Liraglutide, used as an adjunct to a low-calorie diet and exercise, improved both weight loss and glycemic control in obese patients with type 2 diabetes, compared with placebo, according to results of a randomized trial published online Aug. in JAMA.
The SCALE Diabetes trial is the first study specifically designed to assess liraglutide’s efficacy of for weight loss in patients with type 2 diabetes, as well as the first study to evaluate the higher (3.0-mg) dose of the drug in this patient population, said Dr. Melanie J. Davies of the Diabetes Research Centre, University of Leicester (England) and her associates.
This trial, conducted at 126 sites in nine countries, involved 846 participants randomly assigned in a double-blind fashion to receive daily self-administered subcutaneous high-dose [3.0 mg] liraglutide (423 patients), low-dose [1.8 mg] liraglutide (211 patients), or placebo (212 patients) for 56 weeks, followed by a 16-week observation period to assess the effects of stopping treatment. All study participants were encouraged to walk briskly for 150 minutes or more per week and to follow a low-calorie diet containing 30% energy from fat, 20% from protein, and 50% from carbohydrates.
The mean body weight at baseline was roughly 106 kg. A total of 23% of patients taking high-dose liraglutide, 22% of those taking low-dose liraglutide, and 34% of the placebo group withdrew before completing the treatment phase of the study.
Mean weight loss was 6.0% of baseline weight (6.4 kg) for high-dose liraglutide and 4.7% (5.0 kg) for low-dose liraglutide, compared with 2.0% (2.2 kg) with placebo. Half of the patients taking high-dose liraglutide and 36% of those taking low-dose liraglutide lost 5% or more of their baseline weight, compared with 13.8% of patients taking placebo. Both active-treatment groups also showed significantly greater reductions in waist circumference, the investigators said ( JAMA 2015 Aug 18 [doi:10.1001/jama.2015.9676] ).
In addition, liraglutide bested placebo in glycemic control as measured by decrease in hemoglobin A1c level; in the proportion of patients achieving HbA1c targets; and in fasting plasma glucose level, fasting glucagon level, proinsulin level, and other glycemic indexes. More patients taking liraglutide than placebo were able to reduce their use of oral hypoglycemic agents. Liraglutide also improved cardiovascular measures such as systolic blood pressure, total cholesterol, triglycerides, and C-reactive protein. Furthermore, the higher dose of liraglutide significantly improved scores on two measures of health-related quality of life.
Adverse event rates were higher with liraglutide than placebo, with GI effects predominating. There were 87 hypoglycemic events per 100 patient-years of exposure to high-dose liraglutide and 95 per 100 patient-years for low-dose liraglutide, compared with 31 per 100 patient-years for placebo. Heart rate and the incidence of cardiac arrhythmias increased with use of the active drug and returned to normal after the treatment phase concluded. Similarly, serum amylase and lipase activity increased during the treatment phase and returned to baseline level afterward. The long-term clinical relevance of these effects are not yet known, and further research also is needed to assess the effects of longer-term liraglutide therapy, Dr. Davies and her associates noted.
Liraglutide (Victoza, Novo Nordisk) was approved in December 2014 as an adjunct to a reduced-calorie diet and increased physical activity in obese adults with a body mass index of 30 kg/m2 or greater and in overweight adults with a BMI of 27 kg/m2 or greater and at least one weight-related condition such as hypertension, type 2 diabetes, or dyslipidemia.
SCALE Diabetes was funded by Novo Nordisk. Dr. Davies and her coinvestigators reported ties to Novo Nordisk and numerous other pharmaceutical companies.