Semaglutide

What it is

Semaglutide is a GLP-1 receptor agonist made by Novo Nordisk. It is the drug that put GLP-1s on the cultural map.

For weight loss, expected results sit at ~15% of starting body weight over 68 weeks at the top dose, which is less than tirzepatide but still substantially more than anything else previously available.

History

Approved for type 2 diabetes (Ozempic) in 2017, for obesity (Wegovy) in 2021, as an oral pill (Rybelsus) in 2019. The first of the modern wave.

How it works

Binds to the GLP-1 receptor — slows stomach emptying, increases insulin secretion when blood sugar is high, suppresses appetite.

Dosage

• Starting dose: 0.25 mg once weekly for 4 weeks.
• Titration: 0.5 mg → 1 mg → 1.7 mg → 2.4 mg, every 4 weeks.
• 2.4 mg is the Wegovy obesity dose. 1 mg is the standard Ozempic diabetes dose.
• Many people get strong appetite suppression at 0.5–1 mg and do not need to climb higher.

How it is taken

• Subcutaneous injection — abdomen, thigh, or upper arm.
• Same day each week. Rotate injection sites.

How to reconstitute

• A 5 mg vial with 2 ml of BAC water gives 2.5 mg/ml. A 0.25 mg starter dose is 10 units on a 1 ml insulin syringe.

How it should arrive

Sealed glass vial, white powder or puck. Intact cap. Cold shipping recommended but the lyophilised powder is reasonably stable at room temperature for shipping windows.

How it should look once reconstituted

Clear and colourless after gentle swirling.

What to expect, and when

• Appetite suppression: 1–3 days after first dose.
• 12 weeks: typically 4–7% body weight loss.
• 68 weeks at 2.4 mg: ~15% loss in trials.

Side effects

• Nausea, especially in the first week of each dose increase.
• Constipation, diarrhoea, indigestion, reflux.
• Sulphur burps.
• Fatigue early on.
• Hair shedding during rapid weight loss (mostly cosmetic, recovers).

Risks

• Pancreatitis.
• Gallstones.
• Thyroid C-cell tumours in rodents.
• Muscle loss without protein intake and resistance training.
• Aspiration risk during anaesthesia because of slowed stomach emptying — tell your anaesthetist.

Potential gains

• ~15% body weight loss over ~68 weeks at 2.4 mg.
• Improved blood glucose control.
• Reduced cardiovascular events (SELECT trial in non-diabetics).
• Reduced "food noise".

Other useful information

Semaglutide has the most accumulated long-term safety data of any GLP-1 class drug. If the strongest evidence base matters to you more than maximum weight loss, semaglutide over tirzepatide.