Semaglutide

What it is

A GLP-1 receptor agonist. Initial US approval was 2017, as Ozempic for type 2 diabetes; Wegovy followed in 2021 for weight management. It was the first of the modern weight-loss peptides and it remains the most prescribed, which is also why it has more label, more trial data and more post-market history behind it than anything else in this library.

How it works

It mimics GLP-1, a hormone your gut releases after eating, at 94% homology to the human peptide. GLP-1 receptors in the brain reduce appetite and increase fullness. Gastric emptying slows, so meals feel filling for longer. Insulin secretion rises and glucagon secretion falls, both only when glucose is elevated, which is why the same molecule treats diabetes without driving blood sugar to the floor.

Natural GLP-1 is destroyed within minutes by an enzyme called DPP-4. Semaglutide changes one amino acid at position 8 to resist it, and hangs a C18 fatty di-acid chain off position 26 so the molecule rides on albumin. That is what turns minutes into about a week.

One receptor. That is the whole mechanism, and it is why the numbers are smaller than tirzepatide's or retatrutide's, which add a second and a third.

What the trials showed

STEP 1, 1,961 people: 14.9% mean weight reduction at 68 weeks on 2.4 mg weekly, against 2.4% on placebo. Half lost 15% or more; on placebo, 4.9% did. The loss was gradual and flattened around 60 to 68 weeks.

SELECT is the one that matters most. 17,604 adults with established cardiovascular disease and without diabetes: major adverse cardiovascular events fell from 8.0% to 6.5%, a hazard ratio of 0.80. That is a health outcome rather than a weight outcome, and semaglutide is the only compound in this library approved on the strength of one. Tirzepatide has a cardiovascular outcome trial of its own in SURPASS-CVOT, but that was a non-inferiority comparison against another drug rather than against placebo, and it carries no cardiovascular indication.

Read the rest of SELECT before repeating the headline. Cardiovascular death on its own was 0.85 with a confidence interval crossing 1, so superiority was not established, and the label states plainly that an effect on heart failure has not been established. "Twenty percent fewer heart attacks and strokes" is true. "It prevents cardiovascular death" is not something this trial showed.

Dosing, and the thing people get wrong about it

Injection escalates over 16 weeks in four steps, reaching maintenance at week 17. The commonly repeated "16 to 20 weeks" is not the label's schedule.

Since June 2026 there is also a Wegovy tablet. Oral semaglutide itself is not new, Rybelsus has been sold since 2019, but the 25 mg strength is. Its four strengths are a titration schedule, not a menu: 1.5 mg for a month, then 4, then 9, then 25 mg as maintenance. Tablets must be taken in the morning, fasted, with no more than four ounces of plain water, swallowed whole, with nothing else to eat, drink or swallow for the next 30 minutes. Those numbers are specific because the pharmacology is: absorption was measurably better with 50 mL of water than 240 mL, and better with a longer fast.

Switching between the two is asymmetric, which falls straight out of the one-week half-life. Coming off the injection, wait a week before the first tablet. Coming off tablets, start the injection the next day.

This is a prescription medication. Claritide tracks what you were prescribed and will never suggest a dose or a change to one.

Three oral products, three ladders, one word on the bottle

This is the part worth slowing down for, because it is new and it is a genuine hazard.

There are now three different oral semaglutide products in the US, with three different strength ladders: Rybelsus at 3, 7 and 14 mg, Ozempic tablets at 1.5, 4 and 9 mg, and Wegovy tablets at 1.5, 4, 9 and 25 mg. The label states that Rybelsus and Ozempic tablets are not substitutable milligram for milligram.

A bottle labelled "4 mg semaglutide" does not tell you which product it is, and the products are not interchangeable at that number. If you log oral semaglutide, log the brand, not just the milligrams.

This gets more confusing before it gets less. All three Rybelsus strengths were listed as to-be-discontinued on 4 June 2026, being replaced by Ozempic tablets. During the changeover both will be in circulation, in the same medicine cabinets, on ladders that do not line up.

What it costs

List price is about \$1,349 a month, and almost nobody pays it. The manufacturer's own self-pay pharmacy prices the injection at \$349 a month and \$399 for the 7.2 mg dose. Novo Nordisk announced in February 2026 that the list price drops to \$675 from 1 January 2027, and stated that the change does not affect those self-pay prices.

Be careful with the \$149 tablet price you will see quoted. It applies to the 1.5 mg and 4 mg strengths, which are the first two rungs of the titration and not where you stay, and the 4 mg offer ends on 31 August 2026. Price the dose you expect to be on in six months, not the one you start on.

The cautions our sources raise

The GLP-1 class carries a boxed warning for medullary thyroid carcinoma based on rodent studies, making personal or family MTC history and MEN2 hard contraindications. Gallbladder events are associated with rapid weight loss from any cause. Lean mass is lost alongside fat in all large weight-loss interventions. Resistance training and adequate protein are the standard countermeasures.

On oral medications, the claim you will read everywhere is that slowed gastric emptying alters the absorption of everything you swallow. The Wegovy label says the opposite for the injection: in clinical pharmacology trials at 1 mg weekly, semaglutide did not affect the absorption of orally administered medications. The reviewed literature finds a lower peak and a later time to peak, consistent with slower emptying, and concludes that dose adjustments are probably not required. The +33% levothyroxine exposure figure that circulates as a thyroid rule belongs to the oral tablet, not the injection. What is sensible is closer monitoring for drugs with a narrow therapeutic index, not a blanket rule.

The label names the drugs it checked and found no clinically significant interaction with: lisinopril, warfarin in both forms, metformin, digoxin, ethinyl estradiol, levonorgestrel, furosemide, rosuvastatin and omeprazole. Two of those are worth calling out because the internet says otherwise. Warfarin is unaffected by semaglutide; the warfarin caution belongs to tirzepatide. So does the oral contraceptive warning with its four-week backup-method rule. Semaglutide's own label lists both contraceptive components as unaffected.