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All peptides
GLP-1 receptor agonist

Semaglutide

Also known as: Ozempic, Wegovy, Rybelsus

Tier 1 — Human RCTReviewed 2026-04-30

The most-studied GLP-1 agonist in modern medicine, with Tier 1 evidence for diabetes, weight loss, and major adverse cardiovascular events.

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Overview

Semaglutide activates the GLP-1 receptor to slow gastric emptying, suppress appetite, and improve insulin secretion. It is FDA-approved as Ozempic (T2D, 2017), Wegovy (chronic weight management, 2021), and Rybelsus (oral T2D, 2019). The SUSTAIN, STEP, and SELECT trial programs together include tens of thousands of participants and remain the gold-standard human evidence for any peptide-based intervention discussed in this library.

Mechanism

GLP-1 receptor agonist with a fatty-acid linker that allows once-weekly subcutaneous (or daily oral) dosing. Effects include central appetite suppression via the hindbrain and hypothalamus, delayed gastric emptying, glucose-dependent insulin secretion, and glucagon suppression.

Evidence by indication

We classify each indication separately. The same peptide can be Tier 1 for one use and Tier 4 for another. Tiers reflect the published literature, not the strength of community framing.

Type 2 diabetes

Tier 1high confidence

SUSTAIN 1–10 trials (n>10,000) demonstrated HbA1c reduction across multiple comparators. FDA-approved as Ozempic in 2017.

Marso SP et al. 2016Novo Nordisk et al. 2024

Weight management (obesity / overweight with comorbidity)

Tier 1high confidence

STEP 1 (n=1,961) showed 14.9% mean body weight reduction at 68 weeks vs 2.4% on placebo. FDA-approved as Wegovy in 2021.

Wilding JPH et al. 2021Novo Nordisk et al. 2024

Major adverse cardiovascular events (MACE) reduction

Tier 1high confidence

SELECT (n=17,604) demonstrated a 20% relative reduction in MACE in adults with overweight/obesity and established cardiovascular disease without diabetes. FDA approved this expanded indication in 2024.

Lincoff AM et al. 2023

Diabetic retinopathy

Tier 2medium confidence

SUSTAIN-6 reported a higher numerical rate of retinopathy complications in the semaglutide arm; signal is debated and likely linked to rapid HbA1c reduction. Worth flagging for users with established retinopathy.

Marso SP et al. 2016

Studied dose ranges

The ranges below come from published trial protocols where available, and from documented self-experimenter consensus where the literature does not include human dose-finding work. The notes flag which is which.

250–2,400 mcgonce weekly · subcutaneous

Wegovy titration: 0.25 mg → 0.5 mg → 1.0 mg → 1.7 mg → 2.4 mg, escalating every 4 weeks. Ozempic for T2D ranges 0.25 mg → 2 mg.

3,000–14,000 mcgonce daily · oral (Rybelsus)

Oral semaglutide with SNAC absorption enhancer. 3 mg → 7 mg → 14 mg.

Contraindications

  • Personal or family history of medullary thyroid carcinoma (boxed warning)
  • Multiple Endocrine Neoplasia syndrome type 2 (boxed warning)
  • Hypersensitivity to semaglutide or excipients
  • Pregnancy: avoid; discontinue 2 months before planned conception
  • Caution: history of pancreatitis, severe gastroparesis, gallbladder disease

Reported side effects

  • Nausea (most common; usually titration-dependent)
  • Vomiting, diarrhea, constipation
  • Decreased appetite
  • Injection site reactions
  • Hypoglycemia (when combined with insulin or sulfonylureas)
  • Pancreatitis (rare)
  • Gallbladder disease with rapid weight loss
  • Possible exacerbation of diabetic retinopathy with rapid HbA1c drops

Reconstitution & storage

Pre-filled FlexTouch pens or pre-filled single-use Wegovy injectors. No reconstitution required for FDA-approved products. Compounded semaglutide sold by some clinics is not FDA-approved; quality and identity vary by source.

Storage. Refrigerate 2–8 °C before first use. Pen in use can be stored at room temperature ≤30 °C for up to 56 days. Do not freeze.

Open the peptide calculator → to compute exact draw volumes for your specific vial and BAC water choice.

Editorial note

The retinopathy signal is real but small; do not bury it. Compounded semaglutide is a regulatory and quality concern — flag it explicitly to users without moralizing.

Citations

  1. [1]
    Semaglutide and Cardiovascular Outcomes in Patients with Type 2 Diabetes (SUSTAIN-6)
    Marso SP, Bain SC, Consoli A, et al. · New England Journal of Medicine · 2016 · PMID 27633186
    Cardiovascular outcomes in T2D and the retinopathy signal.
    View source
  2. [2]
    Once-Weekly Semaglutide in Adults with Overweight or Obesity (STEP 1)
    Wilding JPH, Batterham RL, Calanna S, et al. · New England Journal of Medicine · 2021 · PMID 33567185
    Tier 1 evidence for weight loss in obesity; basis for Wegovy approval.
    View source
  3. [3]
    Semaglutide and Cardiovascular Outcomes in Obesity without Diabetes (SELECT)
    Lincoff AM, Brown-Frandsen K, Colhoun HM, et al. · New England Journal of Medicine · 2023 · PMID 37952131
    MACE reduction in overweight/obese patients without diabetes.
    View source
  4. [4]
    Ozempic (semaglutide) Prescribing Information
    Novo Nordisk · FDA-approved label · 2024
    Boxed warnings, dose ranges, contraindications for T2D.
    View source
  5. [5]
    Wegovy (semaglutide) Prescribing Information
    Novo Nordisk · FDA-approved label · 2024
    Dose ranges and contraindications for chronic weight management.
    View source