Treatment of hyperinsulinemic hypoglycemia with exendin (9-39)
View Patent ↗Compositions and methods for treating hyperinsulinemic hypoglycemia, such as hyperinsulinemic hypoglycemia after bariatric surgery or gastrointestinal surgery, are provided. In some embodiments, an effective amount of the glucagon-like peptide-1 receptor antagonist exendin(9-39) is subcutaneously administered twice per day.
1. A method for treating hyperinsulinemic hypoglycemia in a patient, the method comprising subcutaneously administering to the patient in need thereof a composition comprising a therapeutically effective amount of exendin(9-39) twice-per-day (BID), wherein the therapeutically effective amount is in the range of 10-30 mg exendin(9-39), wherein the composition is administered in a single injection with an injectate volume of 0.5 ml to 1 ml.
2. The method of claim 1 , wherein the therapeutically effective amount of exendin(9-39) administered twice-per-day is selected from a dosage in the range of 10-20 mg, a dosage in the range of 10-15 mg, a dosage of 10 mg, a dosage of 15 mg, a dosage of 20 mg, and a dosage of 30 mg.
3. The method of claim 2 , further comprising administering a first daily administration in the morning and a second daily administration in the evening, and wherein the first daily administration comprising a morning injectate, the second daily administration comprises an evening injectate, and the second daily administration is at least 8 hours after the first daily administration.
4. The method of claim 3 , wherein the first daily administration is administered at a first time selected from before the morning meal, at least 1 hour before the morning meal, 60 to 90 minutes before the morning meal, and during a first period from one hour before the morning meal to one hour after the morning meal.
5. The method of claim 3 , wherein the second daily administration is administered at a second time selected from 60 to 90 minutes before the evening meal, within two hours of bedtime, during a second period from after the evening meal and to before bedtime, and from 9 to 15 hours after the morning administration.
6. The method of claim 1 , wherein the patient has previously had bariatric surgery or gastrointestinal surgery.
7. The method of claim 6 , wherein the bariatric surgery is selected from the group consisting of Roux-en-Y Gastric Bypass surgery, Vertical Sleeve Gastrectomy, placement of an endosleeve device, duodenal mucosal resurfacing, partial bypass of the duodenum, vagal nerve blockade, and pyloroplasty.
8. The method of claim 6 , wherein the gastrointestinal surgery is selected from the group consisting of gastrectomy, Nissen Fundoplication, and esophagectomy.
9. The method of claim 1 , wherein the composition is formulated with a pharmaceutically acceptable diluent or carrier and one or both of a preservative and pH adjustment agent.
10. A method for treating hyperinsulinemic hypoglycemia in a patient, the method comprising subcutaneously administering to the patient in need thereof a composition comprising a therapeutically effective amount of exendin(9-39) twice-per-day (BID), wherein the therapeutically effective amount is in the range of 10-30 mg exendin(9-39), wherein the composition is a solution or suspension that comprises exendin(9-39) at a concentration range selected from 4-20 mg/ml, 10-20 mg/ml, 8-16 mg/ml, and 13-16 mg/ml.
11. A method for treating hyperinsulinemic hypoglycemia in a patient, the method comprising subcutaneously administering to the patient in need thereof a composition comprising a therapeutically effective amount of exendin(9-39) twice-per-day (BID), wherein the therapeutically effective amount is in the range of 10-30 mg exendin(9-39), wherein administration results in a steady state plasma exendin(9-39) concentration of at least 100 ng/ml as measured by liquid chromatography-mass spectrometry.
12. A method for treating hyperinsulinemic hypoglycemia in a patient, the method comprising subcutaneously administering to the patient in need thereof a composition comprising a therapeutically effective amount of exendin(9-39) twice-per-day (BID), wherein the therapeutically effective amount is in the range of 10-30 mg exendin(9-39), wherein the therapeutically effective amount of exendin(9-39) administered twice-per-day is selected from a dosage in the range of 10-20 mg, a dosage in the range of 10-15 mg, a dosage of 10 mg, a dosage of 15 mg, a dosage of 20 mg, and a dosage of 30 mg, and wherein each of the twice-per-day administrations result in a Cmax of 100 ng/ml.
13. A method for treating hyperinsulinemic hypoglycemia in a patient, the method comprising subcutaneously administering to the patient in need thereof a composition comprising a therapeutically effective amount of exendin(9-39) twice-per-day (BID), wherein the therapeutically effective amount is in the range of 10-30 mg exendin(9-39), wherein the therapeutically effective amount of exendin(9-39) administered twice-per-day is selected from a dosage in the range of 10-20 mg, a dosage in the range of 10-15 mg, a dosage of 10 mg, a dosage of 15 mg, a dosage of 20 mg, and a dosage of 30 mg, and, wherein the amount of exendin(9-39) in the evening injectate is greater than the amount of exendin(9-39) in the morning injectate.
14. The method of claim 13 , wherein the amount of exendin(9-39) in the evening injectate is 5 mg-10 mg greater than the amount of exendin(9-39) in the morning injectate.
15. The method of claim 14 , wherein the amount of exendin(9-39) in the morning injectate is selected from 10 mg, 15 mg, and 20 mg.
16. The method of claim 13 , wherein a concentration of exendin(9-39) in the morning injectate is unequal to a concentration of exendin(9-39) in the evening injectate.
17. The method of claim 16 wherein the concentration of exendin(9-39) in the morning injectate is higher than the concentration of exendin(9-39) in the evening injectate.
18. The method of claim 13 , wherein a Tmax of the exendin(9-39) after the second daily administration is longer than a Tmax of the exendin(9-39) after the first daily administration.
19. The method of claim 18 , wherein the concentration of exendin(9-39) in the morning injectate is selected from 4-20 mg/ml, 10-20 mg/ml, 8-16 mg/ml, and 13-16 mg/ml.
20. The method of claim 18 , wherein the concentration of exendin(9-39) in the evening injectate is selected from 4-20 mg/ml, 10-20 mg/ml, 8-16 mg/ml, and 13-16 mg/ml.
21. A method for treating hyperinsulinemic hypoglycemia in a patient, the method comprising subcutaneously administering to the patient in need thereof a composition comprising a therapeutically effective amount of exendin(9-39) twice-per-day (BID), wherein the therapeutically effective amount is in the range of 10-30 mg exendin(9-39), wherein subcutaneous administration twice-per-day comprises administering a morning injectate and an evening injectate, and the amount of exendin(9-39) administered is the same in the morning and evening injectates and the concentration of exendin(9-39) is greater in the evening injectate compared to the morning injectate.
22. The method of claim 21 wherein the concentration of exendin(9-39) in morning injectate is 15 mg/ml and the concentration of exendin(9-39) in the evening injectate is 20 mg/ml.
23. A method for treating hyperinsulinemic hypoglycemia in a patient, the method comprising subcutaneously administering to the patient in need thereof a composition comprising a therapeutically effective amount of exendin(9-39) twice-per-day (BID), wherein the therapeutically effective amount is in the range of 10-30 mg exendin(9-39), wherein the composition is administered to the patient for at least 30 days.