Therapy for complications of diabetes

Abstract

A method for enhancing glycemic control and / or insulin sensitivity in a human subject having diabetic nephropathy and / or metabolic syndrome comprises administering to the subject a selective endothelin A (ETA) receptor antagonist in a glycemic control and / or insulin sensitivity enhancing effective amount. A method for treating a complex of comorbidities in an elderly diabetic human subject comprises administering to the subject a selective ETA receptor antagonist in combination or as adjunctive therapy with at least one additional agent that is (i) other than a selective ETA receptor antagonist and (ii) effective in treatment of diabetes and / or at least one of said comorbidities other than hypertension. A therapeutic combination useful in such a method comprises a selective ETA receptor antagonist and at least one antidiabetic, anti-obesity or antidyslipidemic agent other than a selective ETA receptor antagonist.

Description

[0001]This application claims the benefit of U.S. provisional application Serial No. 60 / 957,300 filed on Aug. 22, 2007, the disclosure of which is incorporated herein by reference in its entirety. Further, this application contains subject matter related to copending U.S. application Ser. No. 11 / 509,897, the disclosure of which is incorporated herein by reference in its entirety without admission that such disclosure constitutes prior art to the present invention.FIELD OF THE INVENTION[0002]The present invention relates to methods and therapeutic combinations useful for improving clinical outcomes in diabetic patients having complications of diabetes such as diabetic nephropathy and / or metabolic syndrome.BACKGROUND OF THE INVENTION[0003]Hyperglycemia in diabetes mellitus, if not controlled, over time causes certain irreversible morphologic changes including glomerular fibrosis in kidneys of affected subjects, a condition known as diabetic nephropathy that is associated with decline ...

AI Technical Summary

Benefits of technology

[0030]There is now provided a method for enhancing glycemic control and / or insulin sensitivity in a human subject having diabetic nephropathy and / or metabolic syndrome, comprising administering to the subject a selective endothelin A (ETA) receptor antagonist in a glycemic control and / or insulin sensitivity enhancing effective amount.

Problems solved by technology

In type 1 (insulin-dependent) diabetes, glycemic control is usually achievable with chronic insulin therapy; however, in type 2 (non-insulin-dependent) diabetes, insulin alone may be ineffective in preventing hyperglycemia.

Even in patients with type 1 diabetes, insulin sensitivity can be partially or completely lost.

Diabetic nephropathy and metabolic syndrome are serious complications of diabetes that can dramatically reduce quality of life and survival time.

A feature of both these complications is arterial hypertension, which superimposes risk of serious cardiac adverse events on the already high risk of chronic kidney failure arising from these complications.

Recognizing that elevated blood pressure occurs in both diabetic nephropathy and metabolic syndrome, and brings its own attendant risks to quality of life and survival time, an even more challenging patient population comprises subjects having at least one of these complications of diabetes and exhibiting inadequate blood pressure control by standard antihypertensive therapies.

Further, resistant hypertension is diagnosed by many physicians on the basis of a patient's resistance to adequate, but less than full, doses of an appropriate three-drug regimen because of the risk or occurrence of adverse events associated with full doses.

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