Addition of Liraglutide 3 mg to Lifestyle Modification Counseling May Reduce Weight at 56 weeks in Obese Adults Without Diabetes
Resident Focus - Volume 11, Issue 1
Reference: N Engl J Med. 2015 July 2; 373:11, (level 2 [mid-level] evidence)
Obesity is an excessive weight disorder that can lead to further health conditions such as stroke, heart disease, diabetes, and some forms of cancer. According to the Centers for Disease Control and Prevention (CDC), there are more than 78.6 million adults who are obese (body mass index of ≥30), which equates to nearly one-third of the population in the United States (CDC.gov). Obtaining a healthy weight can be very difficult with lifestyle changes alone, which raises the question: does the addition of liraglutide 3 mg daily reduce weight in obese adults without diabetes more than lifestyle changes alone?
Between 2011 and 2013, 3,731 adults were enrolled in a double-blind, placebo-controlled, multi-center trial to assess the benefits of adding liraglutide, a glucagon-like peptide-1 (GLP-1) receptor agonist, to a reduced calorie diet and physical activity. The patients, predominately white females with a mean age of 45 years, all received monthly counseling on lifestyle modifications. All patients were randomly assigned to receive liraglutide titrated up to 3 mg subcutaneously once daily (n=2,487) or placebo (n=1,244). The patient population included adults who did not have type 2 diabetes and who had a body mass index (BMI) of at least 30 or a BMI of at least 27 with concurrent dyslipidemia or hypertension. The primary endpoints were the change in body weight, the percentage of patients that lost at least 5% of their initial weight, and the percentage of patients who lost greater than 10% of their initial body weight, as these reductions are reported to be associated with decreased complications due to obesity and an improved quality of life.
After 56 weeks of treatment, the liraglutide group lost an average of 5.6 kg more than the placebo group (8.4 kg vs 2.8 kg lost) which resulted in the liraglutide group losing 5.4% more than the placebo group (95% CI -5.8 to -5.0). Of the patients in the liraglutide group, 63.2% lost at least 5% of their body weight compared to 27% in the placebo group (odds ratio [OR] 4.8, 95% CI 4.1 to 5.6). In the liraglutide group, 33.1% of patients lost at least 10% of their body weight compared to 10.6% in the placebo group (OR 4.3 95% CI 3.5 to 5.3). When comparing glycemic control, fasting glucose dropped a mean of 6.9 mg/dL more in the liraglutide group compared to placebo (95% CI -7.5 to -6.3).
The most common adverse events associated with liraglutide were nausea (40.2%), diarrhea (20.9%), and constipation (20%). Serious adverse effects for both groups were low with the most common adverse effects being cholelithiasis (0.8% in liraglutide group and 0.4% in placebo) and acute cholecystitis (0.5% in liraglutide group and 0% in placebo). The liraglutide group experienced a 28% drop out rate compared to 35.6% in the placebo group. High dropout rates decrease the level of evidence and may challenge external validity. Of the patients who dropped out of the liraglutide group, 34% did so as a result of adverse events, compared to placebo at a rate of 10%.
Liraglutide’s mechanism of action is to increase insulin release and regulate appetite, which may help individuals successfully reduce total body weight and may serve to improve patient outcomes by reducing obesity-related complications and improving quality of life. Liraglutide has been shown to be effective for reducing weight, improving glycemic control, and may improve patient quality of life when used concomitantly with diet and exercise in obese patients without diabetes.
Liraglutide is FDA approved for chronic weight management in combination with reduced-calorie diet and exercise (FDA Press Release 2014 Dec 23).
Danny R. Pate is currently a third-year pharmacy student at East Tennessee State University in Johnson City, TN. His interests include evidence-based medicine, research, cardiology, and infectious disease. He currently serves as a pharmacy student tutor for the college, as well as serving on the admissions and assessment committees.
Faculty support by Kathryn A. Mueller, PharmD. and peer review by Rachel Leigh Brown, PharmD./MPH candidate.