This year at AACE, two studies were presented demonstrating liraglutide’s potential benefits in new patient populations. According to the studies, liraglutide appears to work both as an add-on to insulin in type 1 diabetes and as a weight-loss agent in nondiabetic patients.
Nitesh Kuhadiya, MD, of the University at Buffalo in New York state, and colleagues reported during a late-breaking session at the AACE meeting that in a randomized controlled trial, a 1.8-mg dose of liraglutide significantly improved both HbA1c and fasting glucose in patients with type 1 diabetes compared with placebo.
Kuhadiya and colleagues had conducted an earlier study that showed liraglutide improved glycemic control when added to insulin for type 1 diabetic patients, so they decided to do a randomized controlled trial — the first of its kind in type 1 diabetics — to assess the effects of liraglutide in type 1 diabetics.
They randomized 72 patients to placebo or to one of three doses of liraglutide — 0.6 mg, 1.2 mg, or 1.8 mg — over a 12-week period.
They found that the drug significantly improved glycemic control for patients on both of the two higher doses in terms of mean fasting glucose, with both falling by about 10 mg/dL (P<0.05) — but the drop in HbA1c was only significant for those in the 1.2-mg group, they reported (-0.8%, P<0.05).
A significant increase in time spent in good glycemic control, however, was only significant for those in the 1.8-mg group, they reported — but the time spent in hyperglycemia (160 to 240 mg/dL) and at extreme hyperglycemia (240 mg/dL and above) was reduced in both the 1.2-mg and 1.8-mg groups, they found.
Both groups also spent significantly less time in hypoglycemia (below 55 mg/dL), the investigators reported, and both groups had a significant reduction in insulin dose.
Significant weight reductions were seen for all patients on the drug, even those on the lowest dose of liraglutide (0.6 mg), the researchers said.
From the results it was concluded that the research group’s findings "have significant implications for the future treatment of type 1 diabetes."
SCALE Study Demonstrates Clinically Meaningful Weight Loss
For the SCALE study — the top-line results of which were reported last year — obese patients with and without prediabetes were randomized to placebo or to 3 mg of liraglutide — a dose higher than the highest doses used in type 2 diabetes — and followed for 56 weeks to assess the effects on inducing and maintaining weight loss.
All of the patients had failed earlier attempts to lose weight with diet and exercise.
According to data from the SCALE study, nondiabetic patients had significantly greater mean weight loss with liraglutide compared with those on placebo (-8% versus -2.6%). Xavier Pi-Sunyer, MD, of Columbia University Medical Center in New York City, said during an oral presentation session that even though the obesity trial used a larger dose of liraglutide than that used in diabetes, there was still "very good safety data … and beneficial effects on HbA1c, blood pressure, and lipids, so the net effect was very positive and I think this will be a very significant trial."
Pi-Sunyer and colleagues reported significant reductions in weight with high-dose liraglutide compared with placebo, with a mean loss of 8% of body weight for those on the drug compared with a loss of just 2.6% for those on placebo.
More patients also achieved 5% and 10% weight loss with drug compared with placebo, the researchers found.
They also had greater improvements in waist circumference, body mass index (BMI), fasting plasma glucose, HbA1c, blood pressure, and lipids than did those on placebo, Pi-Sunyer said.
At the same time, the drug’s safety profile was generally consistent with that observed in previous trials, even though it was given at a much higher dose, the researchers noted. The most common adverse events were nausea, diarrhea, and constipation.
There was also a slightly higher incidence of gallbladder issues with the drug (2.7 events per 100 versus 1.0 per 100), as well as more acute pancreatitis (0.3 events per 100 versus 0.1 events per 100), although the overall incidence was low, the researchers noted.
They said the imbalance regarding these two effects is undergoing further investigation.
- In a randomized trial, addition of liraglutide to insulin significantly reduced hemoglobin A1c (HbA1c) and body weight in type 1 diabetes patients.
- In another study, higher doses of liraglutide were associated with significant weight loss in nondiabetic obese patients
- Note that this data and conclusions should be considered to be preliminary until published in a peer-reviewed journal.
American Association of Clinical Endocrinologists: Kuhadiya N, et al "Liraglutide as additional treatment to insulin in patients with type 1 diabetes mellitus: a randomized clinical trial" AACE 2014; Abstract 1995119.