Expected Weight Loss on Semaglutide
Data and Resources from the New England Journal of Medicine, Yokote et. al, and IVíM Health
Summary: Semaglutide is an FDA approved treatment for weight loss and received its FDA approval through the STEP trials. Research has shown average weight loss over the course of one year is 14.9% of total body weight with more than ⅓ of patients losing >20% of total body weight (see below for details). While side effects may occur, less than 5% of patients discontinue therapy. Overall, more than 90% of patients experience weight loss success while on semaglutide therapy compared to <10% on diet and exercise alone. published
Semaglutide: What is it and how does it work? Semaglutide is a novel medication in the class of glucagon-like peptides (GLP-1’s). This medication has revolutionized the weight loss industry with an average weight loss of 14.9%, making it the most effective FDA approved treatment for weight loss therapies. Semaglutide and other medications in this class mimic the natural peptide (a sequence of amino acids forming a protein) of GLP-1, making them “analogs” of the protein. This means that they exert their effect in the same pathways GLP-1, a naturally occurring peptide, acts on our mind and bodies. Glucagon-like peptide is a hormone that is released after you ingest a meal. This peptide helps to aid your body in preparing for digestion and acts as a switch for telling your body you’ve had enough to eat. There are several mechanisms by which GLP-1 medications act to improve weight loss results. These include the following:
- Delay of gastric emptying (increased feelings of fullness)
- Slowing of gastrointestinal motility (increased feelings of fullness)
- Suppression of appetite control centers in the brain (decreased appetite)
- Amplification of glucose-dependent insulin release (decreased insulin resistance)
- Reduction of glucagon release (decreased insulin resistance)
Insulin and glucagon are two hormones that control sugar levels within the body and maintain them in a specified range. For this reason, GLP-1 medications are commonly used for diabetes management and aid in decreasing insulin resistance. This is one of the primary mechanisms by which GLP-1 medications assist with weight loss and is a large reason why weight loss results of these medications tend to improve upon predecessors of FDA approved weight loss medications.
Perhaps just as important is the side effect profile of GLP-1 medications is far safer compared to other weight loss medications commonly used. Medications like Phentermine (Adipex), Naltrexone-Buproprion (Contrave), and Phentermine-Topiramate (Qsymia) all can provide effective weight loss solutions, but they are often poorly tolerated and can cause heart and blood pressure issues. Because of this, many of these are controlled substances due to their dangerous side effect profile. The main side effects of concern on GLP-1 medications mainly lie in their effects on the gastrointestinal system (see Side Effects of Semaglutide for more). However, because this medication mimics the effects of a naturally occurring protein, the side effect profile is low and side effects are generally well tolerated.
Data to support Semaglutide for weight loss: The STEP Trails Semaglutide underwent several landmark studies to acquire its FDA approval for weight loss therapies. The STEP 1 trial was a small treatment study with approximately 300 participants and was designed to show efficacy, or overall effectiveness, of the medication. This was the first trial that showed promising results in using semaglutide for weight loss therapies. The STEP 2 trial compared semaglutide dosing to assess overall effectiveness and tolerability. Patients taking semaglutide 1.0mg were compared against patients taking semaglutide 2.4mg in a study with patients being followed over the course of a year. This study helped to determine the most effective dosing regimen for patients on semaglutide therapy as increasing dose titration to 2.4mg (as opposed to the 1.0mg for the FDA approved Ozempic formulary used for Type 2 diabetes). This study showed a superior and clinically meaningful weight loss reduction for patients taking Semaglutide at the 2.4mg dosing.
The STEP 3 trial was the major landmark trial leading to FDA approval of the medication for weight loss. This trial was featured in the New England Journal of Medicine (NEJM) and showed patients on average lost over 14.9% of their total body weight over the course of a year. Even more surprising was that over ⅓ of participants lost more than 20% of weight during this same time period. Additional data can be seen in the graphs below taken from the study. These results not only led to FDA approval of semaglutide for weight loss, but also made it the new gold standard for weight loss therapies. Finally, the STEP 4 trial was a withdrawal study to assess continued weight loss effects of patients taking semaglutide vs. patients who discontinued therapy. In this study, patients continued losing weight, an additional 7.9% on average, when continuing therapy for 68 weeks vs. only 20 weeks, thus supporting a year-long duration of therapy once a patient is optimized at the 2.4mg dosing.
Benefits of getting started on Semaglutide: The average weight loss patients experience while on semaglutide therapy is 14.9% of total body weight over the course of one year. When diving deeper into the studies, successful weight loss (defined as >5% reduction in total body weight) occurred in more than 92% of patients. Even more surprising, nearly 35% of patients lost more than 20% of their total body weight. These results have made semaglutide the most effective medication to date for obtaining successful weight loss results (see table above for expected weight loss by starting weight). In addition, patients experienced a 13 cm reduction in the waist line, a more than 5 point reduction in BMI, and also had overall reductions in their blood pressure, glycated hemoglobin (A1C), C-reactive protein (an inflammatory marker), and a decrease in lipid (cholesterol) levels. Getting started on semaglutide will provide more than just weight loss, it helps treat metabolic syndrome and may increase longevity of patients with the ability to better manage or completely avoid chronic diseases like diabetes, high cholesterol, and high blood pressure. (See more in our article on “Health Benefits of Semaglutide”)
Is it right for me? Semaglutide is an FDA approved medication for non-diabetic obesity, or weight loss management. If you’re looking for the most effective weight loss medication with a safe side effect profile, semaglutide is the answer for the vast majority of patients. The medication is FDA approved for patients with a BMI > 30 or with a BMI > 27 with one or more metabolic risk factors which include high blood pressure, high cholesterol, diabetes, and other components of metabolic syndrome. While FDA indications are important, many patients outside of these parameters may still benefit from semaglutide as an off-label use for weight loss. This includes patients with a BMI > 25 without metabolic risk factors but who want to achieve a more normal, healthy weight and are focused on disease-prevention strategies. It can be difficult to obtain insurance coverage for patients in this category. While these patients often cannot get coverage for the medication, our IVíM accessibility programs help to make the medications more affordable and accessible.
Exceptions to this include patients with a family history of medullary thyroid cancer and patients with a history of pancreatic disease. Semaglutide is contraindicated for patients with a family history of thyroid cancer due to animal studies with higher rates of thyroid cancer in animals given semaglutide. While this evidence is uncertain as the animals used in the study have a GLP-1 receptor on their thyroid that humans do not possess, it is an absolute contraindication by the FDA. Similarly, patients with a history of pancreatitis were not included in the studies on semaglutide. It is unknown how GLP-1 medications affect patients with this history and thus is a relative contraindication but can be discussed with a medical provider. For more information on Semaglutide, expected weight loss results, and the STEP trials, please see:
