Pharmaceutical composition, methods for treating and uses thereof

Abstract

The present invention relates to certain SGLT-2 inhibitors for treating, preventing, protecting against and/or delaying the progression of chronic kidney disease in patients, for example patients with prediabetes, type 1 or type 2 diabetes mellitus.

1 . A method of treating, preventing, protecting against, reducing the risk of, delaying the occurrence of and/or delaying the progression of chronic kidney disease in a patient, said method comprising administering empagliflozin, optionally in combination with one or more other therapeutic substances, to the patient. 
     
     
         2 . The method according to  claim 1 , wherein the progression of said chronic kidney disease is the progression to end stage renal disease/kidney failure, or renal death in the patient. 
     
     
         3 . The method according to  claim 1 , wherein said patient is at risk for renal disease. 
     
     
         4 . The method according to  claim 1 , wherein the patient is a patient with prediabetes, type 1 or type 2 diabetes mellitus. 
     
     
         5 . The method according to  claim 1 , wherein the patient has or is at risk of a cardiovascular disease. 
     
     
         6 . The method according to  claim 1 , wherein the patient is a patient with prediabetes, type 1 or type 2 diabetes mellitus and with or at risk of a cardiovascular disease. 
     
     
         7 . A method of treating, preventing, protecting against or delaying new onset of albuminuria in a patient, said method comprising administering empagliflozin, optionally in combination with one or more other therapeutic substances, to the patient. 
     
     
         8 . The method according to  claim 7 , wherein said patient is at risk for renal disease. 
     
     
         9 . The method according to  claim 7 , wherein the patient is a patient with prediabetes, type 1 or type 2 diabetes mellitus. 
     
     
         10 . The method according to  claim 7 , wherein the patient has or is at risk of a cardiovascular disease. 
     
     
         11 . The method according to  claim 7 , wherein the patient is a patient with prediabetes, type 1 or type 2 diabetes mellitus and with or at risk of a cardiovascular disease. 
     
     
         12 . A method of treating, preventing, protecting against or delaying the progression from no albuminuria to micro- or macroalbuminuria in a patient at risk for renal disease, said method comprising administering empagliflozin, optionally in combination with one or more other therapeutic substances, to the patient. 
     
     
         13 . The method according to  claim 12 , wherein the patient is a patient with prediabetes, type 1 or type 2 diabetes mellitus. 
     
     
         14 . A method of treating, preventing, protecting against or delaying the progression from microalbuminuria to macroalbuminuria in a patient with chronic kidney disease, said method comprising administering empagliflozin, optionally in combination with one or more other therapeutic substances, to the patient. 
     
     
         15 . The method according to  claim 14 , wherein the patient is a patient with prediabetes, type 1 or type 2 diabetes mellitus. 
     
     
         16 . A method for treating, preventing, protecting against or delaying the progression of chronic kidney disease in a patient, said method administering empagliflozin, optionally in combination with one or more other therapeutic substances, to the patient. 
     
     
         17 . The method according to  claim 16 , comprising preventing, protecting against or delaying loss of eGFR, for example sustained eGFR loss of ≧50%, in said patient. 
     
     
         18 . The method according to  claim 16 , wherein the patient is a patient with prediabetes, type 1 or type 2 diabetes mellitus. 
     
     
         19 . A method of treating, preventing, protecting against or delaying the occurrence of:
 new onset of albuminuria,   doubling of serum creatinine level accompanied by an eGFR (based on modification of diet in renal disease (MDRD) formula)≦45 mL/min/1.73 m 2 ,   need for continuous renal replacement therapy, or   death due to renal disease,   in a patient, said method comprising administering empagliflozin, optionally in combination with one or more other therapeutic substances, to the patient.   
     
     
         20 . The method according to  claim 19 , wherein the patient has chronic kidney disease. 
     
     
         21 . The method according to  claim 19 , wherein the patient is a patient with prediabetes, type 1 or type 2 diabetes mellitus. 
     
     
         22 . The method according to  claim 19 , wherein the patient has or is at risk of a cardiovascular disease. 
     
     
         23 . The method according to  claim 19 , wherein the patient is a patient with prediabetes, type 1 or type 2 diabetes and with or at risk of a cardiovascular disease. 
     
     
         24 . The method according to  claim 19 , wherein the patient has chronic kidney disease and is a patient with prediabetes, type 1 or type 2 diabetes mellitus. 
     
     
         25 . The method according to  claim 1 , wherein the patient is a patient with one or more cardiovascular risk factors selected from A), B), C) and D):
 A) previous or existing vascular disease selected from myocardial infarction, coronary artery disease, percutaneous coronary intervention, coronary artery by-pass grafting, ischemic or hemorrhagic stroke, congestive heart failure, and peripheral occlusive arterial disease,   B) advanced age>/=60-70 years, and   C) one or more cardiovascular risk factors selected from
 advanced type 1 or type 2 diabetes mellitus>10 years duration, 
 hypertension, 
 current daily cigarette smoking, 
 dyslipidemia, 
 obesity, 
 age>/=40, 
 metabolic syndrome, hyperinsulinemia or insulin resistance, and 
 hyperuricemia, erectile dysfunction, polycystic ovary syndrome, sleep apnea, or family history of vascular disease or cardiomyopathy in first-degree relative; 
   D) one or more of the following:
 confirmed history of myocardial infarction, 
 unstable angina with documented multivessel coronary disease or positive stress test, 
 multivessel Percutaneous Coronary Intervention, 
 multivessel Coronary Artery By-pass Grafting (CABG), 
 history of ischemic or hemorrhagic stroke, 
 peripheral occlusive arterial disease. 
   
     
     
         26 . The method according to  claim 1 , wherein the one or more other therapeutic substances are selected from other antidiabetic substances. 
     
     
         27 . The method according to  claim 1 , comprising administering empagliflozin in combination with metformin, with linagliptin or with metformin and linagliptin. 
     
     
         28 . The method according to  claim 1 , wherein the one or more other therapeutic substances is a RAAS inhibitor. 
     
     
         29 . The method according to  claim 1 , wherein the one or more other therapeutic substances is a direct renin inhibitor, an Angiotensin-Converting Enzyme (ACE) inhibitor and/or an angiotensin II receptor blocker (ARB). 
     
     
         30 . The method according to  claim 1 , comprising administering empagliflozin in combination with a RAAS inhibitor. 
     
     
         31 . The method according to  claim 1 , comprising administering empagliflozin in combination with a direct renin inhibitor, an Angiotensin-Converting Enzyme (ACE) inhibitor and/or an angiotensin II receptor blocker (ARB). 
     
     
         32 . The method according to  claim 1 , wherein empagliflozin is administered orally in a total daily amount of 10 mg or 25 mg. 
     
     
         33 . The method according to  claim 1 , wherein empagliflozin is administered as a pharmaceutical composition comprising 10 mg or 25 mg of empagliflozin.