Obesity presents a leading public health concern in not just the U.S. but around the world. As several drugs supporting weight loss became associated with severe repercussions for its users, new pharmaceuticals for weight management are desperately needed. A recent study was the first to evaluate the efficacy and safety of semaglutide, the glucagon-like peptide-1 (GLP-1) analogue, in comparison to liraglutide and a placebo, in terms of weight loss.
Understanding the complexities of obesity
More than just being a cosmetic concern, obesity is a complex disorder involving an excessive amount of body fat. As major health institutions now characterize obesity as a chronic disease, it indicates the multifaceted nature of this disorder involving many genetic, physiological, behavioral and cultural aspects.
Being obese brings with it an array of associated metabolic, mechanical and mental health disorders alongside a greater risk of cardiovascular disease and certain cancers. Diabetes, high blood pressure, and orthopedic complications are some of the leading ailments associated with obesity.
Even though a weight loss of 5 to 10 percent of body mass reduces complications accompanying obesity and improves quality of life, this goal can be very difficult to achieve and sustain. Drugs to assist and maintain weight loss have existed as early as the 1930s, yet many have been associated with severe cardiotoxicity, psychiatric disorders, and dependency, and have subsequently been withdrawn from global and regional markets.
Liraglutide and semaglutide
There remain available better tolerated agents comprising of five compounds presently approved for weight management in the U.S. and three in Europe. One such compound is liraglutide, a hormone regulator of insulin and glucagon release that helps reduce appetite and modulate energy intake.
It was initially approved for treatment of type 2 diabetes at a subcutaneous dose of 1.2 mg or 1.8 mg daily. It was eventually approved in several countries for weight management at a higher dose of 3 mg per day, in combination with dietary and exercise interventions.
Semaglutide is a longer acting GLP-1 analogue approved for use in type 2 diabetes only but has also shown efficacy for the promotion of weight loss in previous studies. This study compares semaglutide with liraglutide to determine which compound offers more significant weight loss and safety parameters.
Present study
The team conducted a randomized, double-blind phase 2 trial conducted in 8 countries involving 71 clinical sites. Participants included 957 adults with no diagnosis of diabetes and a BMI at or above 30 kg/m2.
Each participant was required to have undergone one previous non-surgical weight loss attempt. These participants were randomly assigned to either the semaglutide treatment group, liraglutide group, or a placebo group.
The study was comprised of a week-long screening period, 52 weeks of treatment and a post-treatment follow-up of 7 weeks.
Subcutaneous injections were given on a daily basis for 52 weeks. Initial dose of semaglutide was 0.05 mg/ day and increased every four weeks to a target dose of either 0.05 mg, 0.1 mg, 0.2 mg, 0.3 mg, or 0.4 mg. Liraglutide initial dose was 0.6 mg/day and increased weekly to a target dose of 3 mg daily. Participants were provided predetermined caloric intake limits and assessed every four weeks for adherence. Labs were also drawn approximately every 12 weeks.
Fluctuations in body weight percentages were utilized to determine the efficacy of these drugs. Physical and nutritional counseling was provided every four weeks. Results showed all treatments groups underwent weight reduction percentages more significant than that in the placebo group.
Results included:
- Eighty-three percent of those treated with 0.4 mg of semaglutide lost at least 5 percent of body weight, compared with 23 percent of participants receiving placebo and 66 percent of those taking 3 mg of liraglutide.
- Patients treated with 0.4 mg of semaglutide lost an average of 13.8 percent of body weight at 52 weeks, compared with 2.3 percent in the placebo group and 7.8 percent among participants taking 3 mg of liraglutide.
- Patients receiving lower target doses of semaglutide still saw significant weight loss at 52 weeks: those taking 0.05 mg lost 6 percent, those at 0.1 mg lost 8.6 percent, participants at 0.2 mg dose lost 11.6 percent and those at 3 mg dose lost 11.2 percent of weight.
Greater efficacy of semaglutide
Semaglutide, combined with diet and exercise interventions, lead to dose-dependent, clinically relevant weight losses over the course of 52 weeks that were significantly greater than placebo at all tested doses and higher than liraglutide at doses of 0.2 mg per day or more.
Weight loss in participants receiving semaglutide treatment was primarily due to the suppression of appetite and enhanced satiety. Weekly reductions of both fat and lean mass were observed, with fat loss being almost three times greater than lean mass.
Even though higher doses of semaglutide resulted in more significant weight reduction, accompanying adverse events also increased at higher doses.
Ninety percent of semaglutide participants who received the lower dose of 0.05mg daily had more than one adverse event compared to 96 percent of those receiving semaglutide 0.4mg daily.
Most common adverse events were nausea, diarrhea, constipation, nasopharyngitis, vomiting, decreased appetite, headache, and eructation. Eighty-eight percent of the liraglutide group experienced more than one adverse event compared to 79 percent belonging to the placebo group.
Findings from these studies hold particular importance for the future treatment of obesity, as treatment options still remain relatively limited. The rise in obesity among children in the U.S. is particularly concerning and it is even more imperative to find long-term solutions to this escalating, yet unchecked, health concern.
“In the US alone, more than 90 million adults have obesity. We need to continue to research and develop new therapies to support those living with this chronic disease,” Patrick M. O’Neil, Ph.D., of the Medical University of South Carolina, lead investigator of the study, said in a statement. “I am encouraged by these results and look forward to seeing data from upcoming phase 3 trials to better understand how semaglutide may play a role in the treatment of obesity.”
References:
1. https://www.mayoclinic.org/diseases-conditions/obesity/symptoms-causes/syc-20375742
2. http://www.diabetesincontrol.com/comparison-of-semaglutide-versus-liraglutide-for-weight-loss-in-patients-with-obesity/
3. https://www.ajmc.com/focus-of-the-week/semaglutide-produces-significant-sustained-weight-loss-for-adults-with-obesity-in-phase-2-trial
4. https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(18)31773-2/fulltext
About the Author:
Mark S. Gold, M.D. served as Professor, the Donald Dizney Eminent Scholar, Distinguished Professor and Chair of Psychiatry from 1990-2014. Dr Gold was the first Faculty from the College of Medicine to be selected as a University-wide Distinguished Alumni Professor and served as the 17th University of Florida’s Distinguished Alumni Professor.
Learn more about Mark S. Gold, MD
About the Transcript Editor:
A journalist and social media savvy content writer with extensive research, print and on-air interview skills, Sana Ahmed has previously worked as staff writer for a renowned rehabilitation institute, a content writer for a marketing agency, an editor for a business magazine and been an on-air news broadcaster.
Sana graduated with a Bachelors in Economics and Management from London School of Economics and began a career of research and writing right after. Her recent work has largely been focused upon mental health and addiction recovery.
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Published on March 11, 2019
Reviewed by Jacquelyn Ekern, MS, LPC on March 11, 2019
Published on WeightHope.com