New data from the phase 3a SCALE Obesity and Prediabetes trial were presented at the International Congress of Endocrinology (ICE) and the Endocrine Society’s meeting (ENDO). In addition to a greater body-weight loss, significantly fewer people with obesity and normal blood glucose at baseline progressed to prediabetes with liraglutide 3 mg treatment (6.9%) at 56 weeks, compared with placebo (19.9%, p<0.0001). Additionally, liraglutide 3 mg treatment resulted in improvements in a wide range of cardiovascular disease risk markers, compared with placebo. Individuals in the trial with prediabetes are continuing in their randomized cohort for an additional two years.
All treatment groups followed a reduced-calorie diet and increased physical activity program. In addition to a clinically meaningful body-weight loss of 8% from baseline (vs. 2.6% with placebo, p<0.0001), people without diabetes treated with liraglutide 3 mg experienced significantly greater improvements in their blood glucose levels compared to people on placebo (HbA1c estimated treatment difference [ETD]: –0.23%, p<0.0001). Furthermore, improvements in insulin secretion and sensitivity were observed in adults treated with liraglutide 3 mg, with and without prediabetes.
“Many risk factors need to be considered in the management of obesity, as it can be associated with a number of comorbidities, including heart disease and type 2 diabetes”, said Dr. Xavier Pi-Sunyer, co-director of The New York Obesity Nutrition Research Center and lead investigator of the trial. “It’s encouraging to see the weight loss demonstrated by liraglutide 3 mg, combined with the improvements in blood glucose levels and other cardiovascular risk factors such as blood pressure and lipids.”
Results from the prediabetes group demonstrated that, at 56 weeks, people treated with liraglutide 3 mg experienced a higher rate of prediabetes reversal compared with placebo; 69.7% of people reverted to normal blood glucose levels (32.1% with placebo, p<0.0001). A greater number of people progressed to type 2 diabetes with placebo (1.3 events per 100 patient-years of exposure [PYE], n=14) compared with liraglutide 3 mg (0.2 events per 100 PYE, n=4; p=0.0003).
In the trial, treatment with liraglutide 3 mg resulted in improvements in a wide range of cardiovascular risk factors and inflammatory markers compared with placebo:
- Greater reduction in blood pressure (systolic blood pressure: ETD –2.8 mm Hg; diastolic blood pressure: ETD –0.9 mm Hg, p<0.001)
- Improvement in fasting lipids, including low-density lipoprotein cholesterol (ETD –2%, p<0.01), high-density lipoprotein cholesterol (ETD 2%, p<0.01) and triglycerides (ETD –9%, p<0.0001)
- Greater reduction in the use of blood-pressure-lowering and lipid-lowering medications
The most frequently reported side effects associated with liraglutide 3 mg treatment were gastrointestinal (nausea and diarrhea), which were mild to moderate, occurred shortly after liraglutide initiation and were transient. Side effects leading to withdrawal occurred in 9.9% of people treated with liraglutide 3 mg, which were primarily gastrointestinal, compared to 3.8% with placebo, and serious adverse events were similar across treatment groups (liraglutide 3 mg, 6.3% vs. placebo, 5.0%).
Incidences of gallbladder disorders and pancreatitis were low but higher than in placebo-treated individuals. Gallbladder-related adverse events were reported as 3.1 events per 100 PYE with liraglutide 3 mg treatment compared to 1.4 events per 100 PYE for placebo, and pancreatitis as 0.3 events per 100 PYE with liraglutide 3 mg compared to 0.1 events per 100 PYE with placebo. The mean pulse rate was 2.4 beats per minute higher with liraglutide 3 mg than with placebo. Cardiovascular events reported were similar across treatment groups, but higher in people treated with placebo (liraglutide 3 mg, 8.7% vs. placebo, 9.9%).
In December 2013, based on the results of the SCALE clinical development program, Novo Nordisk submitted a New Drug Application and a Marketing Authorization Application to the US Food and Drug Administration (FDA) and the European Medicines Agency (EMA), respectively, for liraglutide 3 mg for chronic weight management in adults who have obesity (BMI ≥30 kg/m2), or are overweight (BMI ≥27 kg/m2) with comorbidities, as an adjunct to a reduced-calorie diet and increased physical activity. These applications are under review.
Date: June 21, 2014
Source: Novo Nordisk