Semaglutide is a glucagon-like peptide (GLP-1) receptor agonist approved for the treatment of type 2 diabetes. Semaglutide was developed by Novo Nordisk in 2012 as a long-acting alternative to liraglutide. One of the advantages of semaglutide compared to liraglutide and other antidiabetic drugs is its long duration of action, so once-weekly injections are sufficient. In December 2017, the U.S. Food and Drug Administration (FDA) approved injectable semaglutide. A previous phase 2 clinical trial found that semaglutide reduced weight in patients with type 2 diabetes and obesity. The weight loss was thought to be due to reduced energy intake caused by reduced appetite in patients.
In February 2021, a clinical trial (STEP 1) evaluated the effectiveness and safety of semaglutide as an adjunct to lifestyle intervention in the treatment of patients with obesity or overweight people with cardiovascular risk factors. The results showed that semaglutide Lutide has a very good weight loss effect.
STEP 1 is a randomized controlled clinical trial conducted at 129 sites in 16 countries and regions in Asia, Europe, North and South America. The researchers recruited 1,961 overweight or obese adults (18 years or older) without diabetes who had failed to lose weight through one or more self-reported dietary approaches. Subjects were randomly assigned to the treatment group (n=1,306) and the control group (n=655) in a 2:1 ratio. The treatment group received subcutaneous injection of 2.4 mg semaglutide once a week for 68 weeks. All participants received lifestyle intervention. The primary endpoints were percent change in body weight and the proportion of participants who lost at least 5% of their body weight.
The results found that the average weight of the semaglutide group decreased by 14.9% from baseline to week 68, while the average weight of the control group decreased by 2.4%, with a treatment difference of 12.4 percentage points (P<0.001). The number and proportion of weight loss reaching 5%, 10% and 15% in the semaglutide group were 1047 (86.4%), 838 (69.1%) and 612 (50.5%) respectively, while those in the control group were respectively 182 (31.5%), 69 (12.0%) and 28 (4.9%). The average weight loss in the semaglutide group was 15.3 kg, while the average weight loss in the control group was 2.6 kg, with a treatment difference of 12.7 kg. Compared with the control group, the semaglutide group had better cardiometabolic risk factors and physical function. The improvements are even greater.
The most common adverse reactions in the semaglutide group were nausea and diarrhea, but these adverse reactions were generally transient, mild to moderate, and resolved over time. More people in the semaglutide group discontinued treatment due to gastrointestinal events than in the control group, 59 (4.5%) versus 5 (0.8%).