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Liraglutide Improves Glucose Control in Type 1 Diabetes


 

From the Annual Meeting of the Endocrine Society

Major Finding: Eight patients who continued liraglutide treatment for 24 weeks lost a significant amount of weight, down from a mean of 68 kg to 63.5 kg. Mean hemoglobin A1c also dropped significantly from 6.5% to 6.1%. Mean basal insulin dropped by 48%, and mean bolus dropped by 42% as well.

Data Source: A prospective study of 14 patients with type 1 diabetes; eight patients were treated for a total of 24 weeks.

Disclosures: Two of the authors have significant financial relationships with several pharmaceutical companies, but not with Novo Nordisk, the makers of liraglutide. The remaining authors, including Dr. Varanasi, reported that they have no relevant financial disclosures.

BOSTON – Use of the type 2 medication liraglutide helped control glycemic oscillations in type 1 diabetes, significantly lowered hemoglobin A1c levels, and was associated with weight loss, a small study has shown.

The net effect is not only an improvement in mean fasting and weekly glucose concentrations, but also “you have a remarkable effect on the oscillations of glucose,” seen among type 1 diabetic patients, Dr. Paresh Dandona said at the meeting.

Liraglutide (Vitoza), made by Novo Nordisk, is a glucagonlike peptide-1 (GLP-1) receptor agonist that is currently approved for use as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus. As a GLP-1 analogue, liraglutide stimulates the release of insulin in response to elevated levels of blood sugar. It also inhibits the release of glucagon following meals, slowing the rate of food absorption from the gut into the bloodstream.

At the meeting, Dr. Ajay Varanasi reported the results of a prospective study in which 14 patients (9 male) with type 1 diabetes all used liraglutide.

Treatment for six of the patients involved a 1-week pretreatment period to optimize glycemic control, 1 week of liraglutide therapy, and 1 week post treatment. Eight additional patients also had a 1-week pretreatment period, followed by a 22-week period of liraglutide therapy, and a 1-week posttreatment period, for a total of 24 weeks.

During treatment, patients were instructed to inject 0.6 mg of liraglutide subcutaneously every day. At the onset of treatment, patients were advised to reduce their basal insulin by a quarter and bolus by a third. “This was to avoid hypoglycemia,” explained Dr. Varanasi, the lead author, who is with the division of endocrinology and metabolism at the State University of New York at Buffalo. The eight patients treated for 24 weeks were advised to increase the daily dose of liraglutide to 1.2 mg after the first week and again to 1.8 mg after 2 weeks.

At baseline, the mean patient age was 40 years and the mean BMI was 24 kg/m

During the first week of treatment, despite the reduction in insulin, there was a significant reduction in mean fasting glucose and mean weekly blood glucose.

Most interestingly, said Dr. Varanasi, the mean weekly standard deviations in insulin concentrations were significantly reduced with treatment.

“Even in a reasonably well-controlled [type 1] diabetic with an HbA1c of around 7% or less, there is [usually] a massive vacillation in insulin concentrations,” observed Dr. Dandona, the principal investigator, who is chief of the division of endocrinology at the State University of New York at Buffalo.

The eight patients on longer-term therapy lost a significant amount of weight – down from a mean of 68 kg to 63.5 kg. The mean HbA1c level dropped from 6.5% to 6.1%, which also was significant. Mean basal insulin dropped by 48%, and mean bolus dropped by 42%. The decrease in mean blood glucose was significantly reduced within the 24-48 hours. “This tells us that the response is pretty quick. And the mean standard deviation values were reduced within 48 hours,” Dr. Varanasi noted.

Regarding the mechanism of action, Dr. Varanasi hypothesized that liraglutide may decrease the concentration of glucagon secreted after meals. Another theory is that the decrease in postprandial glucose excursion may be the result of slower gastric emptying, which is known to occur with liraglutide. The weight loss seen in patients on liraglutide may have also contributed to improved glycemic control.

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