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Incretin-based agents · Endocrine

Semaglutide

Ozempic® · Rybelsus® · Wegovy®(brand names vary by market)

A weekly injection that changed what glucose lowering is expected to achieve.

Illustration of Semaglutide as a pen injectorSEM

Also: tablet

Mechanism

GLP-1 receptor agonist: glucose-dependent insulin release, suppressed glucagon, delayed gastric emptying, and central appetite suppression. The weight loss is a receptor effect, not a side effect.

Indications

  • Type 2 diabetes
  • Obesity and weight management
  • Cardiovascular risk reduction in established disease

Formulations

Pen injectorTablet

Dosing concepts

Escalation

Doses are escalated slowly over months. The escalation schedule exists to manage nausea, and rushing it is the commonest reason a patient abandons the drug.

Oral formulation

The oral form has strict administration requirements, taken fasting with a small sip of water and nothing else for 30 minutes, because absorption is otherwise negligible.

Before surgery

Delayed gastric emptying means a full stomach at induction; anaesthetic guidance now asks about it directly.

Concepts, not prescribing instructions. Practice numbers live in current references and local protocols.

Pharmacokinetics

Bioavailability
~89% subcutaneously; low and highly variable orally
Half-life
~1 week
Elimination
plasma: Proteolytic degradation; no dose adjustment for renal or hepatic impairment
Protein binding
>99% to albumin, which is what gives it the weekly half-life
Play with these concepts in the PK Lab

Adverse effects

  • Nausea, vomiting, diarrhoeacommonDose- and escalation-related; usually improves with time at a given dose.
  • Acute kidney injury via dehydrationseriousThe mechanism is vomiting rather than nephrotoxicity, which is why sick-day rules matter.
  • Pancreatitisserious
  • Gallbladder diseaseseriousRapid weight loss raises gallstone risk.
  • Diabetic retinopathy progressionseriousAssociated with rapid glucose lowering in patients with existing retinopathy.

Contraindications & precautions

Contraindications

  • Personal or family history of medullary thyroid carcinoma or MEN2
  • Type 1 diabetes as sole therapy
  • Pregnancy

Precautions

  • History of pancreatitis
  • Existing retinopathy
  • Gastroparesis
  • Planned surgery or endoscopy

Interactions

No curated interaction entries yet for this agent.

Monitoring

HbA1c and weight

Both are endpoints here

Gastrointestinal tolerance during escalation

It determines whether the drug survives

Renal function during any vomiting illness

Volume depletion is the realistic harm

Retinal review in patients with existing retinopathy

Rapid improvement in glucose can transiently worsen it

Counselling points

  • Same day each week; if you miss it, there is a window to take it late rather than doubling up.
  • Nausea is common at first and usually settles. Smaller meals, less fat, and stopping when full all help.
  • Tell us if you cannot keep fluids down, rather than pushing through.
  • Tell your surgeon or endoscopist that you take this: it slows stomach emptying.
  • Report severe abdominal pain radiating to the back.

Clinical pearls

  • The gastrointestinal effects are the mechanism working, not an intolerance. Reassurance plus a slower escalation rescues most patients who would otherwise stop.
  • It has cardiovascular and renal outcome benefit, which is what moved it, alongside the SGLT2 inhibitors, ahead of older agents in the treatment algorithms.
  • Different brands of the same molecule carry different indications and dose ranges; prescribing one for the other's indication is a real and frequent confusion.

References & review

  • Semaglutide product monograph (consult the current version for your market) (monograph)
  • Goodman & Gilman's The Pharmacological Basis of Therapeutics, 14th ed. (reference-work)

Last reviewed 2026-08-16 · jurisdiction: global · drug information changes; verify against current references before practice use.