Pioglitazone diabetes treatment

Javanovic L, Hassman DR, Gooch B, Jain R, Greco S, Khutoryansky N, Hale PM. Treatment of type 2 diabetes with a combination regimen of repaglinide plus pioglitazone. Diabetes Res Clin Pract 2004 63 127-34. 

A.I. Vinik, P.M.M. Barlow, J. Ullal, C.M. Casellini, H.K. Parson, Pioglitazone treatment improves nit-rosative stress in type 2 diabetes. Diabetes Care 29, 869-876 (2006). 

Chilcott J, Tappenden P, Jones ML, Wight JP. A systematic review of the clinical effectiveness of pioglitazone in the treatment of type 2 diabetes mellitus. Clin Ther 2001 23(ll) 1792-823. 

Aronoff S, Rosenblatt S, Braithwaite S, Egan JW, Mathisen AL, Schneider RLThe Pioglitazone 001 Study Group. Pioglitazone hydrochloride monotherapy improves glycemic control in the treatment of patients with type 2 diabetes a 6-month randomized placebo-controlled dose-response study. Diabetes Care 2000 23(11) 1605-11. 

Hofmann, C., Lorenz, K., and Colca, J. R. (1991). Glucose Transport Deficiency in Diabetic Animals Is Corrected by Treatment with the Oral Antihyperglycemic Agent Pioglitazone. Endocrinology 129, 1915-1925. 

Schneider, R., Lessem, J., and Lekich, R. (1999). Pioglitazone is Effective in the Treatment of Patients with Type 2 Diabetes (Abstract 469). Diabetes48, (Suppl, 1), Al 09. 

Hofmann C, Lorenz K, Colca JR (1991) Glucose transport deficiency in diabetic animals is corrected by treatment with the oral antihyperglycemic agent pioglitazone. Endocrinol 129 1915-1925... 

Diabetic patients often have significant cardiovascular risk factors, which may be exacerbated with TZD treatment. Congestive heart failure in diabetics treated concomitantly with insulin and TZDs has been reported. In placebo controlled trials the incidence of CHF was significantly higher in patients using pioglitazone and insulin (approximately 1%) versus patients on insulin alone [40]. 

All of the thiazolidinediones used clinically have been shown to delay the onset of proteinuria or reduce established proteinuria [16,45 7]. In a small randomized study, pioglitazone significantly reduced urinary albumin excretion from 142.8 to 48.4 mcg/minute after 3 months of treatment in patients with type 2 diabetes and miCToalbuminuria [48]. Rosiglitazone also reduced albumin/creatinine ratio in patients with type 2 diabetes in a dose-dependent fashion [22]. Larger, longer-term studies are necessary to confirm the effects of thiazolidinediones on the delay and improvement of diabetic nephropathy. 

Einhorn D, Rendell M, Rosenzweig 1, et al. Pioglitazone hydrochloride in combination with metformin in the treatment of type 2 diabetes mellitus a randomized, placebo-controlled study. Clin Then 2000 22(12) 1395-1409. 

King AB, Armstrong D. Characteristics of the patients who gain weight while on pioglitazone treatment [abstract 481-P]. Diabetes. 2001 50(suppl 1) A120. 

PPAR agonists have shown great promise as new therapeutics for the treatment of diabetes, dyshpidemia, and related metabolic disorders. Safety has been an issue and a concern, especially due to lack of proper understanding of the mechanism of toxicity and side effects. The compounds are being discontinued from clinical development due to nonspecific tumors seen in a two-year carcinogenicity study in rodents. Pioglitazone, which has been on Ihe market since 2000, had also shown tumors in rodents. However, as the understanding of concern becomes clear, insulin sensitizers would become important therapeutic tools for the treatment of diabetes. 

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