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Semaglutide May Foster Significant Weight Loss in Patients with Obesity

Oct 6, 2018
Editor: Steve Freed, R.PH., CDE

Author: Clarke Powell, Pharm.D. Candidate 2019, LECOM School of Pharmacy

When combined with diet and exercise, GLP-1 medication semaglutide may foster significant weight loss compared to liraglutide and placebo, a new study finds.

Semaglutide, a glucagon-like peptide agonist (GLP-1), can promote significant weight loss in addition to diet and exercise, a new phase 2 trial has shown. Published August 2018 in The Lancet, researchers examined the efficacy and safety of semaglutide versus liraglutide, a more commonly known GLP-1, and their effects on weight loss in patients who have obesity.


GLP-1 agonists lower blood glucose levels by mimicking the hormone, glucagon-like peptide 1, which in turn allows for insulin secretion in response to elevated blood sugar levels after meals. One of the most common effects in addition to blood glucose lowering by these agents is their promotion of weight loss caused by not only suppression of appetite, but more importantly via delaying the movement of food into the small intestine. While older GLP-1 agonists such as liraglutide are known for their weight loss properties, much is still unknown about semaglutide, the newest agent in this class.

Conducting a randomized, double-blind, multi-center, phase 2 trial, researchers in this new study enrolled patients 18 years and older without diabetes but who had clinically diagnosed obesity (BMI ³30 kg/m2). Enrolled participants were randomly assigned to one of three groups: semaglutide, liraglutide, or placebo. Within the semaglutide group, participants received 0.5mg once daily at initiation, with an incremental increase every 4 weeks until reaching the final dose (0.0.5 mg, 0.1mg, 0.2mg, 0.3mg, 0.4mg). Participants in the liraglutide group received 0.06 mg once daily at initiation, escalating incrementally to the next dose every four weeks until reaching a final dose of 0.3 mg once daily. The placebo group received an equal volume injection as well as an escalation dosing schedule to match both the semaglutide and liraglutide groups.

Diet and exercise were assessed, and participants were counseled to maintain a diet of 500 kcal below their total energy expenditure in addition to a minimum of 150 minutes of any physical activity per week.

A total of 777 participants were followed and monitored throughout the study for 52 weeks, followed by post treatment follow-up for 7 weeks. Within the semaglutide group, mean weight reduction ranged from 6.0% to 13.8%, whilst participants in the liraglutide group saw an average weight loss of 7.8%. For participants in the placebo group, mean weight reduction was 2.3%. Researchers also noted that for doses of semaglutide greater than 0.1mg, participants showed significantly greater weight loss at the completion of the study than participants receiving the highest dose of liraglutide. The most common adverse event noted was gastrointestinal upset, though this did not differ significantly between semaglutide and liraglutide groups.

Overall, this study had compelling results for a population of patients with obesity without diabetes. Results from the study confirmed that treatment with semaglutide in addition to proper diet and exercise in this patient population has a significantly greater effect on weight reduction compared to other agents in its class.

As of 2016, around 93 million adults in the United States suffered from obesity, with that number rising each year. While maintaining proper diet and exercise are critical for both prevention and improvement of obesity, this study may provide sound evidence for an agent to supplement lifestyle changes. Semaglutide may still be a novel agent when it comes to both diabetes care and weight loss, but with the evidence in favor of its efficacy and safety profile, further evaluation is needed to bring this agent to mainstream therapy.

Practice Pearls:

  • Semaglutide, in combination with proper diet and exercise, showed a significant dose-related weight loss in patients with obesity and no clinical diabetes.
  • Mean weight reduction with semaglutide ranged from 6.0% to 13.8%, whereas mean weight reduction with placebo was only 2.3%.
  • Semaglutide shows a positive safety and efficacy profile, with promising evidence as an additive agent to diet and exercise for weight loss in patients with obesity.

References for “Semaglutide May Foster Significant Weight Loss in Patients with Obesity”:

Do any diabetes drugs help you lose weight? (2018, May 11). Retrieved from https://www.mayoclinic.org/diseases-conditions/type-2-diabetes/expert-answers/byetta/faq-20057955

Oneil, P. M., Birkenfeld, A. L., Mcgowan, B., Mosenzon, O., Pedersen, S. D., Wharton, S., Wilding, J. P. (2018). Efficacy and safety of semaglutide compared with liraglutide and placebo for weight loss in patients with obesity: A randomised, double-blind, placebo and active controlled, dose-ranging, phase 2 trial. The Lancet,392(10148), 637-649. doi:10.1016/s0140-6736(18)31773-2

Overweight & Obesity. (2018, August 13). Retrieved from https://www.cdc.gov/obesity/data/adult.html

Clarke Powell, Pharm.D. Candidate 2019, LECOM School of Pharmacy