PHARMACEUTICAL COMPOSITION, METHODS FOR TREATING AND USES THEREOF
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.