Long Term Effects of Semaglutide on Weight Management: Insights from the STEP 5 Trial Summary
- In a 2-year study on the long term effects of semaglutide (2.4 mg weekly) on weight loss, significant weight loss was observed in the semaglutide group compared to placebo. The average change in body weight from baseline to week 104 was -15.2% for the semaglutide group versus -2.6% for the placebo group. Additionally, more participants in the semaglutide group achieved weight loss of ≥5% from baseline at week 104 (77.1% vs. 34.4%).
- There was a weight loss plateau at 68 weeks in which subjects maintained weight. While most of those on semaglutide experienced weight loss, a small percentage did gain weight over time, in contrast to the notably higher weight gain observed in the placebo group.
- The study also reported gastrointestinal issues as the most prevalent side effects, affecting 82% of those treated with semaglutide and 54% of those receiving the placebo. These issues included symptoms like nausea, diarrhea, vomiting, and constipation.
Introduction: A New Horizon in Obesity Treatment
Obesity, a global health challenge, affects millions worldwide, leading to numerous health complications, including heart disease and diabetes mellitus. Research has consistently demonstrated the efficacy of semaglutide in promoting substantial and sustained weight loss over extended periods.
Clinical trials have shown that once-weekly subcutaneous semaglutide treatment resulted in significant reductions in body weight, with some studies reporting weight loss of approximately 5.0 kg or 11 pounds over 12 weeks. (Blundell et al., 2017) Furthermore, continued treatment with 2.4 mg of subcutaneous semaglutide led to an average weight loss of 10.6% over 20 weeks, with participants randomized to continued treatment maintaining weight loss over an additional 48 weeks. (Rubino et al., 2021) These findings indicate the potential of semaglutide for long term effects of semaglutide for chronic weight management.
Long term effects of semaglutide for over a year are lacking. A groundbreaking study titled “Two-year effects of semaglutide in adults with overweight or obesity: the STEP 5 trial” reveals some good news for the long term effects of semaglutide, a medication originally used for blood sugar control in diabetes association recommended treatments, in managing weight over 104 weeks (i.e., 2 years).
What is Semaglutide and How Does it Work?
Semaglutide is a GLP-1 agonist. GLP-1 stands for Glucagon-Like Peptide-1. It’s a natural hormone in your body that plays a role in managing blood sugar levels and appetite. GLP-1 receptor agonists, like semaglutide, are medications that mimic the action of this hormone.
How Semaglutide Works:
Blood Sugar Control: In type 2 diabetes, semaglutide helps control blood sugar levels. It does this by stimulating the pancreas to produce more insulin when blood sugar levels are high. Insulin is a hormone that helps your body use or store the sugar it gets from food. (Aroda et al., 2019) This medication has also been used by health care providers for over 15 years to treat Type 2 diabetes, showcasing its importance in the field of health care.
Slowing Down Digestion: Semaglutide also slows down the movement of food through your stomach. This slower digestion means your blood sugar levels don’t spike as quickly after eating.(Overgaard et al., 2021)
Reducing Appetite: One of the key ways semaglutide helps with weight loss is by reducing appetite. It works on areas of your brain that control hunger and cravings, making you feel fuller for longer periods. This can lead to decreased calorie intake and, consequently, weight loss.(Husain et al., 2019)
Administration: Healthcare providers usually administer semaglutide as a once-weekly injection under the skin (subcutaneously). This method of administration makes it convenient for patients to use.
At a dose of 2.4 mg once weekly, subcutaneous semaglutide was approved in the United States, Europe, the United Kingdom, and Canada for weight management in adults with overweight or obesity. This approval was based on the results from the Semaglutide Treatment Effect in People with Obesity (STEP) clinical trial program, which included the STEP 1 and 3 trials. In these trials, participants without type 2 diabetes saw average placebo-subtracted weight losses of 12.4% and 10.3%, respectively, with semaglutide 2.4 mg at week 68. (J. P. H. Wilding et al., 2021) Despite the positive findings, the long term effects of semaglutide are lacking, however, a recent trial has some positive news.
The 2-year Step 5 Trial: The Long terms Effects of Semaglutide on Weight Loss
The STEP 5 trial was a meticulously designed study the long term effects of semaglutide, comparing the effects of weekly subcutaneous injections of semaglutide 2.4 mg or a placebo. Participants, all adults who were overweight or severely obese, received behavioral intervention alongside the treatment, including counseling on diet and physical activity. The primary focus was the percentage change in body weight and achieving ≥5% weight loss at week 104. Informed consent and strict exclusion criteria ensured the integrity of the trial’s sample size.
The trial included 304 participants, predominantly female (77.6%), with an average age of 47.3 years and a mean body mass index (BMI) of 38.5 kg/m². Specifically, the study aimed to determine the effects of once-weekly subcutaneous semaglutide 2.4 mg injections, combined with behavioral intervention, on body weight and cardiometabolic risk factors for 2 years.
Long Term Effects of Semaglutide Result in Significant Weight Loss
The results were remarkable. Participants in the semaglutide treatment group, after 2 years, experienced an average mean weight loss of 15.2%, significantly more than the 2.6% in the placebo group. Additionally, 77.1% of participants in the semaglutide group achieved a weight loss of ≥5%, compared to 34.4% in the placebo group, highlighting the long term effects of semaglutide effectiveness for weight loss treatment. Semaglutide, developed by Novo Nordisk, shows promise in clinical practice for weight management.
Will You Continue to Lose Weight with Semaglutide?
A weight loss plateau was observed in the STEP 5 trial of semaglutide for weight management after approximately 68 weeks. Despite this plateau, the significant weight loss achieved was maintained for the remainder of the 104-week study period. This pattern of rapid weight loss followed by a plateau and then maintenance of the lower weight level is a common occurrence in weight loss interventions and was a notable aspect of the long-term efficacy of semaglutide observed in this study. (Garvey et al., 2022)
Long Term Effects of Semaglutide: Cardiovascular Improvements:
The STEP 5 trial of semaglutide demonstrates several positive cardiovascular benefits in participants with obesity. The key cardiovascular benefits observed included:
Reduction in Waist Circumference: There was a notable reduction in waist circumference among participants receiving semaglutide, indicating a decrease in abdominal fat, which reduces the risk of cardiovascular disease.
Lowering Blood Pressure: Participants treated with semaglutide showed reductions in systolic and diastolic blood pressure. High blood pressure is a significant risk factor for heart disease and stroke, so its reduction is an important cardiovascular benefit.
Improvement in Lipid Profile: The study reported improvements in various lipid parameters, including reductions in levels of low-density lipoprotein (LDL) cholesterol, very-low-density lipoprotein (VLDL) cholesterol, and triglycerides. Improving lipid profiles is crucial in reducing the risk of cardiovascular diseases.
Reduction in C-Reactive Protein: A decrease in C-reactive protein levels was observed, which indicates reduced inflammation in the body. Chronic inflammation is associated with an increased risk of heart disease.
Improvement in Glycemic Control: While the study primarily involved participants without diabetes, improvements in markers like glycated hemoglobin (HbA1c) and fasting plasma glucose were noted. Better glycemic control is linked to a lower risk of developing diabetes-related cardiovascular complications.
These positive benefits not only validate the long term effects of semaglutide for weight loss but also improve cardiovascular dynamics.
Addressing Safety Concerns Long Term Effects of Semaglutide
While the long term effects of semaglutide on weight loss was apparent, safety remained a priority. Approximately 82.2% of the 152 participants treated with semaglutide experienced serious adverse events, compared to about 53.9% of the 152 participants who received a placebo. In the semaglutide group, gallbladder-related disorders, including gallbladder problems, were noted in four individuals, and two cases were observed in the placebo group.
Additionally, malignant neoplasms were reported in two participants in the semaglutide group and in four participants in the placebo group. Notably, there were no reported cases of pancreatitis in either the semaglutide or placebo treatment groups. These included abdominal pain, nausea, vomiting, diarrhea, and constipation, which are common side effects of semaglutide and the GLP-1 receptor agonist class in general. (Wadden et al., 2021; John P. H. Wilding et al., 2021)
Practical Applications: A Step Forward
The implications of the STEP 5 trial extend beyond mere weight reduction. This sustained weight loss can improve various obesity-related conditions, such as cardiovascular diseases, type 2 diabetes, and joint problems, enhancing overall health and quality of life.
Conclusion: The Long Term Effects of Semaglutide: A Promising Future
The findings from the STEP 5 trial have significant practical applications. They provide healthcare professionals with a new tool for long-term weight management in individuals with obesity or overweight. This could revolutionize obesity treatment, offering a more effective and sustainable solution than existing methods
In conclusion, the STEP 5 trial presents semaglutide as a highly effective option for sustained weight management in adults with obesity or overweight. Its significant impact on weight loss and a manageable safety profile position it as a pivotal player in the battle against obesity. As we move forward, further research and clinical applications of semaglutide will undoubtedly shape the future of obesity treatment, offering new hope to millions struggling with weight issues through a combination of medical interventions and lifestyle changes.
Long Term Effects of Semaglutide: Insights from STEP 5 Trial References
Aroda, V. R., Ahmann, A. J., Cariou, B., Chow, F. C. C., Davies, M. J., Jódar, E., Mehta, R., Woo, V., & Lingvay, I. (2019). Comparative Efficacy, Safety, and Cardiovascular Outcomes With Once-Weekly Subcutaneous Semaglutide in the Treatment of Type 2 Diabetes: Insights From the SUSTAIN 1–7 Trials. Diabetes & Metabolism. https://doi.org/10.1016/j.diabet.2018.12.001
Blundell, J., Finlayson, G., Axelsen, M., Flint, A., Gibbons, C., Kvist, T., & Hjerpsted, J. (2017). Effects of Once‐weekly Semaglutide on Appetite, Energy Intake, Control of Eating, Food Preference and Body Weight in Subjects With Obesity. Diabetes Obesity and Metabolism. https://doi.org/10.1111/dom.12932
Garvey, W. T., Batterham, R. L., Bhatta, M., Buscemi, S., Christensen, L. N., Frias, J. P., Jódar, E., Kandler, K., Rigas, G., Wadden, T. A., Wharton, S., & the, S. S. G. (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
Husain, M., Birkenfeld, A. L., Donsmark, M., Dungan, K., Eliaschewitz, F. G., Franco, D. R., Jeppesen, O. K., Lingvay, I., Mosenzon, O., Pedersen, S. D., Tack, C. J., Thomsen, M. S., Vilsbøll, T., Warren, M., & Bain, S. C. (2019). Oral Semaglutide and Cardiovascular Outcomes in Patients With Type 2 Diabetes. New England Journal of Medicine. https://doi.org/10.1056/nejmoa1901118
References
Overgaard, R. V., Navarria, A., Ingwersen, S. H., Bækdal, T. A., & Kildemoes, R. J. (2021). Clinical Pharmacokinetics of Oral Semaglutide: Analyses of Data From Clinical Pharmacology Trials. Clinical Pharmacokinetics. https://doi.org/10.1007/s40262-021-01025-x
Rubino, D., Abrahamsson, N., Davies, M. J., Hesse, D., Greenway, F. L., Jensen, C., Lingvay, I., Mosenzon, O., Rosenstock, J., Rubio, M. A., Rudofsky, G., Tadayon, S., Wadden, T. A., Dicker, D., & Investigators, S. (2021). Effect of Continued Weekly Subcutaneous Semaglutide vs Placebo on Weight Loss Maintenance in Adults With Overweight or Obesity. JAMA. https://doi.org/10.1001/jama.2021.3224
Wadden, T. A., Bailey, T. S., Billings, L. K., Davies, M., Frias, J. P., Koroleva, A., Lingvay, I., O’Neil, P. M., Rubino, D. M., Skovgaard, D., Wallenstein, S. O. R., & Garvey, W. T. (2021). 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, 325(14), 1403-1413. https://doi.org/10.1001/jama.2021.1831
Wilding, J. P. H., Batterham, R. L., Calanna, S., Davies, M., Van Gaal, L. F., Lingvay, I., McGowan, B. M., Rosenstock, J., Tran, M. T. D., Wadden, T. A., Wharton, S., Yokote, K., Zeuthen, N., & Kushner, R. F. (2021). Once-Weekly Semaglutide in Adults with Overweight or Obesity. N Engl J Med, 384(11), 989-1002. https://doi.org/10.1056/NEJMoa2032183
Wilding, J. P. H., Batterham, R. L., Calanna, S., Davies, M., Van Gaal, L. F., Lingvay, I., McGowan, B. M., Rosenstock, J., Tran, M. T. D., Wadden, T. A., Wharton, S., Yokote, K., Zeuthen, N., & Kushner, R. F. (2021). Once-Weekly Semaglutide in Adults with Overweight or Obesity. New England Journal of Medicine, 384(11), 989-1002. https://doi.org/10.1056/NEJMoa2032183
Additional Information on the Long Term Effects of Semaglutide: Insights from STEP 5 Trial
The STEP 5 trial examined long term effects of semaglutide injections for obesity. The study discusses the use of semaglutide injections for weight management and their potential risks and side effects. While semaglutide has shown effectiveness in reducing weight, it’s important to be aware of possible semaglutide side effects, including stomach pain, severe nausea, and allergic reactions. Patients with a history of kidney problems should be cautious, as semaglutide can exacerbate kidney disease, potentially leading to kidney damage or acute kidney injury.
Regular monitoring of renal function is advised. Additionally, those with a history of thyroid cancer or endocrine neoplasia should consult their primary care physician before starting treatment. The article emphasizes the importance of seeking medical advice for any severe symptoms or allergic reactions, including swelling of the face, commonly referred to as “Ozempic face.” Patients should store semaglutide at room temperature and follow medical guidelines for injection site care.
