Semaglutide Dosage Guide for Weight Loss

Semaglutide is a modified GLP-1 (glucagon-like peptide-1) analog with 94% structural homology to native human GLP-1. It was developed by Novo Nordisk and is FDA-approved under the brand names Ozempic® (for type 2 diabetes) and Wegovy® (for chronic weight management).

The STEP (Semaglutide Treatment Effect in People with Obesity) clinical trial program demonstrated mean weight loss of 14.9% of body weight at the 2.4 mg weekly dose over 68 weeks. Semaglutide works by activating GLP-1 receptors in the brain to reduce appetite, slow gastric emptying, and improve glycemic control.

The FDA-approved titration schedule for semaglutide (Wegovy®) follows a gradual dose escalation over 16 weeks to minimize gastrointestinal side effects:

Some research protocols use a lower maintenance dose of 1.0–1.7 mg weekly if gastrointestinal tolerance is a limiting factor. The 2.4 mg dose produced the greatest weight loss in clinical trials.

Semaglutide is administered once weekly via subcutaneous injection. The long half-life of approximately 7 days (168 hours) allows for convenient once-weekly dosing.

Timing: Inject on the same day each week. Semaglutide can be administered at any time of day, with or without meals. If a dose is missed by less than 5 days, administer as soon as possible. If more than 5 days have passed, skip the missed dose and resume on the regularly scheduled day.

Duration: Clinical trials demonstrated continued weight loss through 68 weeks of treatment. Weight regain is commonly observed upon discontinuation, so ongoing treatment may be necessary to maintain results.

Pre-filled pen formulations (Ozempic®, Wegovy®) do not require reconstitution. For compounded lyophilized semaglutide:

• Step 1: Clean vial stoppers with alcohol swabs.
• Step 2: Add the specified volume of BAC water to the vial. For a 5 mg vial, add 2 mL to yield 2.5 mg/mL.
• Step 3: Direct the stream against the glass wall. Allow to dissolve without shaking.
• Step 4: Gently swirl until the solution is clear and colorless.
• Step 5: Store refrigerated at 2–8°C. Use within 28 days.

Inject subcutaneously into the abdomen, thigh, or upper arm. Rotate injection sites weekly to prevent lipodystrophy.

Gastrointestinal side effects are dose-dependent and most common during titration:

• 0.25–0.5 mg: Mild nausea (20–30% of subjects), occasional constipation or diarrhea.
• 1.0–1.7 mg: Nausea intensity increases. Vomiting reported in approximately 5–10% of subjects. Reduced appetite becomes pronounced.
• 2.4 mg: In STEP 1, 44.2% of subjects reported nausea, 24.8% diarrhea, and 24.8% constipation. Most GI events were mild-to-moderate and transient.

Serious but rare side effects include pancreatitis, gallbladder disease, and potential thyroid C-cell tumors (observed in rodent studies at supratherapeutic doses).

Semaglutide carries a boxed warning regarding thyroid C-cell tumors observed in rodent studies. It is contraindicated in individuals with a personal or family history of medullary thyroid carcinoma (MTC) or Multiple Endocrine Neoplasia syndrome type 2 (MEN 2).

Do not use semaglutide concurrently with other GLP-1 receptor agonists. Monitor for signs of pancreatitis, gallbladder disease, and hypoglycemia (especially when combined with insulin or sulfonylureas). Always use under the supervision of a qualified healthcare provider.