Exenatide Therapy in Obese Patients With Type 2 Diabetes Mellitus
Exenatide Therapy in Obese Patients With Type 2 Diabetes Mellitus
Objective: To evaluate the effect of exenatide on clinical parameters in obese patients with type 2 diabetes mellitus whose hyperglycemia is not adequately controlled despite treatment with oral hypoglycemic agents and insulin.
Methods: In this retrospective analysis, clinical progress of 52 obese patients with type 2 diabetes treated with exenatide, 5 mcg twice daily, in an outpatient setting was reviewed. Treatment initiation was between September and December 2005. Mean follow-up period was 26 weeks. Thirty-eight patients took exenatide regularly (Group A); 14 patients discontinued exenatide because of insurance, personal, or economic reasons (Group B). Measurements at baseline and at follow-up included body weight; blood pressure; and levels of hemoglobin A1c (HbA1c), high-sensitivity C-reactive protein (CRP), and plasma lipids. Insulin dosage requirements were assessed.
Results: Mean body weight (± standard error of the mean) decreased by 6.46 ± 0.8 kg (P<.001) in Group A and increased by 2.4 ± 0.6 kg in Group B (P<.001). In Group A, mean HbA1c decreased by 0.6 ± 0.21% (P = .007), and the insulin dosage requirement decreased for rapid-acting and mixed insulins (P<.02). In Group A, means of the following parameters decreased: serum total cholesterol by 8.5 ± 3.3% (P = .03), triglycerides by 26 ± 7.6% (P = .01), systolic blood pressure by 9.2 ± 3.3 mm Hg (P = .02), and high-sensitivity CRP by 34 ± 14.3% (P = .05). These indices did not change in Group B.
Conclusion: Exenatide effectively treats obese patients with type 2 diabetes on insulin, leading to weight loss and reduction in levels of HbA1c, systolic blood pressure, triglycerides, and high-sensitivity CRP.
Exenatide has recently been introduced for the treatment of type 2 diabetes mellitus. It is an incretin mimetic that binds to the known glucagon-like peptide 1 receptor. Exenatide has several actions similar to those of glucagon-like peptide 1, which help to lower blood glucose concentrations. First, it augments glucose-dependent pancreatic β-cell insulin secretion. Second, it reduces the postprandial increase in glucagon by pancreatic α-cells. Third, it slows down gastric emptying, which reduces the postprandial increase in plasma glucose concentration. Fourth, it suppresses appetite and macronutrient intake through an action on the hindbrain centers for satiety and hunger. These actions result not only in reduction of fasting and postprandial glucose concentrations, but also in concomitant weight loss. This is important because treatment with all antidiabetic medications except metformin hydrochloride, which is weight neutral, is associated with weight gain rather than weight loss.
Because insulin treatment causes significant weight gain, we decided to use exenatide to treat those patients with type 2 diabetes mellitus in our practice whose hyperglycemia was not adequately controlled (hemoglobin A1c [HbA1c] level greater than 7%) despite insulin therapy. Most of these patients were overweight and had gained more weight while on insulin therapy. Such obese type 2 diabetic patients, who are treated with a combination of oral hypoglycemic agents and insulin, are the most difficult subset of type 2 diabetic patients to treat. This report describes our clinical experience with exenatide treatment in these patients. Exenatide therapy was also tried in a small subset of obese type 2 diabetic patients who were on insulin and whose HbA1c levels were less than 6.5%.
Abstract and Introduction
Abstract
Objective: To evaluate the effect of exenatide on clinical parameters in obese patients with type 2 diabetes mellitus whose hyperglycemia is not adequately controlled despite treatment with oral hypoglycemic agents and insulin.
Methods: In this retrospective analysis, clinical progress of 52 obese patients with type 2 diabetes treated with exenatide, 5 mcg twice daily, in an outpatient setting was reviewed. Treatment initiation was between September and December 2005. Mean follow-up period was 26 weeks. Thirty-eight patients took exenatide regularly (Group A); 14 patients discontinued exenatide because of insurance, personal, or economic reasons (Group B). Measurements at baseline and at follow-up included body weight; blood pressure; and levels of hemoglobin A1c (HbA1c), high-sensitivity C-reactive protein (CRP), and plasma lipids. Insulin dosage requirements were assessed.
Results: Mean body weight (± standard error of the mean) decreased by 6.46 ± 0.8 kg (P<.001) in Group A and increased by 2.4 ± 0.6 kg in Group B (P<.001). In Group A, mean HbA1c decreased by 0.6 ± 0.21% (P = .007), and the insulin dosage requirement decreased for rapid-acting and mixed insulins (P<.02). In Group A, means of the following parameters decreased: serum total cholesterol by 8.5 ± 3.3% (P = .03), triglycerides by 26 ± 7.6% (P = .01), systolic blood pressure by 9.2 ± 3.3 mm Hg (P = .02), and high-sensitivity CRP by 34 ± 14.3% (P = .05). These indices did not change in Group B.
Conclusion: Exenatide effectively treats obese patients with type 2 diabetes on insulin, leading to weight loss and reduction in levels of HbA1c, systolic blood pressure, triglycerides, and high-sensitivity CRP.
Introduction
Exenatide has recently been introduced for the treatment of type 2 diabetes mellitus. It is an incretin mimetic that binds to the known glucagon-like peptide 1 receptor. Exenatide has several actions similar to those of glucagon-like peptide 1, which help to lower blood glucose concentrations. First, it augments glucose-dependent pancreatic β-cell insulin secretion. Second, it reduces the postprandial increase in glucagon by pancreatic α-cells. Third, it slows down gastric emptying, which reduces the postprandial increase in plasma glucose concentration. Fourth, it suppresses appetite and macronutrient intake through an action on the hindbrain centers for satiety and hunger. These actions result not only in reduction of fasting and postprandial glucose concentrations, but also in concomitant weight loss. This is important because treatment with all antidiabetic medications except metformin hydrochloride, which is weight neutral, is associated with weight gain rather than weight loss.
Because insulin treatment causes significant weight gain, we decided to use exenatide to treat those patients with type 2 diabetes mellitus in our practice whose hyperglycemia was not adequately controlled (hemoglobin A1c [HbA1c] level greater than 7%) despite insulin therapy. Most of these patients were overweight and had gained more weight while on insulin therapy. Such obese type 2 diabetic patients, who are treated with a combination of oral hypoglycemic agents and insulin, are the most difficult subset of type 2 diabetic patients to treat. This report describes our clinical experience with exenatide treatment in these patients. Exenatide therapy was also tried in a small subset of obese type 2 diabetic patients who were on insulin and whose HbA1c levels were less than 6.5%.