Obesity has been a global health concern for several decades, affecting over 650 million adults and contributing to significant health risks, including cardiovascular disease, diabetes, and hypertension. Managing obesity requires long-term solutions, often combining diet, exercise, and behavioral changes. Yet, for many individuals, these approaches alone do not result in sustainable weight loss. Recently, semaglutide, a glucagon-like peptide-1 (GLP-1) receptor agonist, more well-known through the product name Wegovy has emerged as a promising treatment to support weight management alongside lifestyle interventions. Two significant studies – the STEP (Semaglutide Treatment Effect in People with obesity) trials – highlight the effectiveness and safety of semaglutide in achieving weight loss, demonstrating its potential as a valuable tool for managing obesity.
Semaglutide Action Mechanisms
Semaglutide acts on the GLP-1 hormone system, which plays a role in regulating appetite and insulin release. GLP-1 receptor agonists like semaglutide bind to specific receptors in the pancreas, brain, and other organs, enhancing insulin release when blood glucose levels are high and reducing the secretion of glucagon, a hormone that raises blood sugar. By slowing gastric emptying and promoting satiety, semaglutide helps individuals consume fewer calories without feeling hungry. Unlike traditional dietary approaches, semaglutide offers a pharmacological mechanism to address hunger and regulate food intake, supporting individuals in their weight loss process.
The STEP Trials: Two-Year Results
The STEP 5 trial, a part of the extensive clinical STEP program, examined the effects of semaglutide over a 104-week period in adults with obesity or overweight. In this randomized, placebo-controlled study, 304 participants were assigned either 2.4 mg of semaglutide weekly or a placebo, combined with lifestyle interventions. The primary goals were to assess the percentage of body weight loss and whether participants achieved a minimum of 5% weight loss from their baseline weight. The results were significant: participants on semaglutide lost an average of 15.2% of their baseline weight, compared to just 2.6% in the placebo group (Garvey et al.).
Beyond weight loss, semaglutide led to improvements in cardiometabolic health. Participants experienced reductions in waist circumference, blood pressure, and key markers like fasting blood glucose and cholesterol. Such improvements highlight semaglutide’s potential to reduce risks associated with obesity, making it more than just a weight-loss medication – it may also improve overall metabolic health (Chao et al.).
Long-Term Implications of Semaglutide Use
Weight regain is a common challenge in obesity management, particularly when medications or intensive behavioral interventions are discontinued. However, the STEP 5 trial demonstrated that semaglutide could help sustain weight loss over an extended period, showing minimal weight regain after the first year. This finding underscores the importance of continued semaglutide therapy for long-term weight management and supports the need for sustained use to maintain benefits.
The STEP trials also explored the impact of semaglutide on participants’ quality of life. Significant improvements were reported in physical functioning and vitality, reflecting not only the physical benefits of weight loss but also its positive effect on daily life. Such enhancements in quality of life are crucial, as they motivate sustained treatment adherence and lifestyle improvements (Wadden et al.).
Safety and Tolerability
The safety profile of semaglutide aligns with that of other GLP-1 receptor agonists, with gastrointestinal issues being the most frequently reported side effects. While some participants experienced mild to moderate nausea, diarrhea, or constipation, these effects were generally short-lived and manageable. Less than 6% of participants discontinued the trial due to adverse events. This tolerability, combined with the effectiveness of semaglutide in producing meaningful weight loss, strengthens its case as a safe option for long-term weight management in people with obesity.
Conclusion
The STEP trials illustrate that semaglutide offers a new pathway for obesity management by leveraging the GLP-1 hormone system to reduce appetite and promote sustained weight loss. For individuals who struggle to maintain weight loss through diet and exercise alone, semaglutide provides an additional tool that not only supports weight reduction but also enhances cardiometabolic health. Although lifestyle interventions remain essential for addressing obesity, semaglutide’s efficacy and safety present it as a promising adjunct for long-term weight management. Continued research will likely provide further insights into its role in treating obesity and associated health risks.
References
Wadden, Thomas A et al. “Effect of Subcutaneous Semaglutide vs Placebo as an Adjunct to Intensive Behavioral Therapy on Body Weight in Adults With Overweight or Obesity: The STEP 3 Randomized Clinical Trial.” JAMA vol. 325,14 (2021): 1403-1413. doi:10.1001/jama.2021.1831
Weghuber, Daniel et al. “Once-Weekly Semaglutide in Adolescents with Obesity.” The New England journal of medicine vol. 387,24 (2022): 2245-2257. doi:10.1056/NEJMoa2208601 Garvey, W Timothy et al. “Two-year effects of semaglutide in adults with overweight or obesity: the STEP 5 trial.” Nature medicine vol. 28,10 (2022): 2083-2091. doi:10.1038/s41591-022-02026-4
Chao, Ariana M et al. “Semaglutide for the treatment of obesity.” Trends in cardiovascular medicine vol. 33,3 (2023): 159-166. doi:10.1016/j.tcm.2021.12.008
Blundell, John et al. “Effects of once-weekly semaglutide on appetite, energy intake, control of eating, food preference and body weight in subjects with obesity.” Diabetes, obesity & metabolism vol. 19,9 (2017): 1242-1251. doi:10.1111/dom.12932
By. Hayoung Kim