Semaglutide
Ozempic, Wegovy, Rybelsus, Sema
The single-receptor GLP-1 agonist that started the category. Best-characterised long-term safety data of any compound on this site, including cardiovascular outcomes.
FDA-approved
FDA-approved as Ozempic (type 2 diabetes, 2017), Wegovy (chronic weight management, 2021, with a later cardiovascular risk-reduction indication) and Rybelsus (oral, diabetes).
What it is
Semaglutide is a GLP-1 receptor agonist - one receptor, not two or three. It is the least powerful of the three incretins documented here for weight loss, and simultaneously the one with the strongest evidence that taking it is good for you, which is a distinction worth holding onto.
What the evidence shows
STEP-1 produced roughly 14.9% mean weight reduction at 68 weeks on 2.4 mg weekly, versus about 2.4% on placebo.
More importantly, SELECT was a cardiovascular outcomes trial in over 17,000 people with obesity and existing cardiovascular disease but without diabetes. It found a significant reduction in major adverse cardiovascular events. No other compound on this site has anything comparable - this is hard-endpoint evidence that the drug prevents heart attacks and strokes, not merely that it moves a number on a scale.
That matters when comparing against retatrutide. Retatrutide has bigger weight-loss figures; semaglutide has proof that the intervention improves outcomes people actually care about.
Practical notes
- Slower titration than tirzepatide is usually needed for the same subjective tolerability, because there is no GIP arm blunting nausea.
- Constipation is the underrated one. Nausea fades; constipation frequently does not, and fibre plus hydration plus magnesium is the usual first-line response.
- Oral semaglutide is finicky. Absorption requires taking it fasted with no more than a small sip of water and waiting 30 minutes. Miss that and the dose is largely wasted.
The compounding situation
Semaglutide spent an extended period on the FDA shortage list, which permitted compounding pharmacies to produce it. Once a shortage is formally resolved, that permission narrows sharply. Compounded and grey-market "research" semaglutide sit in different legal categories with different risk profiles, and neither carries the identity guarantees of a pharmacy pen. Salt forms sold online - semaglutide sodium, semaglutide acetate - are marketing constructions used to argue a product is not the approved molecule; they are not established as equivalent, and there is no evidence base for them.
Side effects and warning signs
Commonly reported
- Nausea - the dominant complaint, worst in the days after a dose increase
- Constipation, often more persistent than the nausea
- Reflux, burping and early satiety
- Fatigue during aggressive deficits
- Muscle loss without deliberate protein and training
Stop and get medical help
- Severe abdominal pain radiating to the back - possible pancreatitis
- Right upper quadrant pain - gallstones are a recognised class effect
- Vision changes; a non-arteritic anterior ischaemic optic neuropathy signal has been examined in the class
- Personal or family history of medullary thyroid carcinoma or MEN2
Sources
From the community
Discussion for this compound concentrates in r/Semaglutide, r/GLP1 and r/Mounjaro.
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