Use of a dpp-4 inhibitor in sirs and/or sepsis

Abstract

The present invention relates to methods for treating and/or preventing SIRS and/or sepsis comprising the administration of an effective amount of a certain DPP-4 inhibitor, as well as to the use of a certain DPP-4 inhibitor for treating and/or preventing a metabolic disease in a patient with or at risk of SIRS and/or sepsis.

What is claimed is: 
     
         1 . A method for treating, preventing and/or reducing the risk of systemic inflammatory response syndrome (SIRS) and/or sepsis (SIRS/sepsis) in a patient, the method comprising administering to the patient a DPP-4 inhibitor which is of
 formula (I)   
       
         
           
           
               
               
           
         
         or formula (II) 
       
       
         
           
           
               
               
           
         
         or formula (III) 
       
       
         
           
           
               
               
           
         
         or formula (IV) 
       
       
         
           
           
               
               
           
         
         wherein R1 denotes ([1,5]naphthyridin-2-yl)methyl, (quinazolin-2-yl)methyl, (quinoxalin-6-yl)methyl, (4-methyl-quinazolin-2-yl)methyl, 2-cyano-benzyl, (3-cyano-quinolin-2-yl)methyl, (3-cyano-pyridin-2-yl)methyl, (4-methyl-pyrimidin-2-yl)methyl, or (4,6-dimethyl-pyrimidin-2-yl)methyl and R2 denotes 3-(R)-amino-piperidin-1-yl, (2-amino-2-methyl-propyl)-methylamino or (2-(S)-amino-propyl)-methylamino, 
         or a pharmaceutically acceptable salt thereof; 
         optionally in combination with one or more other active agents. 
       
     
     
         2 . The method according to  claim 1 , wherein the DPP-4 inhibitor is linagliptin, optionally in combination with one or more other active agents, and the method is for increasing survival rate and/or reducing mortality, morbidity or hospitalisation of a patient with or at risk of SIRS and/or sepsis (SIRS/sepsis). 
     
     
         3 . The method according to  claim 1  wherein the DPP-4 inhibitor is, optionally in combination with one or more other active agents, and the method is for treating, preventing or reducing the likelihood or risk of complications associated with SIRS and/or sepsis, such as e.g. severe SIRS/sepsis, SIRS/septic shock and/or multi-organ failure. 
     
     
         4 . The method according to  claim 1 , wherein the DPP-4 inhibitor is linagliptin, optionally in combination with one or more other active agents, and the method is for reducing the risk or likelihood of multi-organ failure in a patient with or at risk of SIRS and/or sepsis (SIRS/sepsis). 
     
     
         5 . The method according to  claim 1 , wherein the DPP-4 inhibitor is linagliptin, optionally in combination with one or more other active agents, and the method is for reducing the risk or likelihood of septic shock in a patient with or at risk of SIRS and/or sepsis (SIRS/sepsis). 
     
     
         6 . The method according to  claim 1 , wherein the DPP-4 inhibitor is linagliptin, optionally in combination with one or more other active agents, and the method is for reducing the risk or likelihood of severe sepsis in a patient with or at risk of SIRS and/or sepsis (SIRS/sepsis). 
     
     
         7 . The method according to  claim 1 , wherein the DPP-4 inhibitor is linagliptin, optionally in combination with one or more other active agents, and the method is for treating, preventing or reducing the likelihood or risk of cardiovascular, respiratory, neurologic, hematologic, renal and/or hepatic dysfunction as a complication associated with SIRS/sepsis. 
     
     
         8 . The method according to  claim 1 , wherein the patient has type 1, type 2 diabetes, or LADA. 
     
     
         9 . The method according to  claim 1 , wherein the patient has type 2 diabetes mellitus. 
     
     
         10 . The method according to  claim 1 , wherein the patient is non-diabetic. 
     
     
         11 . The method according to  claim 1 , wherein the patient is impaired in renal function, with renal failure or with nephropathy. 
     
     
         12 . A method for treating and/or metabolic disease, and/or conditions related thereto, in a patient, wherein said patient has or is at risk of systemic inflammatory response syndrome (SIRS) and/or sepsis (SIRS/sepsis), the method comprising administering to said patient linagliptin, optionally in combination with one or more other active agents. 
     
     
         13 . The method according to  claim 12 , wherein the metabolic disease is at least one selected from type 1 diabetes, type 2 diabetes, impaired glucose tolerance (IGT), impaired fasting blood glucose (IFG), hyperglycemia, postprandial hyperglycemia, postabsorptive hyperglycemia, latent autoimmune diabetes in adults (LADA), overweight, obesity, dyslipidemia, hyperlipidemia, hypercholesterolemia, hypertriglyceridemia, hyperNEFA-emia, postprandial lipemia, hypertension, atherosclerosis, endothelial dysfunction, osteoporosis, chronic systemic inflammation, non alcoholic fatty liver disease (NAFLD), retinopathy, neuropathy, nephropathy, polycystic ovarian syndrome, and metabolic syndrome. 
     
     
         14 . A method of using linagliptin, optionally in combination with one or more other active agents, for least one of the following methods:
 preventing, slowing the progression of, delaying the onset of or treating a metabolic disorder or disease, such as e.g. type 1 diabetes mellitus, type 2 diabetes mellitus, impaired glucose tolerance (IGT), impaired fasting blood glucose (IFG), hyperglycemia, postprandial hyperglycemia, postabsorptive hyperglycemia, latent autoimmune diabetes in adults (LADA), overweight, obesity, dyslipidemia, hyperlipidemia, hypercholesterolemia, hypertriglyceridemia, hyperNEFA-emia, postprandial lipemia, hypertension, atherosclerosis, endothelial dysfunction, osteoporosis, chronic systemic inflammation, non alcoholic fatty liver disease (NAFLD), retinopathy, neuropathy, nephropathy, polycystic ovarian syndrome, and/or metabolic syndrome;   improving and/or maintaining glycemic control and/or for reducing of fasting plasma glucose, of postprandial plasma glucose, of postabsorptive plasma glucose and/or of glycosylated hemoglobin HbA1c, or preventing, reducing the risk of, slowing the progression of, delaying the onset of or treating worsening or deterioration of glycemic control, need for insulin therapy or elevated HbA1c despite treatment;   preventing, slowing, delaying the onset of or reversing progression from pre-diabetes, impaired glucose tolerance (IGT), impaired fasting blood glucose (IFG), insulin resistance and/or from metabolic syndrome to type 2 diabetes mellitus;   preventing, reducing the risk of, slowing the progression of, delaying the onset of or treating of complications of diabetes mellitus such as micro- and macrovascular diseases, such as nephropathy, micro- or macroalbuminuria, proteinuria, retinopathy, cataracts, neuropathy, learning or memory impairment, neurodegenerative or cognitive disorders, cardio- or cerebrovascular diseases, tissue ischaemia, diabetic foot or ulcus, atherosclerosis, hypertension, endothelial dysfunction, myocardial infarction, acute coronary syndrome, unstable angina pectoris, stable angina pectoris, peripheral arterial occlusive disease, cardiomyopathy, heart failure, heart rhythm disorders, vascular restenosis, and/or stroke;   reducing body weight and/or body fat and/or liver fat and/or intra-myocellular fat or preventing an increase in body weight and/or body fat and/or liver fat and/or intra-myocellular fat or facilitating a reduction in body weight and/or body fat and/or liver fat and/or intra-myocellular fat;   preventing, slowing, delaying the onset of or treating the degeneration of pancreatic beta cells and/or the decline of the functionality of pancreatic beta cells and/or for improving, preserving and/or restoring the functionality of pancreatic beta cells and/or stimulating and/or restoring or protecting the functionality of pancreatic insulin secretion;   preventing, slowing, delaying the onset of or treating non alcoholic fatty liver disease (NAFLD) including hepatic steatosis, non-alcoholic steatohepatitis (NASH) and/or liver fibrosis (such as e.g. preventing, slowing the progression, delaying the onset of, attenuating, treating or reversing hepatic steatosis, (hepatic) inflammation and/or an abnormal accumulation of liver fat);   preventing, slowing the progression of, delaying the onset of or treating type 2 diabetes with failure to conventional antidiabetic mono- or combination therapy;   achieving a reduction in the dose of conventional antidiabetic medication required for adequate therapeutic effect;   reducing the risk for adverse effects associated with conventional antidiabetic medication (e.g. hypoglycemia or weight gain); and/or   maintaining and/or improving the insulin sensitivity and/or for treating or preventing hyperinsulinemia and/or insulin resistance;   
       in a patient (particularly human patient, such as e.g. human patient having diabetes) with or at risk of systemic inflammatory response syndrome (SIRS) and/or sepsis (SIRS/sepsis). 
     
     
         15 . The method according to  claim 14 , wherein SIRS/sepsis is one or more selected from septic or non-septic SIRS, severe SIRS/sepsis, SIRS/septic shock and multi-organ failure associated with SIRS/sepsis.