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 during a press conference at the annual meeting of the Endocrine Society.
Dr. Paresh Dandona
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 22 weeks of liraglutide therapy and 1 week post treatment, 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/m2. Patients had type 1 diabetes for an average of 24 years. The mean basal insulin was 24.5 U, the mean bolus was 22.5 U/day, and the mean HbA1c level was 6.6%. All but one of the patients used insulin pumps, and the remaining patient was on four or more insulin injections per day. All patients used continuous glucose monitoring.
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.
The mechanism of action is unknown. However, Dr. Varanasi hypothesized that liraglutide might decrease the concentration of glucagon secreted after meals. Another theory is that the decrease in postprandial glucose excursion might 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.
Two of the authors have significant financial relationships with several pharmaceutical companies, but not Novo Nordisk. The remaining authors, including Dr. Varanasi, reported that they have no relevant financial disclosures.