Semaglutide

Semaglutide is the most established member of the GLP-1 class and, for many, the entry point into incretin research. Unlike Tirzepatide or Retatrutide it acts on just one receptor, the GLP-1 receptor. In return it is the longest- and most broadly studied molecule of the group.

It is injected once a week. The long half-life of about seven days makes that possible, the highest figure among the compounds listed here. Semaglutide ships as a freeze-dried powder you dissolve in bacteriostatic water before the first use.

Semaglutide mimics the body's own GLP-1 hormone. It boosts the glucose-dependent insulin response, slows gastric emptying and engages the satiety centres in the brain. Day to day, most people mainly notice that appetite drops and the constant circling around food, the food noise, gets much quieter.

Because only one receptor is engaged, the per-milligram effect is milder than with the dual and triple agonists. In return the profile is very well understood and easy to steer.

Before you start, have everything ready. The list is short:

• The Semaglutide vial with the freeze-dried powder
• Bacteriostatic water to dissolve it
• U-100 insulin syringes for the injection (they also work for drawing the water, you just draw more often; a larger syringe is faster but not a must)
• Alcohol swabs for the vial cap and the skin
• A sealable sharps container for used needles

With everything clean and in one place, the rest is straightforward.

The powder is dissolved in bacteriostatic water. How much water you add sets the concentration, and with it how many units you later draw on the insulin syringe for your dose.

Use the calculator above for exactly this: pick your vial size and the water volume, and you instantly see the concentration and the units per dose. Roughly: less water means higher concentration and fewer units. For large vials from 20mg up, more water is worth it, otherwise the dose gets tiny and hard to read.

When dissolving, just add the bac water and let the powder dissolve. It does not matter if the water hits the powder directly, and swirling or shaking are both fine.

The injection is subcutaneous, into the fat layer under the skin. Common spots are the abdomen (keep about two finger-widths clear of the navel), the front of the thigh, or the back of the upper arm.

The short version:

• Clean the spot with an alcohol swab and let it dry
• Pinch up a small fold of skin
• Insert the needle at a 45 to 90 degree angle
• Inject slowly, wait a moment, then withdraw
• Put the needle straight into the sharps container

Rotate the site each time so the tissue does not get irritated. Never the same spot twice in a row.

Semaglutide has the largest data base of the whole class. In obesity research (the STEP programme), weekly dosing over a good year led to roughly 15 percent weight reduction on average. In diabetes and cardiovascular studies (SUSTAIN, SELECT), alongside the blood-sugar and weight effect, benefits on cardiovascular endpoints showed up too.

The individual studies with links are in the source block below.

The most common effects are gastrointestinal: nausea, fullness, sometimes diarrhoea or constipation. They show up mainly at the start and after each dose increase, and usually ease once the body has adjusted. That is exactly what the slow titration is for. Going up too fast is the most common avoidable mistake.

Semaglutide takes the hunger away, the rest is on you. A few things get more out of the research phase and keep you healthy:

• Enough protein. If you eat little, make the little you eat protein-rich, or you lose muscle along with fat.
• Drink enough. With low appetite you often drink less without noticing, and the risk of dehydration goes up.
• Resistance training. Keeps muscle mass while the weight comes off.
• Eat slowly. With delayed gastric emptying you fill up faster, big portions sit heavy.

Alcohol and very fatty meals make the nausea noticeably worse, especially early on.

The undissolved powder is robust, normal room temperature (around 20 to 25 degrees) is fine, ideally kept in the dark. Once dissolved, the solution goes into the fridge (2 to 8 degrees) and stays stable there for at least 8 to 10 weeks with barely any loss of potency, in practice considerably longer. The bacteriostatic water brings a preservative that keeps the dissolved form stable for longer.