Semaglutide and Weight Loss

SUMMARY:

Semaglutide, a peptide drug sold under the brand names Ozempic, Wegovy, and Rybelsus, has been used since 2017 for the treatment of type 2 diabetes. Semaglutide works as a glucagon-like peptide-1 (GLP-1) receptor agonist, increasing insulin secretion when glucose levels are elevated, slowing gastric emptying, and working on the brain to decrease cravings. While initially marketed and approved for the management of type 2 diabetes, the popularity of (and demand for) Ozempic and Wegovy have soared in recent months for their use in weight management. Obesity is a chronic condition influenced by environmental, hormonal, and genetic factors. To work for chronic weight management, semaglutide must be taken indefinitely. Stopping semaglutide will result in weight gain and reversal of any cardiometabolic benefits (See “Primary Sources – Learn More” below)

Clinical Actions

Most common side effects of semaglutide are gastrointestinal
- Nausea | Emesis | Diarrhea | Constipation
- Patients who lose weight quickly may develop biliary disease (e.g., biliary colic, gallstones)
- Rare side effects include: Pancreatitis | Kidney failure
Semaglutide contains a black box warning for increased risk of thyroid C-cell tumors in rodent studies
- Semaglutide use is contraindicated in patients with a personal or family history of medullary thyroid cancer or in patients with Multiple Endocrine Neoplasia syndrome type 2 (MEN 2)
There are also reports of facial aging, colloquially called “Ozempic face”, that have gained attention in media reports
- Facial aging is due to fat loss, and possibly muscle loss, from the face, leading to skin sagging
- It can be mitigated by counseling patients to continue to eat a balanced diet without excessive calorie restriction
- For many patients the benefits of weight loss will outweigh the risks of facial aging
All versions of semaglutide should be started at lower doses and titrated to max effective doses
- This helps decrease GI side effects and improves tolerance
Both injectable forms of semaglutide contain the same medication, so 1mg of Ozempic is equivalent to 1mg of Wegovy
All versions require a prescription, and there are no approved generic versions
- Unregulated compounded versions of semaglutide are being marketed online and the FDA has warned against their use (See “Primary Sources – Learn More” below)
Semaglutide should be prescribed with dietary changes and increased physical activity
Use of Ozempic and Wegovy may be limited by their out-of-pocket costs, and if prescribed for weight loss, lack of insurance coverage
- Without insurance, Ozempic can cost almost $900 a month, and Wegovy can cost $1300 a month

Ozempic

FDA-approved in 2017 for the long-term treatment of type 2 diabetes
Ozempic is also approved to reduce the risk of heart attack, stroke, or death in adults with type 2 diabetes mellitus and heart disease
Comes as a self-injectable pen in 0.5mg, 1 mg and 2mg doses
Prescribing Ozempic for weight loss is considered off label use, and it is unavailable at the 2.4mg dose recommended for effective weight loss

Wegovy

FDA-approved in 2021 for chronic weight management in adults with obesity (BMI ≥30 kg/m²), or overweight adults (BMI ≥27 kg/m²) and at least one weight related condition (e.g., diabetes, hypertension, obstructive sleep apnea)
Comes as a self-injectable pen with a goal 2.4mg dose, notably a higher dose than Ozempic
FDA-approved in 2022 for weight management in adolescents ≥12 years old
In clinical trials, and when combined with healthy eating and physical activity, Wegovy has been shown to reduce body weight by an average of 15% at 68 weeks

Rybelsus

FDA-approved in 2019 for the treatment of type 2 diabetes
Oral pill that comes in doses of 7mg and 14mg
Novo Nordisk is currently working to determine if higher doses of Rybelsus can be used for weight management, with promising results so far from a phase 3a clinical trial (See “Primary Sources – Learn More” below)

KEY POINTS:

Semaglutide, initially approved for chronic management of type 2 diabetes, is now approved for weight management in obese and certain overweight patients
Ozempic and Wegovy are the same injectable forms of semaglutide, but only Wegovy has FDA approval for weight management and comes in doses high enough to be considered effective
Studies are underway to determine if Rybelsus, an oral formulation of semaglutide, can be used in weight management

Primary Sources – Learn More

Those Weight Loss Drugs May Do a Number on Your Face

U.S. FDA: Medications Containing Semaglutide Marketed for Type 2 Diabetes or Weight Loss

Weight regain and cardiometabolic effects after withdrawal of semaglutide: The STEP 1 trial extension

JAMA: Oral Semaglutide Led to Similar Weight Loss as Injection, Company Says