Semaglutide

Classification

GLP-1 receptor agonist (incretin mimetic)

Approval status

Approved medicine

Research status

Approved peptide medicine for defined diabetes and/or weight-management indications, depending on brand, dose and jurisdiction.

Molecular formula

C187H291N45O59

Molecular weight

4113.6 g·mol⁻¹ (free peptide; salt forms vary)

Sequence

Modified GLP-1(7–37) analogue with Aib substitution, C18 fatty-diacid acylation and spacer; full residue list is in approved product information.

Primary biological target

GLP-1 receptor (GCGR superfamily; class B GPCR)

Half-life

Approximately 7 days after subcutaneous administration (labelled once-weekly products)

Routes investigated

Subcutaneous, Oral (SNAC co-formulation, separate product)

Human evidence level

A — Approved clinical use / strong human evidence

A prescription peptide medicine used, in approved indications and formulations, for type 2 diabetes and chronic weight management. It is not a cosmetic ingredient and is not a general wellness supplement.

Synthetic long-acting analogue of human glucagon-like peptide-1, developed for once-weekly or oral incretin therapy.

Established (labelled / textbook receptor pharmacology)

Semaglutide binds and activates the GLP-1 receptor on pancreatic islet cells and in central and gastrointestinal circuits. Downstream Gs–cAMP signalling increases glucose-dependent insulin secretion and suppresses glucagon when glucose is elevated. Gastric emptying is slowed and appetite-related hypothalamic signalling is altered. These receptor-level effects are established for the GLP-1 agonist class and are described in regulatory product information. Central weight-loss circuitry details continue to be refined in physiology studies.

In people with an approved clinical indication, it can improve glycaemic control and support clinically supervised weight reduction. Effects are pharmacological, not nutritional.

• Type 2 diabetes

  A · Approved clinical use / strong human evidence

  Has been investigated, and in labelled products approved, for glycaemic control in type 2 diabetes.^{[2] [3]}

• Chronic weight management

  A · Approved clinical use / strong human evidence

  Once-weekly subcutaneous semaglutide 2.4 mg has been investigated in the STEP programme and is approved for chronic weight management in eligible adults in several jurisdictions.^[1]

• Cardiovascular outcomes

  A · Approved clinical use / strong human evidence

  Cardiovascular outcome trials have examined major adverse cardiovascular events in selected high-risk populations; labelled claims follow local product information.^[2]

Investigational findings are not proven clinical benefits unless an authority has labelled that indication.

Overall human evidence grade: A · Approved clinical use / strong human evidence

Animal, cell and in-vitro findings are listed separately from human effects.

• Mechanistic / translational pharmacology: Rodent and cellular GLP-1 receptor systems

  GLP-1 receptor agonism reproduces incretin effects on insulin, glucagon and energy intake in animal models. Human labelling rests on clinical trials, not on these models alone.

  Limitations: Animal energy-intake models do not establish human cosmetic or athletic indications.

  ^[1]

This section does not provide personalised medical dosing. Values are those reported in papers or protocols. Animal mg/kg doses are not converted to human doses.

Doses reported in human studies

1. STEP 1

   Dose: 2.4 mg

   Route: Subcutaneous

   Frequency: Once weekly

   Duration: 68 weeks

   Population: Adults with overweight or obesity

   Purpose: Weight-management efficacy and safety versus placebo

   ^[1]

2. SUSTAIN-6

   Dose: 0.5 or 1.0 mg

   Route: Subcutaneous

   Frequency: Once weekly

   Duration: Median 2.1 years

   Population: Type 2 diabetes, high CV risk

   Purpose: Cardiovascular outcomes

   ^[2]

Preclinical / animal study dosing

Insufficient reliable evidence identified.

Taken from regulator product information. This is not mixed with research-chemical schedules.

• FDA · United States

  Ozempic (semaglutide) injection

  Indication: Type 2 diabetes (see current USPI for full labelled uses)

  Regimen: Once-weekly subcutaneous injection after labelled escalation; maintenance doses are product-specific (commonly 0.5–2 mg range in USPI — verify current label).

  FDA Prescribing Information — Ozempic

• FDA · United States

  Wegovy (semaglutide) injection

  Indication: Chronic weight management in eligible patients

  Regimen: Once-weekly subcutaneous 2.4 mg after labelled escalation (verify current USPI).

  FDA Prescribing Information — Wegovy

• TGA · Australia

  ARTG-registered semaglutide presentations

  Indication: As per the current Australian Product Information for each registered brand

  Regimen: Follow the Australian PI. Compounded or research-chemical semaglutide is not an ARTG-registered equivalent.

  TGA Product Information / ARTG

Half-life

~1 week (subcutaneous once-weekly products)

Tmax

1–3 days to peak concentration after a subcutaneous dose (product-dependent)

Bioavailability

High after subcutaneous injection; oral tablets use an absorption enhancer (SNAC) with much lower absolute bioavailability

Metabolism

Peptide proteolysis; fatty-acid side chain prolongs albumin binding

Elimination

Metabolite clearance; see PI for renal comments

Numeric PK values should be taken from the current PI for the exact product.

Nausea, vomiting, diarrhoea, constipation, abdominal pain and reduced appetite are commonly reported in trials.

Serious events. Product information discusses pancreatitis, gallbladder disease, acute kidney injury secondary to dehydration, diabetic retinopathy complications in some diabetes trials, and a boxed warning in US labels regarding rodent thyroid C-cell tumours (human relevance uncertain).

Interactions. Hypoglycaemia risk increases with insulin or sulfonylureas. Delayed gastric emptying can affect oral drug absorption.

Populations often excluded from trials. Pivotal obesity trials excluded various endocrine and safety populations; see each protocol.

Pregnancy / lactation. Not recommended in pregnancy; see PI. Discontinue if pregnancy occurs, per label.

Organ impairment. Follow PI for renal and hepatic comments; GI adverse events can worsen dehydration.

Long-term safety. Outcome trials provide multi-year cardiovascular data in selected diabetes populations; lifelong safety in unselected wellness use is not established.

Unknowns. Safety of unregulated research-chemical injectables is not characterised and is not implied by approved-product data.

Contraindications. Product information typically contraindicates use in people with a personal or family history of medullary thyroid carcinoma or MEN2, and in hypersensitivity to the drug. Pregnancy, breastfeeding and specific GI diseases require specialist judgement. Always follow the Australian Product Information.

Australia — TGA

Registered prescription medicine in specific brands and indications on the ARTG. Not a listed complementary medicine. Not sold by Longevity Protocol.

United States — FDA

Approved (distinct NDAs/brands) for type 2 diabetes and for chronic weight management, among other labelled uses that must be read from the current USPI.

European Union — EMA

Centralised authorisations exist for diabetes and obesity products (brand-specific). Confirm SmPC for the exact product.

1. [1] Once-Weekly Semaglutide in Adults with Overweight or Obesity

   Wilding JPH et al. Once-Weekly Semaglutide in Adults with Overweight or Obesity N Engl J Med. 2021. doi:10.1056/NEJMoa2032183 PMID 33567185

   PMID 33567185DOI

2. [2] Semaglutide and Cardiovascular Outcomes in Patients with Type 2 Diabetes

   Marso SP et al. Semaglutide and Cardiovascular Outcomes in Patients with Type 2 Diabetes N Engl J Med. 2016. doi:10.1056/NEJMoa1607141 PMID 27633186

   PMID 27633186DOI

3. [3] Ozempic (semaglutide) prescribing information

   Novo Nordisk / FDA Ozempic (semaglutide) prescribing information 2024

   Open source