Semaglutide, CAS No. 910463-68-2
Beijing C&K Development Co., Ltd. is a high-tech enterprise focusing on biochemical research and development, headquartered in Beijing Zhongguancun Life Science Park with GMP workshops in Qinhuangdao and Ezhou.
Semaglutide is a glucagon-like peptide-1 (GLP-1) receptor agonist that has garnered significant attention for its efficacy in weight management and cardiometabolic risk reduction. Originally developed for the treatment of type 2 diabetes, semaglutide has demonstrated substantial weight loss benefits, making it a promising option for individuals with obesity or overweight conditions.
Mechanism of Action
Semaglutide mimics the action of glucagon-like peptide-1 (GLP-1), a hormone released from the L-cells of the distal small intestine and colon in response to nutrient intake. GLP-1 binds to receptors in various tissues, including pancreatic beta cells, gastric mucosa, kidneys, heart, and the hypothalamus. It stimulates insulin release, inhibits glucagon secretion, slows gastric emptying, and reduces food intake, thereby contributing to weight loss and improved glycemic control [5, 6, 7]. Unlike native GLP-1, which has a short half-life due to rapid degradation by dipeptidyl peptidase-4 (DPP-4), semaglutide is resistant to enzymatic degradation, resulting in a longer half-life and more sustained therapeutic effects [8, 9].
Clinical Efficacy
Semaglutide has shown remarkable weight loss efficacy in clinical trials. For instance, in the STEP 5 trial, a 2-year study involving adults with overweight or obesity without diabetes, participants treated with semaglutide 2.4 mg once weekly achieved a mean weight loss of 15.2% from baseline at week 104, compared to a 2.6% weight loss in the placebo group (estimated treatment difference: −12.6 percentage points; 95% CI, −15.3 to −9.8; P < 0.0001) [1]. Additionally, 77.1% of participants in the semaglutide group achieved weight loss of at least 5% from baseline at week 104, compared to 34.4% in the placebo group (odds ratio, 5.0; 95% CI, 3.0 to 8.4; P < 0.0001) [1]. These results indicate that semaglutide can lead to substantial and sustained weight loss over an extended period.
Beyond weight loss, semaglutide also improves cardiometabolic risk factors. In a study involving patients with type 2 diabetes and chronic kidney disease, semaglutide reduced the risk of major kidney disease events by 24% (hazard ratio, 0.76; 95% CI, 0.66 to 0.88; P=0.0003) and the risk of cardiovascular death by 29% (hazard ratio, 0.71; 95% CI, 0.56 to 0.89) [2]. Another study in patients with obesity-related heart failure with preserved ejection fraction and type 2 diabetes showed that semaglutide significantly improved heart failure symptoms and physical limitations, with a mean change in the Kansas City Cardiomyopathy Questionnaire clinical summary score (KCCQ-CSS) of 13.7 points compared to 6.4 points in the placebo group (estimated difference, 7.3 points; 95% CI, 4.1 to 10.4; P<0.001) [4].
Safety Profile
The safety profile of semaglutide is generally well-tolerated, with gastrointestinal adverse events being the most commonly reported, including nausea, diarrhea, vomiting, and constipation. These events are typically mild-to-moderate in severity and transient, often occurring during the initial dose escalation period [1]. In the STEP 5 trial, gastrointestinal adverse events were reported in 82.2% of participants treated with semaglutide, compared to 53.9% in the placebo group [1]. However, these events rarely led to treatment discontinuation, with only 3.9% of participants in the semaglutide group discontinuing treatment due to gastrointestinal adverse events [1].
References
- Garvey, W. T., et al. (2022). Two-year effects of semaglutide in adults with overweight or obesity: the STEP 5 trial. Nature Medicine, 28(10), 2083–2091. https://doi.org/10.1038/s41591-022-02026-4
- Effects of Semaglutide on Chronic Kidney Disease in Patients with Type 2 Diabetes. (2024). The New England Journal of Medicine, 391(2), 109-121. https://doi.org/10.1056/NEJMoa2403347
- Semaglutide for the treatment of obesity. (2023). Trends in Cardiovascular Medicine, 33(3), 159-166. https://doi.org/10.1016/j.tcm.2021.12.008
- Semaglutide in Patients with Obesity-Related Heart Failure and Type 2 Diabetes. (2024). The New England Journal of Medicine, 390(13), 1394-1407. https://doi.org/10.1056/NEJMoa2313917