Semaglutide
Also known as: Ozempic, Wegovy, Rybelsus, GLP-1 receptor agonist
Semaglutide is a GLP-1 receptor agonist originally developed for type 2 diabetes management. It has gained widespread attention for its significant effects on weight loss, with clinical trials demonstrating average body weight reductions of 15-17%; making it one of the most effective pharmacological weight management agents studied.
Semaglutide is a 4,113.58 Da research peptide. Semaglutide is a GLP-1 receptor agonist originally developed for type 2 diabetes management. It has gained widespread attention for its significant effects on weight loss, with clinical trials demonstrating average body weight reductions of 15-17%; making it one of the most effective pharmacological weight management agents studied.
Also called: Ozempic, Wegovy, Rybelsus
4,113.58
Molecular Weight
Daltons
5
Strong Evidence
benefits
5
Studies Cited
peer-reviewed
500-2000
Typical Dose
mcg
Overview
Semaglutide is a long-acting glucagon-like peptide-1 (GLP-1) receptor agonist developed by Novo Nordisk. It is a 31-amino acid peptide analogue of human GLP-1 with key structural modifications that dramatically extend its half-life to approximately 7 days, enabling once-weekly dosing. These modifications include an amino acid substitution (Aib at position 8) that resists DPP-4 enzymatic degradation, and a C-18 fatty di-acid chain that promotes albumin binding for sustained circulation. Semaglutide is one of the few peptides to have achieved full FDA approval, available as Ozempic (for type 2 diabetes), Wegovy (for chronic weight management), and Rybelsus (oral formulation for diabetes). The STEP clinical trial program demonstrated unusual weight loss results, with participants losing an average of 14.9-17.4% of body weight over 68 weeks. Beyond weight and glycemic control, semaglutide has shown cardiovascular benefits, with the SELECT trial demonstrating a 20% reduction in major adverse cardiovascular events in overweight/obese adults without diabetes.
Key Takeaways: Semaglutide
- Strongest evidence supports Semaglutide for significant weight loss and type 2 diabetes management
- Research doses typically range from 500 to 2000 mcg via subcutaneous injection (once weekly)
- 5 benefits with strong evidence, 1 moderate, 0 preliminary
- Half-life: Approximately 7 days (168 hours)
- 5 cited research studies in this guide
Mechanism of Action
Semaglutide mimics the incretin hormone GLP-1, binding to GLP-1 receptors expressed throughout the body. In the pancreas, it enhances glucose-dependent insulin secretion from beta cells and suppresses glucagon release from alpha cells, improving glycemic control. Critically, these effects are glucose-dependent, insulin is only stimulated when blood glucose is elevated, reducing hypoglycemia risk. In the brain, semaglutide acts on GLP-1 receptors in the hypothalamus (arcuate nucleus, paraventricular nucleus) and brainstem (area postrema, nucleus tractus solitarius) to reduce appetite and increase satiety signals. This central mechanism is primarily responsible for the dramatic weight loss effects. The peptide also slows gastric emptying, extending the feeling of fullness after meals. In the cardiovascular system, GLP-1 receptor activation appears to reduce inflammation, improve endothelial function, and decrease atherosclerotic plaque formation. The 7-day half-life is achieved through albumin binding via its fatty acid side chain, which protects against enzymatic degradation and reduces renal clearance. The oral formulation (Rybelsus) uses a co-formulated absorption enhancer called SNAC (sodium N-[8-(2-hydroxybenzoyl)amino]caprylate) to facilitate gastric absorption.
Research Benefits
Semaglutide at a Glance
Semaglutide mimics the incretin hormone GLP-1, binding to GLP-1 receptors expressed throughout the body.
Significant Weight Loss
Strong EvidenceThe STEP trial program (N=4,500+) demonstrated 14.9-17.4% body weight reduction over 68 weeks at the 2.4 mg weekly dose. This exceeds any previously available pharmacological weight management agent.
Type 2 Diabetes Management
Strong EvidenceMultiple Phase III trials (SUSTAIN program) showed HbA1c reductions of 1.5-1.8% and superior glycemic control compared to other diabetes medications including insulin glargine, sitagliptin, and dulaglutide.
Cardiovascular Risk Reduction
Strong EvidenceThe SELECT trial (N=17,604) demonstrated a 20% reduction in major adverse cardiovascular events (heart attack, stroke, cardiovascular death) in overweight/obese adults without diabetes treated with semaglutide 2.4 mg.
Blood Pressure Reduction
Strong EvidenceClinical trials consistently show reductions in systolic blood pressure of 3-6 mmHg with semaglutide treatment, independent of weight loss. This contributes to overall cardiovascular benefit.
Lipid Profile Improvement
Strong EvidenceStudies demonstrate reductions in triglycerides, total cholesterol, and LDL cholesterol, with improvements in HDL cholesterol. These changes exceed what would be expected from weight loss alone.
NAFLD / NASH Improvement
Moderate EvidencePreliminary studies and post-hoc analyses suggest semaglutide improves non-alcoholic fatty liver disease markers, with reductions in liver fat content, liver enzymes, and potentially liver fibrosis. Phase II data is promising.
Research Dosing Protocols
Research Purposes Only: All content is for informational and research purposes only. This site does not provide medical advice, diagnosis, or treatment. Consult a qualified healthcare professional before using any peptide or supplement.
| Research Protocol | Dose Range | Route |
|---|---|---|
| Diabetes management (Ozempic) | 500–2000 mcg | Subcutaneous injection (once weekly) |
| Weight management (Wegovy) | 250–2400 mcg | Subcutaneous injection (once weekly, escalating) |
| Oral formulation (Rybelsus) | 3000–14000 mcg | Oral tablet (daily) |
Frequency
Once weekly (injectable) / Once daily (oral)
Timing
Injectable: any time of day, same day each week. Oral: 30 min before first food/drink with ≤4 oz plain water.
Cycle Length
Ongoing — FDA-approved for chronic use. Weight regain is common upon discontinuation.
Research Notes
- 1Wegovy uses a 16-week dose escalation: 0.25 mg → 0.5 mg → 1.0 mg → 1.7 mg → 2.4 mg (each step 4 weeks).
- 2Dose escalation is critical to minimize GI side effects, do not skip to maintenance dose.
- 3The oral formulation (Rybelsus) must be taken on an empty stomach with minimal water for absorption.
- 4Weight regain of ~2/3 of lost weight has been observed within 1 year of discontinuation in clinical trials.
- 5Semaglutide is FDA-approved and available by prescription; it is not a research-only compound.
- 6Compounded versions exist but lack the quality controls of branded products.
Reconstitution Guide
Standard Reconstitution
Vial Size
5 mg
Bacteriostatic Water
2 mL
Concentration
25 mcg
per 0.1 mL (10 units)
Step-by-Step Guide
Gather Materials
Semaglutide vial, bacteriostatic water, alcohol swabs, insulin syringes.
Equilibrate Temperature
Remove the vial from storage and allow it to reach room temperature (5-10 minutes).
Sanitize
Swab the rubber stopper of both the peptide vial and bacteriostatic water vial with alcohol.
Draw Water
Draw 2 mL of bacteriostatic water into a syringe.
Add Water to Vial
Insert the needle into the peptide vial and direct the water stream against the glass wall — not directly onto the powder.
Mix Gently
Swirl the vial gently until the powder is fully dissolved. Never shake. The solution should be clear and colorless.
Store Properly
Refrigerate at Refrigerated (2-8°C / 36-46°F). Approved pen devices can be stored at room temperature ≤30°C for up to 56 days.. Pen devices: 56 days after first use at room temp. Vials: per manufacturer guidelines..
Storage Temperature
Refrigerated (2-8°C / 36-46°F). Approved pen devices can be stored at room temperature ≤30°C for up to 56 days.
Shelf Life
Pen devices: 56 days after first use at room temp. Vials: per manufacturer guidelines.
Important Notes
- •Branded semaglutide (Ozempic/Wegovy) comes in pre-filled pen devices — no reconstitution needed.
- •Compounded semaglutide may require reconstitution; follow pharmacy instructions.
- •Pre-filled pens should be refrigerated before first use.
- •Do not freeze semaglutide, it degrades the protein structure.
- •Protect from direct sunlight.
- •Always follow the specific instructions provided with your prescription product.
Semaglutide Dosing Calculator
Calculate daily intake, cycle totals, and vials needed with pre-filled protocols →
Semaglutide Reconstitution Calculator
Calculate concentration, syringe units, and doses per vial with auto-filled values →
Safety & Side Effects
Reported Side Effects
- !Nausea (most common — reported in 20-44% of patients, typically improves with dose escalation)
- !Vomiting (reported in 15-25% during dose escalation, usually transient)
- !Diarrhea (reported in 15-30%)
- !Constipation (reported in 10-24%)
- !Abdominal pain (reported in 5-20%)
- !Decreased appetite (therapeutic effect, but can be excessive in some individuals)
- !Injection site reactions, mild redness, itching (infrequent with pen devices)
- !Headache, fatigue, dizziness (reported in 10-14%)
- !Gallbladder events including gallstones (increased risk, especially with rapid weight loss)
- !Pancreatitis (rare but reported; FDA boxed warning for GLP-1 class)
- !Thyroid C-cell tumors (observed in rodent studies — FDA boxed warning; clinical significance in humans uncertain)
Potential Interactions
- ⚡Slows gastric emptying; may affect absorption of oral medications. Time-sensitive medications should be monitored.
- ⚡Enhances insulin secretion, concomitant use with sulfonylureas or insulin increases hypoglycemia risk. Dose adjustment may be needed.
- ⚡May affect warfarin absorption — monitor INR when initiating or changing semaglutide dose.
- ⚡Oral contraceptives may have reduced absorption due to delayed gastric emptying, consider non-oral contraception.
- ⚡Interaction with other GLP-1 agonists or DPP-4 inhibitors; should not be combined due to overlapping mechanisms.
- ⚡Alcohol may worsen GI side effects and increase pancreatitis risk.
Important: Side effects and interactions listed here are compiled from published research and community reports. This is not a complete list. No formal drug interaction studies have been conducted for most research peptides. Always consult a qualified healthcare provider.
Research Studies
The following studies are referenced in this profile. PubMed IDs are provided where available for independent verification.
Once-weekly semaglutide in adults with overweight or obesity (STEP 1)
Landmark Phase III trial (N=1,961) showing 14.9% mean body weight reduction with semaglutide 2.4 mg vs 2.4% with placebo over 68 weeks. 32% of participants achieved ≥20% weight loss.
Two-year effects of semaglutide in adults with overweight or obesity (STEP 5)
Extended 104-week study showing sustained weight loss of 15.2% with continuous semaglutide treatment. Demonstrated that longer treatment duration maintained and slightly improved weight loss outcomes.
Semaglutide and cardiovascular outcomes in patients with type 2 diabetes (SUSTAIN-6)
Cardiovascular outcomes trial (N=3,297) showing 26% reduction in major adverse cardiovascular events with semaglutide versus placebo in type 2 diabetes patients at high cardiovascular risk.
Semaglutide and cardiovascular outcomes in obesity without diabetes (SELECT)
key trial (N=17,604) demonstrating a 20% reduction in major adverse cardiovascular events with semaglutide 2.4 mg in overweight/obese adults without diabetes. First GLP-1 RA to show CV benefit independent of diabetes.
Oral semaglutide versus subcutaneous semaglutide (PIONEER 4)
Head-to-head comparison showing oral semaglutide 14 mg produced comparable HbA1c reductions and weight loss to subcutaneous semaglutide 1.0 mg, establishing oral peptide delivery as a viable route.
Note: This is not an exhaustive list of all published research. Studies are selected for relevance and quality. Click PubMed IDs to verify sources independently. Inclusion does not imply endorsement of the peptide for any clinical use.
Frequently Asked Questions
Semaglutide is a GLP-1 receptor agonist — a peptide that mimics the incretin hormone GLP-1. It is FDA-approved for type 2 diabetes (Ozempic, Rybelsus) and chronic weight management (Wegovy). It works by reducing appetite, improving insulin secretion, and slowing gastric emptying.
Clinical trials show average weight loss of 14.9-17.4% of body weight over 68 weeks at the full 2.4 mg dose. Individual results vary; about 1/3 of participants lost over 20% of their body weight. Results depend on dose, lifestyle, and individual response.
Both contain semaglutide. Ozempic is approved for type 2 diabetes at doses up to 2.0 mg weekly. Wegovy is approved for weight management at a higher dose of 2.4 mg weekly, with a specific dose escalation schedule designed to minimize GI side effects.
Yes, clinical trials show that approximately 2/3 of lost weight is regained within one year of discontinuation. This is why semaglutide is approved as a chronic (ongoing) treatment rather than a short-term intervention. Lifestyle modifications can help mitigate regain.
Nausea (20-44%), vomiting, diarrhea, and constipation are most common, especially during dose escalation. These typically improve over time. The dose escalation protocol (gradually increasing dose over 16 weeks) is specifically designed to reduce GI side effects.
Compounded semaglutide is not FDA-approved and is produced by compounding pharmacies. While it contains the same active molecule, it lacks the manufacturing controls, purity verification, and clinical testing of branded products. The FDA has issued warnings about compounded GLP-1 products.
Yes — Rybelsus is an oral semaglutide tablet approved for type 2 diabetes. It uses a special absorption enhancer (SNAC) to facilitate gastric absorption. It must be taken on an empty stomach with minimal water. The oral form is not yet approved specifically for weight management.
Yes. The SELECT trial demonstrated a 20% reduction in major adverse cardiovascular events (heart attack, stroke, CV death) in overweight/obese adults, independent of diabetes status. The SUSTAIN-6 trial showed similar benefits in type 2 diabetes patients.
Research & Educational Use Only
All content is for informational and research purposes only. This site does not provide medical advice, diagnosis, or treatment. Consult a qualified healthcare professional before using any peptide or supplement.
The information presented here is compiled from published research studies and is intended for informational purposes only. Individual results may vary. Always consult with a licensed healthcare provider.