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The Peptide Effect
approvedWeight Loss & Diabetes

Semaglutide

Also known as: Ozempic, Wegovy, Rybelsus

Semaglutide is a GLP-1 receptor agonist approved by the FDA for type 2 diabetes (Ozempic, Rybelsus) and chronic weight management (Wegovy). It is the most widely prescribed GLP-1 medication globally and demonstrated a landmark 20% reduction in major cardiovascular events in the SELECT trial, establishing it as the first anti-obesity drug with proven cardiovascular benefit.

Key Facts

Mechanism
Semaglutide is a selective glucagon-like peptide-1 (GLP-1) receptor agonist with 94% structural homology to native human GLP-1. It reduces appetite through direct action on GLP-1 receptors in the hypothalamus and brainstem, slows gastric emptying to prolong satiety, enhances glucose-dependent insulin secretion from pancreatic beta cells, and suppresses inappropriate glucagon release. Its long half-life is achieved through albumin binding and resistance to DPP-4 degradation.
Research Status
approved
Half-Life
~7 days (approximately 1 week)
Molecular Formula
C₁₈₇H₂₉₁N₄₅O₅₉
Primary Use
Weight Loss & Diabetes

Benefits

  • Weight loss of 15-17% body weight at the 2.4 mg dose (STEP trials)strong
  • Robust glycemic control with HbA1c reductions of 1.5-1.8% (SUSTAIN program)strong
  • 20% reduction in major adverse cardiovascular events — heart attack, stroke, cardiovascular death (SELECT trial)strong
  • Available in oral formulation (Rybelsus) for needle-averse patientsstrong
  • Reduction in liver fat and potential MASH/NAFLD treatment benefitsmoderate
  • Potential reduction in addictive behaviors (alcohol, nicotine) based on emerging datapreliminary

Dosage Protocols

RouteDosage RangeFrequencyNotes
Subcutaneous injection (Ozempic — T2D)0.25 mg → 0.5 mg → 1 mg → 2 mgOnce weeklyStart at 0.25 mg for 4 weeks (initiation dose, not therapeutic), then escalate every 4 weeks. Maximum dose 2 mg weekly.
Subcutaneous injection (Wegovy — weight management)0.25 mg → 0.5 mg → 1 mg → 1.7 mg → 2.4 mgOnce weeklyEscalation over 16-20 weeks to reach maintenance dose of 2.4 mg. FDA approved for BMI ≥30 or ≥27 with weight-related comorbidity.
Oral tablet (Rybelsus — T2D)3 mg → 7 mg → 14 mgOnce dailyMust be taken on an empty stomach with no more than 4 oz of plain water, at least 30 minutes before first food, drink, or other oral medications. Bioavailability is ~1% due to oral absorption challenges.

Medical disclaimer

Dosage information is provided for educational reference only. Always follow your prescriber's instructions and consult a qualified healthcare provider before starting any peptide protocol.

Side Effects

  • Nausea, particularly during dose escalationcommon
  • Diarrhea and constipationcommon
  • Vomitingcommon
  • Abdominal pain and dyspepsiacommon
  • Pancreatitis (acute pancreatic inflammation)serious
  • Thyroid C-cell tumors in rodent studies — boxed warning for medullary thyroid carcinoma riskserious
  • Gallbladder disease including gallstonesrare
  • Injection site reactions (injectable formulations)common

Frequently Asked Questions

What is the difference between Ozempic and Wegovy?
Ozempic and Wegovy contain the same active ingredient (semaglutide) but are FDA-approved for different indications. Ozempic (max 2 mg/week) is approved for type 2 diabetes, while Wegovy (max 2.4 mg/week) is approved for chronic weight management. Wegovy reaches a higher maximum dose and has specific approval for obesity treatment. They cannot be used together. Your healthcare provider will prescribe the appropriate formulation based on your diagnosis.
Is oral semaglutide (Rybelsus) as effective as the injection?
Oral semaglutide (Rybelsus) is FDA-approved for type 2 diabetes but achieves lower systemic exposure than injectable forms. The oral 14 mg dose is roughly comparable to the injectable 0.5 mg dose in glycemic efficacy. It has not been approved for weight loss at current oral doses. Higher oral doses (25-50 mg) are under investigation for weight management. The injection remains the preferred route for maximum weight loss efficacy.
What is "Ozempic face" and how can I prevent it?
Ozempic face refers to facial volume loss (hollowed cheeks, sagging skin) that can occur with rapid, significant weight loss from GLP-1 medications. It is not unique to semaglutide and can happen with any substantial weight loss. Strategies to minimize it include gradual weight loss, adequate protein intake (1.0-1.2 g/kg daily), resistance training to preserve lean mass, and staying hydrated. Dermal fillers can address volume loss cosmetically. Discuss concerns with your prescribing physician.
Is there still a semaglutide shortage?
Semaglutide supply has stabilized since the severe shortages of 2023-2024. Novo Nordisk has significantly expanded manufacturing capacity. However, intermittent supply disruptions may still occur for certain dose strengths or pen configurations depending on your pharmacy and region. Check the FDA Drug Shortage Database for the most current status. Your provider may need to adjust your dose or timing temporarily if specific strengths are unavailable.
When will generic semaglutide be available?
Novo Nordisk holds patents on semaglutide extending into the 2030s. Generic versions are not expected to reach the US market before 2031-2032 at the earliest. However, compounded semaglutide has been available through some pharmacies during shortage periods, and biosimilar development is underway by multiple manufacturers. Patent litigation and regulatory pathways may affect the exact timeline. This information is not legal or financial advice.

References

  1. 1
    Once-weekly semaglutide in adults with overweight or obesity (STEP 1)(2021)PubMed ↗
  2. 2
    Semaglutide and cardiovascular outcomes in patients with obesity (SELECT trial)(2023)PubMed ↗
  3. 3
    Oral semaglutide versus subcutaneous liraglutide in type 2 diabetes (PIONEER 4)(2019)PubMed ↗
  4. 4
    Two-year effects of semaglutide in adults with overweight or obesity (STEP 5)(2022)PubMed ↗

Last updated: 2026-02-14