Pharmaceutical composition, methods for treating and uses thereof

Abstract

The present invention relates to certain SGLT-2 inhibitors for treating and/or preventing oxidative stress, for example in patients with type 1 or type 2 diabetes, as well as to the use of such SGLT-2 inhibitors in treatment and/or prevention of cardiovascular diseases in patients, for example type 1 or type 2 diabetes patients. The present invention further relates to certain SGLT-2 inhibitors for treating and/or preventing a metabolic disorder and preventing, reducing the risk of or delaying the occurrence of a cardiovascular event in patients, for example patients with type 1 or type 2 diabetes.

1 ) A method for treating and/or preventing oxidative stress, collagen deposition, vessel wall thickening, vascular stress and/or endothelial dysfunction comprising administering empagliflozin, optionally in combination with one or more other therapeutic substances, to a patient in need thereof. 
     
     
         2 ) The method of  claim 1 , wherein the patient is a non-diabetic patient or a type 2 or type 1 diabetes mellitus patient. 
     
     
         3 ) The method of  claim 1 , wherein the method is for treating and/or preventing endothelial dysfunction in a type 2 or type 1 diabetes mellitus patient. 
     
     
         4 ) A method of treating type 2 or type 1 diabetes mellitus in a patient with or at risk of oxidative stress, vascular stress and/or endothelial dysfunction, or diseases or conditions related or associated therewith,
 said method comprising administering empagliflozin, optionally in combination with one or more other therapeutic substances, to the patient.   
     
     
         5 ) The method according to  claim 4 , wherein said patient has or is at risk of a cardiovascular disease. 
     
     
         6 ) The method according to  claim 4 , wherein the patient has or is at risk of a cardiovascular disease selected from myocardial infarction, stroke, peripheral arterial occlusive disease. 
     
     
         7 ) A method of preventing, reducing the risk of or delaying the occurrence of a cardiovascular event in a patient with type 2 or type 1 diabetes mellitus or with pre-diabetes, 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 has or is at risk of a cardiovascular disease. 
     
     
         9 ) The method according to  claim 7 , wherein the patient has or is at risk of a cardiovascular disease selected from myocardial infarction, stroke, peripheral arterial occlusive disease. 
     
     
         10 ) A method of treating a metabolic disorder and preventing, reducing the risk of or delaying the occurrence of a cardiovascular event in a patient comprising administering empagliflozin, optionally in combination with one or more other therapeutic substances, to the patient. 
     
     
         11 ) The method accoding to  claim 10 , wherein said metabolic disorder is type 2 or type 1 diabetes mellitus or pre-diabetes. 
     
     
         12 ) The method according to  claim 10 , wherein said cardiovascular event is selected from cardiovascular death, non-fatal myocardial infarction, non-fatal stroke, hospitalisation for unstable angina pectoris and heart failure requiring hospitalization 
     
     
         13 ) The method according to  claim 10 , wherein said cardiovascular death is due to fatal myocardial infarction or fatal stroke. 
     
     
         14 ) The method according to  claim 10 , wherein the patient is a patient with type 2 or type 1 diabetes mellitus or with pre-diabetes 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 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. 
   
     
     
         15 ) A method of treatment comprising:
 a) identifying a patient in need of treatment for type 2 or type 1 diabetes mellitus and with or at risk of cardiovascular disease; and   b) administering empagliflozin to said patient.   
     
     
         16 ) The method according to  claim 15 , wherein the patient has or is at risk of a cardiovascular disease selected from myocardial infarction, stroke, peripheral arterial occlusive diasease. 
     
     
         17 ) The method according to  claim 15 , wherein the patient is a patient with type 2 or type 1 diabetes mellitus or with pre-diabetes 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 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. 
   
     
     
         18 ) A method for preventing, slowing, delaying or treating the degeneration of pancreatic beta cells and/or the decline of the functionality of pancreatic beta cells and/or for improving and/or restoring and/or stimulating and/or protecting the functionality of pancreatic beta cells and/or restoring the functionality of pancreatic insulin secretion in a patient having latent autoimmune diabetes in adults (LADA) comprising administering empagliflozin, optionally in combination with one or more other therapeutic substances, to the patient. 
     
     
         19 ) The method according to  claim 18 , wherein the patient having LADA is a patient in whom one or more autoantibodies selected from GAD (GAD-65, anti-GAD), ICA, IA-2A, ZnT8 (anti-ZnT8) and IAA are present. 
     
     
         20 ) A method for preserving pancreatic beta cells and/or their function in a patient having latent autoimmune diabetes in adults (LADA) comprising administering empagliflozin, optionally in combination with one or more other therapeutic substances, to the patient. 
     
     
         21 ) The method according to  claim 20 , wherein the patient having LADA is a patient in whom one or more autoantibodies selected from GAD (GAD-65, anti-GAD), ICA, IA-2A, ZnT8 (anti-ZnT8) and IAA are present. 
     
     
         22 ) A method for treating and/or preventing LADA (latent autoimmune diabetes of adults) in a patient, the method comprising administering empagliflozin, optionally in combination with one or more other therapeutic substances, to the patient. 
     
     
         23 ) The method according to  claim 22 , wherein the patient having LADA is a patient in whom one or more autoantibodies selected from GAD (GAD-65, anti-GAD), ICA, IA-2A, ZnT8 (anti-ZnT8) and IAA are present. 
     
     
         24 ) A method for reducing arterial stiffness in a patient comprising administering empagliflozin to the patient, optionally in combination with one or more other therapeutic substances, to the patient. 
     
     
         25 ) The method according to  claim 1 , wherein the one or more other therapeutic substances are selected from other antidiabetic substances. 
     
     
         26 ) The method according to  claim 1 , further comprising administering empagliflozin in combination with metformin, with linagliptin or with metformin and linagliptin. 
     
     
         27 ) The method according to  claim 1 , wherein empagliflozin is administered orally in a total daily amount of 10 mg or 25 mg. 
     
     
         28 ) The method according to  claim 1 , wherein empagliflozin is administered as a pharmaceutical composition comprising 10 mg or 25 mg of empagliflozin.