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Semaglutide

Metabolic

Also known as Ozempic, Wegovy, Rybelsus

GLP-1 receptor agonist. FDA approved.

How it works

94% homologous to human GLP-1, modified at position 26 with a C18 diacid so that it binds albumin and resists DPP-4. Slows gastric emptying, increases glucose-dependent insulin release and acts centrally to reduce appetite.

SubcutaneousOral

In the body

Half-life
6.7 days
Time to peak
3 d
90% gone after
22.3 d
Builds up to
1.94×
Steady state after about 33.9 d at once weekly.
Aug 3Aug 6Aug 9Aug 12Aug 15Aug 18Aug 2112:09 PM

Shape of a single dose, modelled as one compartment with first-order absorption. The peak is normalised to 100% because bioavailability and volume of distribution are not published for most of these compounds.

About one week. Measured at 145 to 165 hours for the 2.4 mg dose.

What happens, and when

  1. 0 min, 24 hAbsorbing slowly. Gastric emptying begins to slow.
  2. 24 h, 4 dPeak plasma levels, 1 to 3 days after the dose.
  3. 4 d, 7 dDescending. About 47% of peak remains at day 7.
  4. 7 d, 14 dBetween doses at steady state the swing is small, accumulation is roughly 1.9-fold.

Doses

250 mcg, 7.2 mgonce weeklyApproved label

Wegovy maintenance is 2.4 mg, extendable to 7.2 mg. Ozempic maintenance is 0.5, 1 or 2 mg.

Wegovy escalation to 2.4 mg

Wegovy prescribing information, Table 1 · 32 weeks total

  1. wk 1, 4250 mcg4 weeks
  2. wk 5, 8500 mcg4 weeks
  3. wk 9, 121 mg4 weeks
  4. wk 13, 161.7 mg4 weeks
  5. wk 17, 322.4 mgMaintenance from week 17.

If a step is not tolerated, the label suggests delaying escalation by 4 weeks rather than pushing on. Missing two consecutive doses means restarting escalation at a lower dose.

Ozempic escalation to 2 mg

Ozempic prescribing information, section 2 · 24 weeks total

  1. wk 1, 4250 mcgStarting dose, not for glycaemic control.
  2. wk 5, 8500 mcg4 weeks
  3. wk 9, 121 mg4 weeks
  4. wk 13, 242 mg12 weeks

Side effects

  • Nausea, vomiting, diarrhoea, constipation, abdominal pain
  • Gallbladder disease
  • Injection site reactions
  • Pancreatitis, uncommon
  • Diabetic retinopathy complications in people with existing retinopathy

Cautions

  • Boxed warning: thyroid C-cell tumours in rodents. Contraindicated with a personal or family history of medullary thyroid carcinoma or MEN 2.
  • Stop at least 2 months before a planned pregnancy, because of the long half-life.
  • Caution with insulin or sulfonylureas.

Status

FDA approved. Compounded semaglutide is outside that approval, and the FDA has warned specifically about salt forms (semaglutide sodium or acetate) that are not the approved active ingredient.

Sources

Reference information for personal record-keeping. Not medical advice, and not a recommendation to use any of these compounds.