Treatment for diabetes in patients inappropriate for metformin therapy

Abstract

The present invention relates to the finding that certain DPP-4 inhibitors are particularly suitable for treating and/or preventing metabolic diseases, particularly diabetes, in patients for whom metformin therapy is inappropriate due to intolerability or contraindication against metformin.

What is claimed is: 
     
         1 . A method of treating and/or preventing a metabolic disorder in a patient for whom metformin therapy is inappropriate due to contraindication against metformin comprising orally administering 3-{(2S,4S)-4-[4-(3-methyl-1-phenyl-1H-pyrazol-5-yl)piperazin-1-yl]pyrrolidin-2-ylcarbonyl}thiazolidine, or a pharmaceutically acceptable salt thereof, to the patient, wherein
 the metabolic disorder is type 2 diabetes mellitus and the contraindication is renal impairment, and wherein   3-{(2S,4S)-4-[4-(3-Methyl-1-phenyl-1H-pyrazol-5-yl)piperazin-1-yl]pyrrolidin-2-ylcarbonyl}thiazolidine, or a pharmaceutically acceptable salt thereof, is administered to the patient in the same dose as for a patient with normal renal function.   
     
     
         2 . The method according to  claim 1  wherein the patient is ineligible for metformin therapy due to contraindication against metformin. 
     
     
         3 . The method according to  claim 1  wherein the patient is in need of reduced dose metformin therapy due to contraindication against metformin. 
     
     
         4 . The method according to  claim 1 , wherein 3-{(2S,4S)-4-[4-(3-methyl-1-phenyl-1H-pyrazol-5-yl)piperazin-1-yl]pyrrolidin-2-ylcarbonyl}thiazolidine and its major active metabolite(s) have a relatively wide therapeutic window and/or are primarily eliminated via hepatic metabolism or biliary excretion. 
     
     
         5 . The method according to  claim 1 , wherein 3-{(2S,4S)-4-[4-(3-methyl-1-phenyl-1H-pyrazol-5-yl)piperazin-1-yl]pyrrolidin-2-ylcarbonyl}thiazolidine is excreted mainly via the liver. 
     
     
         6 . The method according to  claim 1 , for which excretion via the kidney represents a minor elimination pathway of 3-{(2S,4S)-4-[4-(3-methyl-1-phenyl-1H-pyrazol-5-yl)piperazin-1-yl]pyrrolidin-2-ylcarbonyl}thiazolidine. 
     
     
         7 . The method according to  claim 1 , wherein 3-{(2S,4S)-4-[4-(3-methyl-1-phenyl-1H-pyrazol-5-yl)piperazin-1-yl]pyrrolidin-2-ylcarbonyl}thiazolidine is excreted mainly unchanged. 
     
     
         8 . The method according to  claim 1 , for which elimination of 3-{(2S,4S)-4-[4-(3-methyl-1-phenyl-1H-pyrazol-5-yl)piperazin-1-yl]pyrrolidin-2-ylcarbonyl}thiazolidine via metabolism represents a minor elimination pathway. 
     
     
         9 . The method according to  claim 1 , wherein 3-{(2S,4S)-4-[4-(3-methyl-1-phenyl-1H-pyrazol-5-yl)piperazin-1-yl]pyrrolidin-2-ylcarbonyl}thiazolidine has placebo-like safety/tolerability and/or is eliminated primarily as the parent drug via the liver. 
     
     
         10 . The method according to  claim 1 , wherein the main metabolite of 3-{(2S,4S)-4-[4-(3-methyl-1-phenyl-1H-pyrazol-5-yl)piperazin-1-yl]pyrrolidin-2-ylcarbonyl}thiazolidine is pharmacologically inactive or has a relatively wide therapeutic window. 
     
     
         11 . The method according to  claim 1  wherein the contraindication is mild, moderate or severe renal impairment or end-stage renal disease. 
     
     
         12 . The method according to  claim 1 , wherein 3-{(2S,4S)-4-[4-(3-methyl-1-phenyl-1H-pyrazol-5-yl)piperazin-1-yl]pyrrolidin-2-ylcarbonyl}thiazolidine, or a pharmaceutically acceptable salt thereof, is administered in combination with one or more further active substances selected from antidiabetics, active substances that lower the blood sugar level, active substances that lower the lipid level in the blood, active substances that raise the HDL level in the blood, active substances that lower the blood pressure, active substances that are indicated in the treatment of atherosclerosis, and active substances that are indicated in the treatment of obesity. 
     
     
         13 . The method according to  claim 1 , wherein 3-{(2S,4S)-4-[4-(3-methyl-1-phenyl-1H-pyrazol-5-yl)piperazin-1-yl]pyrrolidin-2-ylcarbonyl}thiazolidine, or a pharmaceutically acceptable salt thereof, is administered in combination with one or more further active substances selected from sulphonylureas, thiazolidinediones, glinides, alpha-glucosidase blockers, GLP-1 and GLP-1 analogues, and insulin and insulin analogues. 
     
     
         14 . The method according to  claim 1 , wherein 3-{(2S,4S)-4-[4-(3-methyl-1-phenyl-1H-pyrazol-5-yl)piperazin-1-yl]pyrrolidin-2-ylcarbonyl}thiazolidine, or a pharmaceutically acceptable salt thereof, is administered in combination with one or more further active substances selected from repaglinide, pioglitazone, and insulin and insulin analogues. 
     
     
         15 . The method according to  claim 1 , wherein 3-{(2S,4S)-4-[4-(3-methyl-1-phenyl-1H-pyrazol-5-yl)piperazin-1-yl]pyrrolidin-2-ylcarbonyl}thiazolidine, or a pharmaceutically acceptable salt thereof, is administered in combination with pioglitazone.