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Exenatide Reduces Insulin Use in Type 2 Diabetics

Posted: Friday, July 07, 2006

Exenatide therapy results in weight loss and a substantial decrease in insulin doses in some of the most difficult-to-manage patients with type 2 diabetes.

Treatment of obese patients with type 2 diabetes who are on insulin therapy and continue to have poor glycemic control and weight gain is a clinical and therapeutic challenge," Dr. Chaudhuri said during his presentation. "We wanted to see if the appetite-suppressing, glucose-lowering, and weight-loss properties of exenatide might be useful in this population."

Dr. Chaudhuri and colleagues conducted a retrospective analysis of 28 women and 17 men who had type 2 diabetes for a mean duration of 10 years (± 4 years). All were receiving insulin therapy and insulin sensitizers. They were all also receiving statins and angiotensin-converting enzyme inhibitors, or angiotensin receptor blockers. During the course of the study, no changes were made to any medications except insulin.

At baseline, participants had a mean blood pressure of 124/77 mm Hg, a mean low-density lipoprotein cholesterol level of 69 mg/dL, and a mean high-density cholesterol level of 35 mg/dL. In spite of insulin treatment, all subjects had glycated hemoglobin (A1C) levels of more than 7%.

Participants self-administered 5 µg of exenatide subcutaneously twice daily. Three patients experienced severe nausea early in the study and did not continue therapy. Mean duration of follow-up was 26 weeks. Patients lost an average of 2 pounds per month, with a mean weight of 115.06 kg at baseline decreasing to 110.49 kg at follow-up (P < .001). "The weight loss that we saw was much greater than what is shown in published studies of exenatide, which is approximately 1 pound per month," Dr. Chaudhuri stated that, "The effect on suppression of appetite and the effect on decrease in blood glucose was seen very rapidly, within 2 to 3 days of beginning treatment," he said.

A1C decreased an average of 0.6%, from 7.79% to 7.18% (P = .003).

Triglyceride levels decreased from 154.68 mg/dL to 115.33 mg/dL (P = 0.02). C-reactive protein (CRP) levels decreased 33% from 9.88 mg/L to 5.53 mg/L (P = .002), with the decrease independent of weight loss and reduction in A1C.

"The reduction in CRP was exciting," Dr. Chaudhuri said, "because this was a group of patients who were already on all the medications that are known to have an effect on CRP." The reduction in CRP may be due to glucose lowering, a decrease in macronutrient intake, or a novel anti-inflammatory effect of exenatide, Dr. Chaudhuri said during his presentation. "It may have implications in terms of antiatherogenic effects and cardiovascular disease."

Participants receiving short-acting insulin who were treated with exenatide decreased their doses by 30% on average, from a mean of 62.1 U/day to 40.54 U/day (P < .001). Long-acting insulin doses also decreased by 10%, from a mean of 56.17 U/day to 48.89 U/day (P = .001).

Dr. Chaudhuri concluded that the study's findings show exenatide may be a safe and effective option in difficult-to-control obese subjects with type 2 diabetes. "This is a group that is a therapeutic nightmare. When they get to this stage, you don't know what else to do with them.

Source: Diabetes In Control: ENDO 2006 88th annual meeting of The Endocrine Society: Oral Abstracts Session 10-1. Presented June 24, 2006