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Metabolic & GLP-1PeptideEvidence ACurated profile

Semaglutide

GLP-1 Receptor Agonist

aka GLP-1 analog

A long-acting GLP-1 receptor agonist. Extensively studied in clinical trials for glycemic control and body weight in T2D and obesity populations.

Molecular wt
4113.58g/mol
Formula
C187H291N45O59
CAS
910463-68-2
Half-life
7 days
established
Tmax
1.5 days
PubChem
56843331

Sequence

One-letter18 residues

H-Aib-EGTFTSDVSSYLEGQAAK(acyl)EFIAWLVRGRG

Read this before quoting the sequence
31-residue acylated GLP-1(7-37) analogue. Aib (alpha-aminoisobutyric acid) replaces Ala at position 8 of native GLP-1 (position 2 of the string), which stabilises the peptide against DPP-4; Lys26 carries a hydrophilic AEEA-AEEA-gamma-Glu spacer terminating in a C18 fatty di-acid that mediates albumin binding; Lys34 of native GLP-1 is replaced by Arg so that only one fatty di-acid attaches. Residue order taken from the PubChem systematic name of CID 56843331; the three modifications are stated in the Ozempic/Wegovy prescribing information.
Source ↗

Mechanism of action

Semaglutide is a glucagon-like peptide-1 (GLP-1) receptor agonist that mimics the action of the endogenous hormone GLP-1. It enhances insulin secretion in a glucose-dependent manner, suppresses glucagon release, and slows gastric emptying. These actions collectively help to regulate blood sugar levels and reduce appetite.

What the evidence actually shows

Grade A

Multiple large-scale human trials have demonstrated semaglutide's efficacy in improving glycaemic control and promoting weight loss. These studies consistently show significant reductions in HbA1c and body weight. However, long-term safety data beyond five years is still limited.

Regulatory status

Status
Approved prescription medicine (US and EU).
Approved as
OZEMPIC (subcutaneous, type 2 diabetes), WEGOVY (subcutaneous and oral tablets, chronic weight management) and RYBELSUS (oral semaglutide tablets); Novo Nordisk.
Clinical stage
Marketed / approved, with ongoing outcome trials.
UK
prescription_only

In the UK, semaglutide is approved as a prescription-only medication for the treatment of type 2 diabetes and obesity.

Source ↗

Pharmacokinetics

Half-life
7 days
Tmax
1.5 days
Absorption
subcutaneous
Elimination
both
Washout
35 days
Titration
0.25mg x4wk then 0.5mg x4wk then 1mg
Low-confidence pharmacokinetics
These figures are recorded as established rather than measured in a published PK study. Treat them as an order of magnitude. Anything downstream of them — accumulation, steady state, washout — inherits that uncertainty.

Dosing — what backs each figure

Semaglutide has three FDA-approved labels with fully specified regimens: WEGOVY (SC weekly, 0.25 mg escalating over 16 weeks to 1.7 or 2.4 mg maintenance, for obesity, CV risk reduction and MASH), OZEMPIC (SC weekly, 0.25 mg to a 2 mg maximum, for type 2 diabetes) and RYBELSUS (oral, 3 mg to 14 mg once daily with strict fasting administration rules). All are chronic therapies - the labels contain no cycling, washout or 'time off' concept.

ClinicalApproved labelling or a published human trial

  • 0.25 mg subcutaneously once weekly for weeks 1-4, 0.5 mg weeks 5-8, 1 mg weeks 9-12, 1.7 mg weeks 13-16, then maintenance from week 17: 2.4 mg (recommended) or 1.7 mg once weekly

    adults with obesity or overweight with a weight-related condition, and pediatric patients aged 12 years and older with obesity; same escalation applies for cardiovascular risk reduction · subcutaneous

    FDA label WEGOVY (semaglutide injection), NDA 215256 ↗

  • Same escalation to a maintenance dose of 2.4 mg subcutaneously once weekly

    adults with noncirrhotic MASH with moderate to advanced (F2-F3) liver fibrosis · subcutaneous

    FDA label WEGOVY, section 2 ↗

  • 0.25 mg subcutaneously once weekly for 4 weeks, then 0.5 mg weekly; may increase to 1 mg after at least 4 weeks, then to a maximum 2 mg weekly after at least a further 4 weeks (CKD patients: maintain at 1 mg)

    adults with type 2 diabetes mellitus; also for cardiovascular risk reduction and slowing CKD progression in type 2 diabetes · subcutaneous

    FDA label OZEMPIC (semaglutide injection), NDA 209637 ↗

  • 3 mg orally once daily for 30 days (not effective for glycemic control), then 7 mg once daily; may increase to 14 mg once daily after at least 30 days. Take on an empty stomach on waking with no more than 4 oz water, swallow whole, wait at least 30 minutes before food, drink or other oral medicines

    adults with type 2 diabetes mellitus, including cardiovascular risk reduction · oral

    FDA label RYBELSUS (semaglutide) tablets, NDA 213051 ↗

Handling and storage

Lyophilized
Refrigerated 24 months
Reconstituted
Refrigerated, use within 56 days (clinical labeling reference)

Do not freeze once reconstituted.

Source ↗
→ Reconstitution walkthrough→ Reconstitution calculator

Safety

Commonly reported
  • ·Nausea
  • ·Vomiting
  • ·Diarrhea
  • ·Constipation
Rarely reported
  • ·Pancreatitis
  • ·"Kidney injury"
  • ·"Thyroid tumors"
Contraindications
  • ·Personal/family history of medullary thyroid carcinoma or MEN 2
  • ·Pregnancy
  • ·Not for human therapeutic use in research-vial form — clinical products are the prescribed form
Drug interactions
  • ·May enhance the hypoglycemic effect of insulin and sulfonylureas

Nausea, vomiting, diarrhoea, constipation; rare pancreatitis, gallbladder events

Reported combinations

Reported as synergistic
  • ·Metformin
Reported as antagonistic
  • ·Dipeptidyl peptidase-4 (DPP-4) inhibitors

Combination claims in this dataset are largely unsourced and should be treated as folk knowledge until a citation appears beside them.

References (3)

Data provenance

Chemistry and citations on this page were checked against primary sources on 2026-08-14. Values that could not be verified were left blank rather than filled with a plausible guess.

Could not verify
regulatory.wada

Research use only
This profile is educational reference material. It is not medical advice, not a prescription, and not an endorsement of self-administration. Compounds discussed here are research chemicals and most are not approved for human therapeutic use.

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