P Palthera
Hormone Analogues

Semaglutide

NN9535 / Ozempic / Wegovy / Rybelsus

Semaglutide is an acylated GLP-1 with a long-chain fatty diacid side chain that extends its via tight albumin binding, enabling once-weekly dosing. It is FDA-approved as Ozempic and Rybelsus (oral) for type 2 diabetes mellitus and as Wegovy for chronic weight management. The STEP programme provides the primary weight-management evidence and the SUSTAIN and SELECT programmes cover diabetes and cardiovascular outcomes.

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Hormone Analogues
Classification
GLP-1 receptor agonist · FDA-approved (Ozempic / Wegovy / Rybelsus)
Research stage
Phase III clinical evidence; FDA-approved for type 2 diabetes (Ozempic / Rybelsus) and chronic weight management (Wegovy)
Sequence
Acylated 31-residue GLP-1(7-37) analogue with C18 fatty diacid via γGlu-2xOEG linker at Lys26
Molecular weight
4113.6 Da

Snapshot

Key takeaways

A three-bullet snapshot before reading the full dossier.

  1. 01

    Long-acting GLP-1 with once-weekly subcutaneous dosing and an oral (Rybelsus) formulation.

  2. 02

    FDA-approved across three brand names for two indication families: type 2 diabetes and chronic weight management.

  3. 03

    STEP Phase III trial programme provides the primary obesity-indication evidence.

Dossier overview

4

research areas

3

references

3

handling notes

01

Mechanism of action

Semaglutide activates the GLP-1 , augmenting glucose-dependent insulin secretion, suppressing inappropriate glucagon release, delaying gastric emptying, and reducing appetite signalling via central GLP-1 receptor expression. The C18 fatty diacid side chain provides high albumin affinity and prolonged plasma .

02

Research applications

  • Type 2 diabetes glycaemic-control clinical research
  • Obesity and weight-management clinical research
  • Cardiovascular outcome research (SELECT trial)
  • GLP-1 pharmacology and incretin physiology

Evidence at a glance

What's behind this profile

3 citations · 2021–2022

Human
3

Studies in human volunteers or patients (incl. early-phase trials).

Publication years

  1. 21
  2. 22
20212022

Counts are derived from the cited studies below. A study covering both in vivo and in vitro work is counted by its primary model. Sample size is reported in 3 of 3 citations. Findings remain model-specific and are not extrapolated to therapeutic use.

03

Study references

Each profile cites a minimum of two peer-reviewed sources, with model type and reported sample size where the source provides it. Findings are model-specific and must not be extrapolated to therapeutic use.

Once-Weekly Semaglutide in Adults with Overweight or Obesity (STEP 1)

2021

Wilding JPH et al. · New England Journal of Medicine

Model
Phase 3 double-blind RCT in adults with overweight/obesity without type 2 diabetes
Sample
n=1961

Once-weekly semaglutide 2.4 mg was associated with mean body weight reduction of 14.9% versus 2.4% with placebo over 68 weeks.

PMID 33567185 DOI 10.1056/NEJMoa2032183

Effect of Subcutaneous Semaglutide vs Placebo as Adjunct to Intensive Behavioral Therapy on Body Weight (STEP 3)

2021

Wadden TA et al. · JAMA

Model
Phase 3a double-blind RCT in adults with overweight/obesity (without diabetes) plus intensive behavioural therapy
Sample
n=611

Semaglutide 2.4 mg with behavioural therapy was associated with mean body weight reduction of 16.0% versus 5.7% with placebo over 68 weeks.

PMID 33625476 DOI 10.1001/jama.2021.1831

Two-year effects of semaglutide in adults with overweight or obesity (STEP 5)

2022

Garvey WT et al. · Nature Medicine

Model
Phase 3 double-blind RCT in adults with overweight/obesity without type 2 diabetes
Sample
n=304

Semaglutide 2.4 mg was associated with sustained mean body weight reduction of 15.2% versus 2.6% with placebo over 104 weeks.

PMID 36216945 DOI 10.1038/s41591-022-02026-4

Evidence caveats

  • FDA approval covers specific indications. Clinical use is a medical decision and is not endorsed here.
  • Long-term safety surveillance is ongoing across multiple post-marketing studies. This profile summarises the primary STEP-programme registrational evidence.

04

Storage and handling

Approved product follows manufacturer cold-chain instructions. Research-grade material must be stored under controlled laboratory conditions per protocol.

  • Approved product follows the manufacturer label and pharmacy cold-chain.
  • Research-grade material requires controlled laboratory storage and full batch documentation.
  • Clinical decisions involving semaglutide require a qualified healthcare professional.

Common questions

Semaglutide FAQ

Plain-English answers backed by the citations on this profile — what it is, what's been studied, regulatory status, evidence limits.

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