What Forms of Semaglutide Are Available?

Semaglutide, a glucagon-like peptide-1 (GLP-1) receptor agonist, has become increasingly prominent in managing type 2 diabetes and obesity. Currently, semaglutide is available in two primary formulations: injectable forms—Ozempic and Wegovy—and an oral tablet known as Rybelsus. Each formulation varies in administration, dosage, and absorption characteristics, catering to different patient needs and preferences. Additionally, compounded versions of semaglutide may occasionally be encountered; however, these compounded forms carry significant regulatory and safety concerns. Understanding the distinctions among these formulations is critical, and selecting the appropriate form should always depend on medical advice and careful consideration of individual health factors.

Injectable Formulations

Ozempic vs. Wegovy

Ozempic and Wegovy, both injectable semaglutide products manufactured by Novo Nordisk, differ primarily in their FDA-approved uses. Ozempic is approved for improving blood sugar control in adults with type 2 diabetes and reducing cardiovascular risk in individuals with established cardiovascular disease. Conversely, Wegovy specifically targets chronic weight management and is approved for adults with obesity or overweight individuals with at least one weight-related comorbid condition.

Although both formulations contain the same active ingredient, their pens differ in dosage strengths and inactive ingredients. Ozempic pens are available in doses ranging from 0.25 mg up to 2 mg weekly, while Wegovy pens provide a higher maximum dose, reaching 2.4 mg weekly. These tailored dosages reflect their distinct clinical applications.

Typical Dosage and Frequency

Both Ozempic and Wegovy are administered via subcutaneous injection, typically in the abdomen, upper arm, or thigh, once weekly. Ozempic’s dosing regimen begins with 0.25 mg weekly and may gradually increase every four weeks to a maintenance range of 1–2 mg weekly, depending on patient response and tolerance. Wegovy similarly starts with a 0.25 mg weekly dose, gradually titrating upward every four weeks until reaching the maintenance dosage of 2.4 mg weekly. Clinical trials underscore the efficacy of these formulations, with Wegovy demonstrating significant weight loss outcomes, averaging about 15% body weight reduction over 68 weeks.

Oral Semaglutide (Rybelsus)

Mechanism of Absorption

Rybelsus, the oral formulation of semaglutide, employs a proprietary absorption enhancer known as sodium N-(8-[2-hydroxybenzoyl] amino) caprylate (SNAC). This technology protects the active ingredient from gastric degradation, facilitating its absorption through the gastric mucosa. Rybelsus tablets are available in multiple strengths—3 mg, 7 mg, and 14 mg—and are administered once daily. The medication must be taken on an empty stomach with no more than 4 ounces of water, and patients should wait at least 30 minutes before eating or drinking anything else to maximize absorption.

Patient Suitability and Convenience

Rybelsus provides an appealing alternative for individuals who prefer to avoid injections, offering daily convenience and portability. However, the specific administration requirements may pose challenges in adherence for some patients. Currently, Rybelsus is FDA-approved exclusively for improving glycemic control in individuals with type 2 diabetes and is not officially approved for weight management. Clinical studies indicate moderate efficacy, showing approximately a 1.0–1.5% reduction in HbA1c and around 3–5% average body weight loss among diabetic patients.

Compounded Variations and Customizations

Reasons for Compounding

During shortages of commercially available semaglutide products, some compounding pharmacies have produced customized formulations of semaglutide, often using alternative salts such as semaglutide sodium. These compounded versions emerged primarily to address supply chain disruptions and, occasionally, to offer lower-cost alternatives. However, compounded semaglutide formulations are not FDA-approved, and their quality, safety, and efficacy have not undergone rigorous regulatory evaluation. Consequently, their use is controversial and poses potential health risks for patients.

Regulatory and Quality Considerations

The U.S. Food and Drug Administration (FDA) has issued explicit warnings regarding compounded semaglutide, emphasizing significant concerns about product sterility, potency, and accurate dosing. In October 2023, the FDA clarified that compounded semaglutide must match the active ingredient found in approved products, explicitly prohibiting the use of alternative semaglutide salts, which many compounding pharmacies had utilized. Following the resolution of supply shortages, the FDA mandated that outsourcing facilities cease production of compounded semaglutide by May 2025, and traditional compounding pharmacies were required to stop by April 2025. Patients and providers should exercise extreme caution regarding compounded semaglutide, given these regulatory constraints and associated safety risks.

Patients considering semaglutide therapy should seek detailed guidance from healthcare providers, thoroughly evaluating the available FDA-approved options and carefully reviewing any compounded alternatives.

Semaglutide therapy, regardless of form, requires careful consideration of individual health conditions, lifestyle factors, and treatment goals. Injectable formulations such as Ozempic and Wegovy offer robust efficacy in managing diabetes and obesity but require weekly adherence. Alternatively, Rybelsus provides daily convenience without injections but demands strict adherence to specific administration guidelines. While compounded versions may appear attractive due to cost or availability considerations, their unregulated nature poses significant health risks and should generally be avoided unless FDA-approved formulations are unavailable.

Patients are strongly encouraged to consult healthcare providers and trusted resources, such as Novo Nordisk, the FDA, or professional medical organizations like the American Diabetes Association (ADA) and the American Association of Clinical Endocrinology (AACE), to make informed and safe decisions regarding semaglutide treatment.

Patients must collaborate closely with healthcare providers to evaluate the most suitable and safe semaglutide formulation, taking into account individual health profiles, lifestyle considerations, and treatment goals. Due diligence and professional guidance remain paramount for maximizing the therapeutic benefits and minimizing potential risks associated with semaglutide therapy.