Semaglutide Dosing Guide & Protocols (2026)

Semaglutide is a GLP-1 receptor agonist originally developed for type 2 diabetes that has shown remarkable efficacy for weight loss. It mimics incretin hormones that regulate blood sugar and appetite, leading to significant weight reduction in clinical trials.

FDA-approved as FDA-approved for weight loss and diabetes with extensive clinical trial data supporting its efficacy and safety profile.

Quick Reference: Community Dosing

Research peptide protocols use much lower doses than pharmaceutical formulations:

Start at 125 mcg weekly for 2-4 weeks to assess tolerance, then increase to 250 mcg weekly. Titrate slowly to minimize GI side effects.

For the full semaglutide peptide profile, vendor pricing, and stack protocols, see our Semaglutide peptide page.

Loading vs Maintenance

Loading (Weeks 1-4): Start at 125 mcg weekly to assess tolerance and minimize nausea. This allows your GI system to adapt to GLP-1 receptor activation.

Maintenance (Weeks 5-8): Increase to 250 mcg weekly if well-tolerated. Some protocols go to 500 mcg weekly, but most find 250 mcg effective for appetite suppression and weight loss.

The slow titration mimics FDA-approved protocols that emphasize gradual dose increases to maintain tolerability while achieving therapeutic effects.

Typical Protocol Lengths

• Weight loss cycles: 8-12 weeks on, 8 weeks off
• Metabolic support: 8 weeks on, 8 weeks off (ongoing cycles)
• Appetite control: 6-8 weeks as needed

Routes of Administration

Subcutaneous Injection (Standard Route)

Semaglutide is designed for subcutaneous injection and should not be taken orally (unlike BPC-157).

• Injection sites — Rotate between abdomen, thigh, and upper arm. Abdomen tends to have most consistent absorption.
• Injection volume — Typically 0.1 mL with an insulin syringe (29-31 gauge).
• Timing — Once weekly, same day each week. Morning on empty stomach is most common.

Important Notes

• Do not inject intramuscularly — absorption will be too rapid
• Rotate injection sites to prevent lipodystrophy
• Room temperature injection reduces injection site discomfort

Where These Numbers Come From: Clinical Context

Community research peptide doses are dramatically lower than FDA-approved pharmaceutical doses, and there's good reason for this difference:

FDA-Approved Doses

Weight loss indication:

• Titration: 0.25mg → 0.5mg → 1mg → 1.7mg → 2.4mg weekly
• Maintenance: 2.4mg weekly

Diabetes indication:

• Starting: 0.25mg weekly for 4 weeks
• Maintenance: 0.5-1mg weekly

Community Research Peptide Doses

Typical protocol: 250 mcg (0.25mg) weekly — 10x lower than FDA maintenance dose.

Why the Massive Difference?

Pharmaceutical vs. Research Grade: FDA-approved semaglutide (Novo Nordisk) undergoes rigorous quality control with guaranteed potency and purity. Research peptides have variable potency — some may be underdosed, others overdosed.

Conservative Approach: The community starts with doses equivalent to the lowest FDA titration steps and increases cautiously. This accounts for peptide variability and reduces side effect risk.

Individual Response: Some people are highly sensitive to GLP-1 agonists. Starting low allows assessment of individual tolerance before committing to higher doses.

Clinical Trial Context: The STEP trials that established semaglutide's efficacy used the full 2.4mg dose (Wilding et al., 2021, PMID 33567185), but community protocols prioritize tolerance over maximum efficacy.

Mechanism of Action

Semaglutide works through multiple pathways in the GLP-1 system:

Glucose-dependent insulin secretion — Stimulates insulin release only when blood glucose is elevated, reducing hypoglycemia risk compared to traditional diabetes drugs (Davies et al., 2021).

Glucagon suppression — Reduces glucagon secretion from pancreatic alpha cells during hyperglycemia, preventing excessive glucose production by the liver.

Gastric emptying delay — Slows stomach emptying, creating satiety and reducing post-meal glucose spikes. This is the primary mechanism behind appetite suppression (Nauck et al., 2021).

Central appetite regulation — Acts on GLP-1 receptors in the hypothalamus to reduce food intake and cravings. Brain imaging shows reduced activation in reward centers when viewing food (van Bloemendaal et al., 2014).

Cardiovascular protection — Reduces cardiovascular events in high-risk patients through mechanisms beyond glucose control, including endothelial function improvement (Marso et al., 2016).

Side Effects & Safety

Common Side Effects (>20% in trials)

GI effects (most common):

• Nausea (44% in STEP trials)
• Vomiting (24%)
• Diarrhea (30%)
• Constipation (24%)
• Stomach pain (20%)

Most GI side effects improve within 4-8 weeks and are dose-dependent — slower titration reduces incidence.

Serious Side Effects (Rare)

Pancreatitis — Risk appears low in clinical trials but exists. Stop immediately if severe abdominal pain develops.

Gallbladder problems — Rapid weight loss can increase gallstone formation risk.

Thyroid C-cell tumors — Black box warning based on animal studies. Avoid if personal/family history of medullary thyroid carcinoma or MEN 2 syndrome.

Hypoglycemia — Low risk with semaglutide alone, higher when combined with insulin or sulfonylureas.

Community-Reported Effects

• Fatigue during first few weeks
• Reduced alcohol tolerance
• Food aversions (can be beneficial for weight loss)
• Injection site reactions (mild)

Stacking Semaglutide

Semaglutide combines well with non-GLP-1 peptides for enhanced body composition effects.

Semaglutide + AOD-9604

AOD-9604 targets fat metabolism directly while semaglutide handles appetite and glucose. Complementary mechanisms for comprehensive weight loss.

Semaglutide + BPC-157

For people using semaglutide during cutting phases who need tissue recovery support.

What NOT to Stack

Avoid combining with other GLP-1 agonists (tirzepatide, liraglutide) — overlapping mechanisms increase side effect risk without proportional benefits.

Caution with insulin or diabetes medications — can increase hypoglycemia risk.

Frequently Asked Questions

What is the standard semaglutide dose?

Research peptide community protocols typically use 250 mcg once weekly, starting lower and titrating slowly. This is much lower than FDA-approved the FDA-approved weight loss dose (2.4mg/week) due to variability in research peptide purity and potency.

How do I titrate semaglutide?

Start at 125 mcg weekly for 2-4 weeks, then increase to 250 mcg weekly if well-tolerated. The slow titration minimizes GI side effects that cause many people to discontinue GLP-1 agonists.

How long should a semaglutide cycle last?

Most protocols run 8 weeks on, 8 weeks off cycles. Some extend to 12-16 weeks for significant weight loss goals, but cycling helps maintain receptor sensitivity and manage potential long-term effects.

What time of day should I inject semaglutide?

Most inject in the morning (AM) on an empty stomach for consistent absorption. The once-weekly dosing means exact timing isn't critical, but consistency helps maintain steady levels.

Is semaglutide FDA-approved?

Yes — as the FDA-approved weight loss dose (2.4mg/week) for chronic weight management and the FDA-approved diabetes dose (0.25-1mg/week) for type 2 diabetes. Research peptides are not FDA-approved and use different dosing protocols.

How do I reconstitute semaglutide?

Add 2 mL bacteriostatic water to a 5 mg vial (2,500 mcg/mL concentration). 250 mcg = 10 units on an insulin syringe. Swirl gently, refrigerate, use within 28 days.

Can semaglutide be stacked with other peptides?

Yes — commonly stacked with AOD-9604 for enhanced fat loss or healing peptides. Avoid stacking with other GLP-1 agonists due to overlapping mechanisms and increased side effect risk.

What are the main side effects of semaglutide?

GI side effects are most common: nausea (44%), vomiting (24%), diarrhea (30%), and constipation (24%). Most improve with time and slow titration. Rare serious effects include pancreatitis and gallbladder issues.

Related Guides

• Semaglutide Peptide Page — Vendor pricing, stack protocols, and full peptide profile
• Semaglutide vs Tirzepatide — GLP-1 vs dual agonist comparison
• Tirzepatide Dosing Guide — Dual agonist alternative to semaglutide
• Tesofensine Weight Loss Guide — Alternative weight loss compound

References

For educational and research purposes only. This is not medical advice. Research peptides are not FDA-approved for human use.