiglycemics offer a particular advantage with respect to the prevention of microalbuminuria. This issue was addressed in a recent study by Japanese researchers.
In their March Metabolism journal article, Yanagawa et al compare the effect of the sulfonylurea gliclazide (Diamicron) and pioglitazone (Actos) on microalbuminuria in patients with type 2 diabetes. Each patient received the designated drug for 12 weeks. The 2 groups of patients were well matched for age, duration of diabetes, retinal status, blood pressure, body mass index and the use of antihypertensive drugs.
After treatment, no significant differences were seen in drug efficacy between the 2 groups. Gliclazide and pioglitazone significantly reduced fasting plasma glucose, glycated hemoglobin and total cholesterol levels. Decrements in these metabolic parameters were comparable between the groups. Gliclazide and pioglitazone significantly reduced urinary albumin to creatinine ratio with a comparable decrement in both groups.
These results suggest that 12 weeks of treatment with gliclazide or pioglitazone are equally effective in reducing microalbuminuria with similar improvements in blood glucose and cholesterol levels, independent of their mechanisms of actions. On the basis of these data, there does not therefore appear to be a particular advantage in treatment with gliclazide or pioglitazone with respect to the long-term prevention of diabetic nephropathy. Further studies comparing the effects of other examples of sulfonylureas and thiazolidinediones, as well as longer term treatment and investigating combined treatment on microalbuminuria may lead to improvements in our approach to the unmet problem of diabetic nephropathy.
(source DailyUpdates 30th March; for a full abstract of the original papers see Metabolism. 2004 Mar;53(3):353-7; for further information on diabetic nephropathy see Diabetic Nephropathy: Prevalence, Progression, Prevention and Potential)