METHODS OF PREVENTING PROGRESSION TO TYPE 2 DIABETES MELLITUS

• US 20180055818A1
• Filed: 06/30/2017
• Published: 03/01/2018
• Est. Priority Date: 10/08/2013
• Status: Active Grant

• Current Assignee: Vivus Incorporated
• Original Assignee: Vivus Incorporated
• Inventors: DAY, Wesley, TROUPIN, Barbara
• Granted Patent: US 10,058,532 B2
• Time in Patent Office: Days
• CPC Class Codes: A61K 2300/00 Mixtures or combinations of active ingredients, wherein at least one active ingredient is fully defined in groups A61K31/00 - A61K41/00
• CPC Class Codes: A61K 31/137 Arylalkylamines, e.g. amphetamine, epinephrine, salbutamol, ephedrine or methadone
• CPC Class Codes: A61K 31/357 having two or more oxygen atoms in the same ring, e.g. crown ethers, guanadrel
• CPC Class Codes: A61K 31/7048 having oxygen as a ring hetero atom, e.g. leucoglucosan, hesperidin, erythromycin, nystatin , digitoxin or digoxin
• CPC Class Codes: A61P 3/10 for hyperglycaemia, e.g. antidiabetics

Abstract

The present invention provides compositions and methods for delaying or preventing progression to type 2 diabetes mellitus in individuals with prediabetes and metabolic syndrome.

Claims

1. A method of delaying the progression from prediabetes to diabetes in a patient, comprising[,]

(a) identifying a patient at risk for developing type 2 comprising determining that the patient has at least one of the following:

(i) HbA1c levels that are between 5.7% and 6.4%;

(ii) plasma glucose levels between 7.8 mmol/L and 11 mmol/L; and

(iii) blood glucose levels less between 6.1 mmol/L and 7.0 mmol/L; and

(b) administering to the patient an oral dosage form comprising immediate release phentermine and controlled release topiramate.

2. The method of claim 1 wherein the oral dosage form comprises:

a) 3.75 mg immediate release phentermine in combination with 23 mg controlled release topiramate, or

b) 7.5 mg immediate release phentermine in combination with 46 mg controlled release topiramate, or

c) 11.25 mg immediate release phentermine in combination with 69 mg controlled release topiramate, or

d) 15 mg immediate release phentermine in combination with 92 mg controlled release topiramate.

3. The method of claim 2 wherein the oral dosage form is administered to the patient for at least 3 months.

4. The method of claim 1 wherein a first oral dosage form is administered to the patient for 1 to 2 weeks and a second oral dosage form is administered to the patient for 3 months and wherein the first oral dosage form comprises 3.75 mg immediate release phentermine in combination with 23 mg controlled release topiramate and the second oral dosage form comprises 7.5 mg immediate release phentermine in combination with 46 mg controlled release topiramate.

6. The method of claim 1 further comprising continuing to administer the oral dosage form to the patient following the onset of type 2 diabetes and thereby reducing the severity of type 2 diabetes symptoms in the patient.

7. The method of claim 3 wherein the administering prevents the onset of type 2 diabetes in the patient for the at least 3 months.

8. The method of claim 7 wherein the onset of type 2 diabetes is prevented if the patient has at least one of the following after the at least 3 months:

(i) HbA1c levels that are 6.4% or less;

(ii) plasma glucose levels that are 11 mmol/L or less; and

(iii) blood glucose levels that are 7.0 mmol/L or less.

9. The method of claim 1 further comprising achieving in the patient at least one of the following:

lowering of hs-CRP values to less than 3.0 mg/L, lowering fibrinogen levels to at least 400 mg/dL and increasing adiponectin concentrations to a level that is higher than the level measured in the patient prior to administering the oral dosage form to the patient.

10. The method of claim 1 further comprising achieving in the patient an improvement in at least one of the following:

fasting glucose levels, fasting insulin levels, 2-hour post-OGTT glucose levels, fasting triglycerides levels or HDL-C levels.

11. The method of any one of the preceding claims, wherein the patient has MetS.

15. The method of claim 11 wherein the step of identifying a patient having MetS comprises determining that the patient has at least three of the following:

(i) waist circumference of at least 102 cm if the patient is male or at least 88 cm if the patient is female;

(ii) triglyceride level of 150 mg/dL or higher;

(iii) HDL cholesterol levels below 40 mg/dL if the patient is a male or below 50 mg/dL if the patient is a female or taking lipid lowering medication;

(iv) systolic blood pressure of 130 mm Hg or greater, or diastolic blood pressure of 85 mm Hg or greater or taking antihypertensive medication; and

(v) fasting blood glucose levels of 100 mg/dL or greater or taking medication for elevated glucose.

16. The method of claim 11 further comprising achieving in the patient at least one of the following:

lowering of hs-CRP values to less than 3.0 mg/L, lowering fibrinogen levels to at least 400 mg/dL and increasing adiponectin concentrations to a level that is higher than the level measured in the patient prior to administering the oral dosage form to the patient.

17. The method of claim 11 further comprising continuing to administer the oral dosage form to the patient following the onset of type 2 diabetes and thereby reducing the severity of type 2 diabetes symptoms following onset of diabetes in the patient.

19. The method of claim 11 wherein the patient achieves remission of MetS.

20. The method of claim 11 further comprising achieving in the patient an improvement in at least one of the following over the measurements for the patient prior to administering the oral dosage form to the patient:

fasting glucose levels, fasting insulin levels, 2-hour post-OGTT glucose levels, fasting triglycerides levels or HDL-C levels.

5. (canceled)

12-14. -14. (canceled)