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Semaglutide

From PeptidePlaza, the free peptide reference · Entry #001 · Metabolic · Hand-curated entry · Editorial standards

Research warning. Research chemicals are not for human consumption. Rodent studies have indicated a potential risk for thyroid C-cell tumors; contraindicated in individuals with a family history of Medullary Thyroid Carcinoma (MTC).

Semaglutide (also known as Ozempic, Wegovy, Rybelsus) is a metabolic research peptide. A long-acting GLP-1 analog distinguished by its C18 fatty diacid chain, enabling albumin binding and a half-life of ~7 days. One of the most clinically studied peptides in modern metabolic research.

Semaglutide is a glucagon-like peptide-1 (GLP-1) receptor agonist structurally homologous to human GLP-1 with approximately 94% sequence identity. Its C-18 fatty diacid side chain enables non-covalent binding to albumin, dramatically extending its half-life to ~7 days compared to native GLP-1 (~2 min). Research demonstrates potent insulinotropic effects, glucagon suppression, delayed gastric emptying, and significant reductions in body weight via hypothalamic appetite regulation.

1 Mechanism of action

Activates GLP-1 receptors in the pancreatic β-cells, hypothalamus, brainstem, and gut. Increases glucose-dependent insulin secretion, suppresses glucagon, slows gastric emptying, and reduces appetite via CNS pathways.

Primary targets: GLP-1R

2 Reported effects

Effects below are those reported in the published literature cited on this page. They are not claims of clinical benefit and not medical advice.

2.1 Reported benefits

  • Significant reduction in body weight in clinical models
  • Improved glycemic control via enhanced insulin secretion
  • Cardiovascular risk reduction in specific populations
  • Appetite suppression through hypothalamic regulation

2.2 Side effects

  • Gastrointestinal distress (nausea, vomiting, diarrhea)
  • Potential risk of thyroid C-cell tumors (based on rodent models)
  • Pancreatitis risk in predisposed individuals
  • Gallbladder disease (cholelithiasis)

3 Chemical and physical properties

CAS number910463-68-2
Molar mass4113.58 g/mol
Purity (typical)>99.5%
Half-life~7 days (SC injection)
Storage−20 °C, lyophilised powder, desiccated
SolubilitySterile water / bacteriostatic water
Receptors / targetsGLP-1R

3.1 Amino acid sequence

H-His-Aib-Glu-Gly-Thr-Phe-Thr-Ser-Asp-Val-Ser-Ser-Tyr-Leu-Glu-Gly-Gln-Ala-Ala-Lys(AEEAc-AEEAc-γGlu-C18 diacid)-Glu-Phe-Ile-Ala-Trp-Leu-Val-Arg-Gly-Arg-Gly-OH

4 Research dosages

0.25–2.4 mg SC once weekly (human RCT dosing); 2.4 mg is the approved obesity dose.

Dosages are reported from published protocols for reference only. Research chemicals are not for human consumption.

5 Research studies (9)

  1. Once-Weekly Semaglutide in Adults with Overweight or Obesity (STEP 1)
    New England Journal of Medicine (2021) · RCT · N=1,961
    Semaglutide 2.4 mg/week produced mean weight reduction of 14.9% vs 2.4% with placebo over 68 weeks.
    Key finding: 14.9% body weight reduction vs 2.4% placebo over 68 weeks — largest weight loss in a GLP-1 monotherapy RCT at the time.
  2. Semaglutide and Cardiovascular Outcomes in Obesity without Diabetes (SELECT)
    New England Journal of Medicine (2023) · RCT · N=17,604
    N=17,604. Semaglutide reduced major adverse cardiovascular events by 20% vs placebo in adults with overweight/obesity.
    Key finding: 20% reduction in MACE (major adverse cardiovascular events) — first GLP-1 to show CV benefit in non-diabetic population.
  3. GLP-1 Receptor Agonists: Mechanism and Clinical Evidence
    Journal of Clinical Investigation (2020) · Review · N/A (review)
    Comprehensive review of GLP-1 receptor agonist pharmacology, CNS mechanisms, and clinical applications.
    Key finding: GLP-1R agonism in hypothalamus and brainstem mediates appetite suppression independently of gastric effects.
  4. Analysis of the efficacy and safety of liraglutide, semaglutide, and tirzepatide for the treatment of overweight and obesity: a systematic review and network meta-analysis
    Journal of endocrinological investigation (2026) · Meta-Analysis
    GLP-1 and GLP-1/GIP receptor agonists produce clinically meaningful weight loss vs.
  5. Effectiveness & safety of semaglutide in weight reduction in obese nondiabetic patients: A systematic review and meta-analysis
    Medicine (2026) · Meta-Analysis · n=3613
    Further long-term randomized trials are needed to evaluate the durability of weight loss and the long-term safety profile of semaglutide.
  6. PYY(3-36) potentiates Semaglutide‑mediated mitochondrial modulation in MASLD
    American journal of physiology. Endocrinology and metabolism (2026) · RCT
    This study highlights the favourable effects of semaglutide and PYY3 36 mitigating mitochondrial dysfunction in MASLD, providing insight into their possible molecular mechanisms.
  7. Oral Semaglutide for Alcohol Use Disorder: A Randomized Clinical Trial
    The American journal of psychiatry (2026) · RCT
    These findings confirm previous results among non-treatment seekers with less severe AUD and suggest that continued development of semaglutide for AUD is warranted.
  8. Unconventional Applications of Semaglutide and Tirzepatide: From Oncology to Human Reproduction
    Biomedicines (2026) · RCT
    Across all domains, evidence derives predominantly from preclinical models, observational cohorts, and pharmacoepidemiologic studies, with randomized controlled trials remaining limited.
  9. Impact of semaglutide withdrawal on cardiometabolic profile and physiology of energy balance: Recovery effects after semaglutide termination - The REST trial study protocol
    PloS one (2026) · RCT
    This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

6 Safety and risk profile

6.1 Regulatory status

Semaglutide is currently classified as FDA approved. Approval applies to specific clinical indications and dosing; research-grade material is not the approved product.

Safety score: 85/100 — low concern. Derived from clinical data volume, known risks and regulatory status.

6.2 Contraindications

Conditions and populations in which use is contraindicated:

  • History of pancreatitis
  • Family or personal history of medullary thyroid carcinoma (MTC)
  • Pregnancy or lactation (insufficient safety data)
  • Severe gastrointestinal disease (gastroparesis)
  • Type 1 diabetes mellitus

6.3 Drug interactions

Drug or classInteractionRisk
Insulin / SulfonylureasIncreased hypoglycemia risk — dose adjustment of concomitant insulin secretagogues may be required.High
Warfarin & other oral anticoagulantsDelayed gastric emptying may alter absorption kinetics of orally administered drugs.Moderate
Oral contraceptivesTransient reduction in Cmax of ethinylestradiol/levonorgestrel with oral semaglutide.Low

6.4 Long-term risks

  • Thyroid C-cell hyperplasia/tumors (rodent data; human relevance uncertain)
  • Potential for pancreatitis with long-term use
  • Gallbladder-related adverse events
  • Unknown effects beyond 2–4 years of continuous use
  • Muscle loss during rapid weight reduction phase

6.5 Research best practices

  • Store lyophilized powder at −20 °C; reconstituted solution at 2–8 °C for up to 30 days
  • Titrate dose slowly to minimize GI side effects (4-week intervals between dose escalations)
  • Monitor pancreatic enzymes and gallbladder function in research protocols
  • Use bacteriostatic water for multi-dose vials to extend sterility
Safety data disclaimer. Safety assessments are based on published literature and are for educational reference only. Clinical evidence varies significantly between peptides. Always consult primary research and current regulatory guidance.

7 Frequently asked questions

How is Semaglutide used for weight loss?
In clinical and research settings, Semaglutide is used to drastically reduce appetite and caloric intake. It acts on the brain's hunger centers to increase feelings of fullness and slows digestion, leading to sustained weight reduction over time.
What kind of results are typical in research studies?
In large-scale clinical trials (like the STEP trials), participants using Semaglutide lost an average of 14.9% of their total body weight over 68 weeks, significantly outperforming diet and exercise alone.
How often does it need to be administered?
Due to its extended half-life, Semaglutide is typically administered as a once-weekly subcutaneous injection in research and clinical protocols.

8 References

  1. Effect of Oral Semaglutide on Cardiovascular Outcomes in Type 2 Diabetes by Extent of Vascular Disease PubMed (2026). Cavender MA, et al.. View source
  2. Effects of Oral Semaglutide on Dietary Intake and Body Composition in Japanese People With Type 2 Diabetes: A Prospective Observational Study in Clinical Practice PubMed (2026). Sawada M, et al.. View source
  3. Semaglutide-Induced Sarcopenia via GLP-1R-mTOR-Satellite Cells Axis and Muscle-Glucose Feedback Loop Potentially Leading to Refractory Hyperglycemia in Type 2 Diabetes: A Case-Driven Hypothesis PubMed (2026). Ahmed A, et al.. View source
  4. Development and validation of a sensitive HPLC-MS/MS method for the analysis of semaglutide in human plasma PubMed (2026). Tudan C, et al.. View source

Related compounds

Entries that share a target, a mechanism, or a research area with Semaglutide.

Liraglutideapproved

Also targets GLP-1R

The GLP-1 that proved the class. A C16 palmitoyl chain gave native GLP-1 a 13-hour half-life instead of two minutes — and produced the first cardiovascular outcome data for the family.

Tirzepatideapproved

Also targets GLP-1R

A 39-amino acid synthetic peptide that simultaneously activates GIP and GLP-1 receptors. Demonstrated greater weight loss than any approved single-agonist in clinical trials.

Survodutidemetabolic

Also targets GLP-1R

A 29-amino-acid dual agonist that pairs GLP-1 appetite suppression with glucagon-driven energy expenditure and hepatic fat oxidation. Its liver-fat data is the standout: up to 63% reduction.

Mazdutidemetabolic

Also targets GLP-1R

An oxyntomodulin-based dual agonist and the first GLP-1/glucagon co-agonist approved anywhere in the world — cleared in China for weight management in 2025.

Retatrutidemetabolic

Also targets GLP-1R

A novel triple receptor agonist targeting GLP-1, GIP, and glucagon receptors simultaneously — the first of its kind in human Phase 2 trials. Early data suggests it may surpass dual agonists.

CagriSemapeptide blends

Also targets GLP-1R

The first amylin + GLP-1 fixed-dose combination to reach phase 3. Two satiety systems in one weekly injection, and the closest any injectable has come to bariatric-surgery-range weight loss.

9 See also

For research reference only. Not medical advice. Peptides may be regulated or restricted in your jurisdiction. Entry validated by the PeptidePlaza Biomedical Research Desk; see editorial standards.

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