Weight Loss / Appetite Control Protocol

Primary Peptides

1. Semaglutide (Ozempic, Wegovy, Rybelsus)

FDA Approval Status:

• Ozempic (injectable): Type 2 diabetes (2017)
• Wegovy (injectable): Chronic weight management (2021)
• Rybelsus (oral): Type 2 diabetes (2019)

Mechanism: GLP-1 receptor agonist that:

• Slows gastric emptying (increases satiety)
• Reduces appetite via central nervous system effects
• Improves insulin secretion and reduces glucagon
• Reduces food cravings and hedonic eating

Dosing Protocol (Injectable - Weight Management):

• Month 1 (Weeks 1-4): 0.25mg once weekly
• Month 2 (Weeks 5-8): 0.5mg once weekly
• Month 3 (Weeks 9-12): 1.0mg once weekly
• Month 4 (Weeks 13-16): 1.7mg once weekly
• Month 5+ (Week 17+): 2.4mg once weekly (maintenance)

Administration:

• Route: Subcutaneous injection
• Sites: Abdomen, thigh, or upper arm
• Frequency: Once weekly, same day each week
• Timing: Any time of day, with or without food
• Device: Pre-filled pen (Ozempic/Wegovy pens)

Expected Results:

• Week 4-8: 2-3% body weight loss, appetite reduction begins
• Week 12-16: 5-8% body weight loss
• Week 28: 10-12% body weight loss
• Week 68: 15-17% body weight loss (average)
• Responders (>5% loss): 86% of participants
• Significant responders (>10% loss): 69% of participants

2. Tirzepatide (Mounjaro, Zepbound)

FDA Approval Status:

• Mounjaro (injectable): Type 2 diabetes (2022)
• Zepbound (injectable): Chronic weight management (2023)

Mechanism: Dual GIP/GLP-1 receptor agonist that:

• Activates both GIP and GLP-1 receptors (dual action)
• More potent appetite suppression than semaglutide
• Enhanced insulin sensitivity via GIP pathway
• Greater impact on energy expenditure

Dosing Protocol (Injectable - Weight Management):

• Weeks 1-4: 2.5mg once weekly
• Weeks 5-8: 5mg once weekly
• Weeks 9-12: 7.5mg once weekly
• Weeks 13-16: 10mg once weekly
• Week 17+ (optional): 12.5mg once weekly
• Week 21+ (optional): 15mg once weekly (maximum dose)

Administration:

• Route: Subcutaneous injection
• Sites: Abdomen or thigh
• Frequency: Once weekly, same day each week
• Timing: Any time of day, with or without food
• Device: Pre-filled pen (Mounjaro/Zepbound pens)

Expected Results:

• Week 12: 5-7% body weight loss
• Week 24: 10-13% body weight loss
• Week 40: 15-18% body weight loss
• Week 72: 20-21% body weight loss (average at 15mg)
• Responders (>5% loss): 91% of participants
• Significant responders (>10% loss): 83% of participants
• Exceptional responders (>20% loss): 50% of participants at 15mg

3. Liraglutide (Saxenda)

FDA Approval Status:

• Saxenda (injectable): Chronic weight management (2014)
• First GLP-1 agonist approved for weight loss

Dosing Protocol (Injectable - Weight Management):

• Week 1: 0.6mg once daily
• Week 2: 1.2mg once daily
• Week 3: 1.8mg once daily
• Week 4: 2.4mg once daily
• Week 5+: 3.0mg once daily (maintenance)

Administration:

• Route: Subcutaneous injection
• Frequency: Once DAILY (not weekly like semaglutide/tirzepatide)
• Timing: Any time of day, consistent timing preferred

Expected Results:

• Week 56: 8-9% body weight loss (average)
• Responders (>5% loss): 63% of participants
• Less effective than semaglutide or tirzepatide
• Daily injection less convenient than weekly

Protocol Comparison

Complete Protocol Timeline

Pre-Treatment (Weeks -2 to 0)

• Medical evaluation: Comprehensive health assessment
• Baseline measurements: Weight, BMI, waist circumference, blood pressure
• Laboratory tests: HbA1c, lipid panel, liver function, kidney function
• Contraindication screening: Personal/family history of MTC or MEN2
• Medication review: Adjust diabetes medications if needed
• Education: Injection technique, side effect management, dietary guidance

Initiation Phase (Weeks 1-4)

• Dose: Lowest starting dose (0.25mg semaglutide or 2.5mg tirzepatide)
• Purpose: GI adaptation, minimize side effects
• Expected: Mild appetite reduction, possible nausea (usually resolves)
• Weight loss: 1-3% (minimal, not therapeutic yet)
• Monitoring: Weekly check-ins for side effects

Escalation Phase (Weeks 5-16/20)

• Dose increases: Every 4 weeks as tolerated
• Purpose: Reach therapeutic dose while managing side effects
• Expected: Progressive appetite suppression, steady weight loss
• Weight loss: 0.5-1 kg per week average
• Monitoring: Bi-weekly to monthly check-ins
• Adjustments: May slow titration if side effects problematic

Maintenance Phase (Week 17/21+)

• Dose: Maximum tolerated dose (typically 2.4mg semaglutide or 10-15mg tirzepatide)
• Purpose: Sustained weight loss and maintenance
• Duration: Indefinite (weight regain occurs if stopped)
• Weight loss: Continues for 60-72 weeks, then plateaus
• Monitoring: Monthly to quarterly check-ins

Administration Guidelines

Injection Technique

1. Prepare injection site: Clean with alcohol swab, allow to dry
2. Select site: Abdomen (2 inches from navel), thigh, or upper arm
3. Rotate sites: Use different location each week
4. Inject: Insert needle at 90-degree angle, press button fully
5. Hold: Keep button pressed for 6 seconds after injection
6. Remove: Withdraw needle straight out
7. Dispose: Place used pen needle in sharps container

Storage

• Unopened pens: Refrigerate at 36-46°F (2-8°C)
• In-use pens: Can be kept at room temperature (up to 86°F/30°C) or refrigerated
• Duration: Use within 56 days of first use
• Protection: Keep away from light, do not freeze

Side Effects and Management

Common Side Effects (>10% incidence)

Gastrointestinal (Most Common):

• Nausea: 20-44% (dose-dependent, usually improves after 4-8 weeks)
• Management: Eat smaller meals, avoid fatty foods, ginger, slow titration

• Diarrhea: 9-30%
• Management: Stay hydrated, avoid trigger foods, consider anti-diarrheal if severe

• Vomiting: 5-24%
• Management: Eat slowly, avoid large meals, consider dose reduction if persistent

• Constipation: 11-24%
• Management: Increase fiber, hydration, physical activity

• Abdominal pain: 6-20%
• Management: Usually mild, resolves with time

Other Common Effects:

• Fatigue: 11-15% (may be related to caloric restriction)
• Headache: 8-14%
• Dizziness: 6-11%
• Injection site reactions: 5-10% (redness, itching, swelling)

Serious Side Effects (Rare but Important)

Pancreatitis (0.2-0.4%):

• Symptoms: Severe upper abdominal pain radiating to back, nausea, vomiting
• Action: Discontinue immediately, seek emergency care

Gallbladder Disease (1.6-2.8%):

• Risk: Rapid weight loss increases gallstone formation
• Symptoms: Right upper abdominal pain, nausea after fatty meals
• Action: Medical evaluation, may require cholecystectomy

Hypoglycemia (if on other diabetes drugs):

• Risk: Low when used alone, higher with insulin or sulfonylureas
• Prevention: Reduce doses of other diabetes medications
• Symptoms: Shakiness, sweating, confusion, rapid heartbeat

Thyroid C-Cell Tumors (Boxed Warning):

• Evidence: Seen in rodent studies, not confirmed in humans
• Contraindication: Personal or family history of MTC or MEN2
• Monitoring: Report neck lumps, hoarseness, difficulty swallowing

Contraindications and Precautions

Absolute Contraindications

• Personal or family history of medullary thyroid carcinoma (MTC)
• Multiple Endocrine Neoplasia syndrome type 2 (MEN2)
• Previous serious hypersensitivity to GLP-1 agonists
• Pregnancy (Category X - causes fetal harm)

Relative Contraindications / Use with Caution

• Pancreatitis history: Increased risk of recurrence
• Severe gastroparesis: May worsen gastric emptying delay
• Diabetic retinopathy: Rapid glucose lowering may worsen initially
• Renal impairment: Monitor for dehydration from GI side effects
• Gallbladder disease: Rapid weight loss increases gallstone risk
• Suicidal ideation history: Monitor mental health closely

Monitoring Requirements

Baseline (Before Starting)

• Weight, BMI, waist circumference
• Blood pressure, heart rate
• HbA1c (if diabetic)
• Lipid panel
• Comprehensive metabolic panel (kidney and liver function)
• Thyroid function (if indicated)

During Treatment

Weekly (First Month):

• Weight
• Side effect assessment
• Blood glucose (if diabetic)

Monthly (Months 2-6):

• Weight and BMI
• Blood pressure
• Side effect assessment
• HbA1c (if diabetic, every 3 months)

Quarterly (Maintenance):

• Weight and BMI
• Blood pressure
• HbA1c (if diabetic)
• Lipid panel
• Kidney and liver function

Expected Timeline and Results

Semaglutide 2.4mg (Wegovy)

• Week 4: 2-3% weight loss
• Week 12: 6-8% weight loss
• Week 28: 10-12% weight loss
• Week 52: 14-16% weight loss
• Week 68: 15-17% weight loss (plateau)

Tirzepatide 15mg (Zepbound)

• Week 4: 3-4% weight loss
• Week 12: 7-9% weight loss
• Week 24: 12-14% weight loss
• Week 40: 16-18% weight loss
• Week 72: 20-21% weight loss (plateau)

Cost Considerations

Brand Name Medications

• Wegovy (semaglutide): $1,349/month without insurance
• Zepbound (tirzepatide): $1,060/month without insurance
• Saxenda (liraglutide): $1,430/month without insurance

Insurance Coverage

• Coverage varies widely by plan
• Often requires prior authorization
• May require documented weight loss attempts
• Copays typically $25-$100/month if covered

Compounded Versions

• Cost: $200-$500/month
• FDA Warning: Quality concerns with compounded GLP-1s
• Risks: Incorrect dosing, impurities, unapproved salt forms
• Recommendation: Use FDA-approved products when possible

Discontinuation and Weight Regain

What Happens When You Stop

• Weight regain: Average 2/3 of lost weight regained within 1 year
• Appetite return: Hunger and cravings return to baseline
• Metabolic changes: Metabolic rate may decrease
• Timeline: Weight regain begins within weeks of stopping

Long-Term Use Considerations

• Most patients require indefinite treatment to maintain weight loss
• Long-term safety data (>2 years) is still accumulating
• Cost of lifelong treatment is significant consideration
• Lifestyle modifications essential for best outcomes

Regulatory and Safety Warnings

FDA Warnings

• Compounded GLP-1s: FDA warns about unapproved salt forms (e.g., semaglutide sodium, semaglutide acetate)
• Quality issues: Compounded products may contain impurities or incorrect doses
• Counterfeit products: Fake Ozempic pens have been identified
• Off-label use: Widespread use for cosmetic weight loss in non-obese individuals

Recommendations

• Use FDA-approved products from legitimate pharmacies
• Verify pen authenticity (check serial numbers, packaging)
• Avoid online sources of questionable legitimacy
• Work with qualified healthcare providers
• Report adverse events to FDA MedWatch

Conclusion

GLP-1 agonist peptides represent the most effective pharmacological treatment for weight loss currently available, with semaglutide and tirzepatide producing 15-21% body weight loss in clinical trials. These are FDA-approved medications with strong evidence supporting their efficacy and safety when used appropriately under medical supervision.

However, several important considerations apply:

• Require lifelong treatment to maintain weight loss
• Significant cost ($1,000-1,400/month)
• Common GI side effects (nausea, diarrhea, vomiting)
• Rare but serious risks (pancreatitis, gallbladder disease)
• Quality concerns with compounded versions

For individuals with obesity (BMI ≥30) or overweight with comorbidities (BMI ≥27), these medications can be life-changing when combined with lifestyle modifications. Medical supervision is essential for safe and effective use.