Researchers study efficacy and safety of GLP-1 inhibitors Semaglutide versus Liraglutide on weight loss.
Obesity can cause numerous health-related issues for patients. Lifestyle weight reduction strategies are difficult to maintain and results can take time. Liraglutide is an analogue of human glucagon-like peptide-1 (GLP-1). It is a hormone regulator of insulin and glucagon release that helps reduce appetite and increase satiety. Liraglutide is FDA approved for type 2 diabetes and weight loss. Semaglutide is a longer acting GLP-1 analogue approved for use in type 2 diabetes only, but it also promotes weight loss. This study compares semaglutide with liraglutide to determine which has greater weight loss and safety parameters.
In a double blind, randomized phase II trial, 957 adults from seven countries, without diabetes, and a BMI at or above 30 kg/m2 were assigned to either the semaglutide treatment group, liraglutide group, or a placebo group. 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 target dose of 3 mg daily. Participants were given specific caloric intake limits and assessed every four weeks for adherence. Labs were also drawn approximately every 12 weeks.
This study used change in body weight percentages to determine efficacy. Data was collected using the intention-to-treat principle and an ANCOVA model was used to analyze data. Results showed all treatments groups had greater weight reduction percentages than placebo.
Semaglutide groups with doses of more than 0.1 mg had significantly more weight loss at the end of 52 weeks compared to the liraglutide group. Weight loss of 5%, 10%, 15%, or 20% from baseline was dose-dependent. Receiving 0.05-0.4 mg per day of semaglutide had a weight loss of 5% or more in 54-83% of participants. 23% of participants receiving placebo had 5% weight reduction and 66% of liraglutide participants had a 5% weight reduction. There were 19-65% of semaglutide participants who lost 10% or more body weight compared to 34% of liraglutide participants and 10% placebo group members. Estimated mean weight loss was −2.3% for the placebo group versus −6.0% (0.05 mg), −8.6% (0.1 mg), −11.6% (0.2 mg), −11.2% (0.3 mg), and −13.8% (0.4 mg) for the semaglutide groups. All weight loss in the semaglutide groups versus placebo were significant (p≤0.0010). Mean body weight reductions for 0.2 mg or more of semaglutide versus liraglutide were all significant.
Adverse events were more frequent among semaglutide participants and was dose-dependent. Ninety percent of semaglutide participants who received the lower dose of 0.05mg daily had more than one adverse event compared to 96% 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% of the placebo group. Also, there were no severe hypoglycemic episodes in either treatment group.
- Semaglutide promotes weight reduction in individuals who have obesity.
- Higher doses of semaglutide produced more weight reduction, however adverse events also increased with dose increase.
- Adverse effects from both liraglutide and semaglutide were similar and included mainly gastrointestinal-related events.
Patrick M O’Neil, Andreas L Birkenfeld, Barbara McGowan, Ofri Mosenzon, Sue D Pedersen, Sean Wharton, Charlotte Giwercman Carson, Cecilie Heerdegen Jepsen, Maria Kabisch, John P H Wilding. 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 Issue 10148 (August 2018): 637-649. https://doi.org/10.1016/S0140-6736(18)31773-2
Angela Reyes, Pharm.D. Candidate, LECOM College of Pharmacy