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Obesity is a growing worldwide epidemic that is associated with multiple chronic health conditions. Newer options for treating obesity have become available over the past few years, and more people are considering these medications as part of their weight loss journey.
Semaglutide is one of the more widely discussed medications in this category. While it may be an option for many individuals, it may not be appropriate for everyone. This article explores what semaglutide is, how it works, and which populations should avoid using it.
What Is Semaglutide?
Semaglutide is a protein that works on the glucagon-like peptide-1 receptor. It belongs to a class of medications called glucagon-like peptide-1 (GLP-1) receptor agonists. Rybelsus® and Ozempic® are two forms of semaglutide approved by the Food and Drug Administration (FDA) for the treatment of diabetes. Wegovy® is the same medication but is approved by the FDA specifically for the treatment of obesity. [1]
Semaglutide is only available by prescription. It is also sometimes available through certain compounding pharmacies, although the medication remains under patent and is not currently available as a generic.
Rybelsus® is semaglutide in oral form, while Ozempic® and Wegovy® are typically dispensed in prefilled injection pens. Compounded semaglutide may be administered from a vial using a syringe. The prescribed dose may vary depending on the condition being treated and an individual’s response to the medication.
Wegovy® also carries an additional indication for reducing the risk of cardiovascular death, heart attack, and stroke in adults with cardiovascular disease who are overweight or obese. [2]
What Are the Effects of Semaglutide?
Semaglutide is structurally similar to glucagon-like peptides that the body produces naturally. It works at both the digestive system and brain level to slow stomach emptying, regulate insulin levels, reduce hunger and cravings, and increase feelings of fullness. [2]
Semaglutide and other GLP-1 receptor agonists are designed to last longer than naturally produced GLP-1 hormones. [3] In addition to lowering blood sugar levels, these medications have been shown to reduce the risk of death from cardiovascular disease and may also support improved kidney function. [4]
Semaglutide can also produce side effects, including[5]:
- Belching
- Bloating
- Excessive gas
- Stomach pain
- Heartburn
- Fever
- Yellowing of the skin or eyes
- Dizziness
- Headache
- Nausea and vomiting
- Shakiness
- Low blood sugars
- Diarrhea
- Constipation
- Hair loss
- Changes in taste
- Pain or skin changes at the injection site
- Fatigue
- Weakness
Rapid weight loss itself can also produce side effects. These may include reduced metabolism, muscle loss, and nutrient deficiencies. Additional potential effects include[6]:
- Loss of bone density
- Loss of strength
- Fatigue
- Hair loss
- Weakened immune function
- Nutrient deficiencies
Who Is Semaglutide Recommended For?
If you’ve been diagnosed with diabetes, the American Association of Clinical Endocrinology (AACE) recommends lifestyle interventions as the first line of treatment. If blood sugar levels remain elevated, a GLP-1 receptor agonist may be recommended depending on additional risk factors such as cardiovascular disease. [7]
Semaglutide, under the brand name Wegovy®, is approved for chronic weight management in people with a BMI of 27 or higher with at least one weight-related condition or in people with a BMI of 30 or higher.
Weight-related conditions that may qualify someone for semaglutide at a BMI under 30 include[8]:
- High blood pressure
- Type 2 diabetes
- High cholesterol
- Obstructive sleep apnea
Who Should Not Take Semaglutide According to Current Guidelines?
Like any medication, semaglutide is not appropriate for everyone. You should always discuss potential risks and benefits with a healthcare provider. Current clinical guidelines identify several populations for whom semaglutide may be contraindicated.
People With Medullary Thyroid Carcinoma (MTC) or Multiple Endocrine Neoplasia Syndrome Type 2 (MEN2)
Semaglutide and other GLP-1 receptor agonists are contraindicated in people with MTC or MEN2. Rodent studies during drug development showed an increased risk of thyroid tumors, although similar findings have not been observed in humans. [9]
People With Allergies to Semaglutide
A known allergy or sensitivity to semaglutide or its components is another reason to avoid this medication. Because semaglutide is a protein-based medication, the body may develop an immune reaction in rare cases. [9]
People Who Are Pregnant
Semaglutide should not be used during pregnancy. Animal studies have suggested potential risks including birth defects and pregnancy loss, although adequate human studies are lacking. The FDA recommends discontinuing GLP-1 medications at least two months before a planned pregnancy. [10]
People With Pancreatic Diseases
People with a history of pancreatitis or pancreatic cancer should avoid GLP-1 receptor agonists. Although the evidence is mixed, these medications may increase pancreatitis risk in some individuals. [9]
People With Acute Gallbladder Disease
GLP-1 medications may increase the risk of gallstones, partly due to rapid weight loss and possible changes in gallbladder motility. Individuals who develop symptoms of gallbladder disease should consult their healthcare provider before continuing treatment. [9]
People With Suicidal Behavior
Some research suggests that weight loss medications may be associated with increased suicidal thoughts in certain individuals. Although data are mixed, caution is recommended for people with a history of suicidal ideation or suicide attempts. [4]
Other Contraindications
Semaglutide is generally not recommended for individuals with type 1 diabetes, those already using other weight loss medications, or those with severe delayed gastric emptying. Patients who have undergone bariatric surgery may require close monitoring if GLP-1 medications are used. [4]
Alternatives to Semaglutide
Several alternatives to semaglutide exist for both diabetes management and weight management. A healthcare provider can help determine the best treatment approach for an individual’s medical history and goals.
Diabetes medication alternatives include metformin, sulfonylureas, TZDs, alpha-glucosidase inhibitors, bile acid sequestrants, SGLT2 inhibitors, DPP-4 inhibitors, and dopamine-2 agonists. [11,12]
Weight loss alternatives may include other GLP-1 receptor agonists such as liraglutide, as well as medications like phentermine-topiramate, bupropion-naltrexone, orlistat, or setmelanotide. [13]
Lifestyle Changes To Support Weight Goals
Lifestyle changes remain a key component of long-term weight management. Approaches such as healthy eating patterns and regular physical activity can help support sustainable weight loss and metabolic health. [14]
Explore Medical Weight Loss Support
Obesity is a chronic condition that often requires a comprehensive approach combining medical care, lifestyle strategies, and ongoing support.
Online telehealth programs, such as our partner Shed’s, make it easier to connect with clinicians who specialize in weight management and can help determine whether prescription treatments or other approaches may be appropriate.
References
- Research C for DEA. Medications containing semaglutide marketed for type 2 diabetes or weight loss. US Food and Drug Administration. Last reviewed January 10, 2024. Accessed September 4, 2024. Medical Citation URL.
- Office of the Commissioner. FDA approves first treatment to reduce risk of serious heart problems specifically in adults with obesity or overweight. US Food and Drug Administration. Published March 8, 2024. Accessed September 4, 2024. Medical Citation URL.
- Latif W, Lambrinos KJ, Patel P, Rodriguez R. Compare and Contrast the Glucagon-Like Peptide-1 Receptor Agonists (GLP1RAs). In: StatPearls. StatPearls Publishing; February 25, 2024. Medical Citation URL.
- Kommu S, Whitfield P. Semaglutide. In: StatPearls. StatPearls Publishing; February 11, 2024. Medical Citation URL.
- Mayo Clinic. Semaglutide (subcutaneous route) side effects. Updated April 1, 2024. Accessed September 4, 2024. Medical Citation URL.
- Cleveland Clinic. Is it bad to lose weight too quickly? Published October 5, 2021. Accessed September 4, 2024. Medical Citation URL.
- Samson SL, Vellanki P, Blonde L, et al. American Association of Clinical Endocrinology consensus statement: comprehensive type 2 diabetes management algorithm - 2023 update. Endocr Pract. 2023;29(5):305-340. doi:10.1016/j.eprac.2023.02.001 Medical Citation URL.
- Canadian Agency for Drugs and Technologies in Health. Clinical review. Semaglutide (Wegovy) - NCBI Bookshelf. Published December 1, 2022. Medical Citation URL.
- Chao AM, Tronieri JS, Amaro A, Wadden TA. clinical insight on semaglutide for chronic weight management in adults: patient selection and special considerations. Drug Des Devel Ther. 2022;16:4449-4461. doi:10.2147/DDDT.S365416 Medical Citation URL.
- Ozempic. Package Insert. Novo Nordisk. Last revised October 2022. Accessed September 4, 2024. Medical Citation URL.
- American Diabetes Association. What are my options for type 2 diabetes medications? Accessed September 4, 2024. Medical Citation URL
- Cleveland Clinic. Oral diabetes medications. Last reviewed November 23, 2022. Accessed September 4, 2024. Medical Citation URL.
- Mayo Clinic Staff. Prescription weight-loss drugs. Mayo Clinic. Published October 29, 2022. Accessed September 4, 2024. Medical Citation URL.
- Centers for Disease Control and Prevention. Steps for losing weight. Published December 28, 2023. Accessed September 4, 2024. Medical Citation URL.
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