Semaglutide

Areas of active research — not promised effects

Each tag links to other compounds with research into that goal. Research use only: these are areas of study, not human-use claims.

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Semaglutide is a fully FDA-approved prescription medication available as Ozempic (subcutaneous injection, type 2 diabetes and cardiovascular risk reduction; NDA 209637, approved December 2017), Rybelsus (oral tablets, type 2 diabetes; NDA 213051, approved September 2019), and Wegovy (subcutaneous injection, chronic weight management and cardiovascular risk reduction; NDA 215256, approved June 2021; Wegovy HD 7.2 mg approved 2026). It is not a controlled substance under the CSA. As a fully approved drug, semaglutide is not subject to the FDA Category 1/2 bulk-peptide compounding restrictions under docket FDA-2025-N-6895 that apply to unapproved research peptides (fda19=false). The semaglutide drug shortage was declared resolved by FDA in early 2025, ending the shortage-based exemption that had permitted large-scale industrial compounding at 503B outsourcing facilities; compounded semaglutide 503B compounding deadlines passed in early 2025. On April 30, 2026, FDA proposed excluding semaglutide (along with tirzepatide and liraglutide) from the 503B Bulk Drug Substances List, citing no clinical need for outsourcing-facility compounding of these drugs given adequate commercial supply (91 Fed. Reg. ~23431; public comment deadline June 29, 2026). 503A patient-specific pharmacy compounding of semaglutide is subject to the standard prohibition on essentially copying commercially available drugs except in limited, documented circumstances.

Confirmed high-severity market-integrity event (enforcement / recall / counterfeit)

Transparent blend · bci-1.0 · never paid-placement

Primary name

Semaglutide

Origin

Semaglutide is a synthetic analog of endogenous glucagon-like peptide-1 (GLP-1) developed by Novo Nordisk. It shares 94% amino acid sequence identity with native human GLP-1(7-37), with two modifications that distinguish it from the parent hormone: a substitution of alanine-8 with alpha-aminoisobutyric acid (Aib) to confer resistance to dipeptidyl peptidase-4 (DPP-4) cleavage, and attachment of an octadecandioic acid (C18 di-acid) fatty-acid chain to lysine-26 via a hydrophilic PEG-containing linker. The fatty-acid moiety enables high-affinity, reversible albumin binding that dramatically reduces renal clearance and proteolytic degradation, extending the plasma half-life to approximately 165 hours (about one week). This prolonged half-life supports once-weekly subcutaneous dosing for the injectable formulations (Ozempic approved 2017 for type 2 diabetes; Wegovy approved 2021 for chronic weight management). An oral formulation (Rybelsus) co-formulated with the absorption enhancer SNAC (sodium N-[8-(2-hydroxybenzoyl)aminocaprylate]) was approved in 2019 for type 2 diabetes, representing the first approved oral GLP-1 receptor agonist.

Registry IDs

PubChem CID

56843331

CAS

910463-68-2

InChIKey

DLSWIYLPEUIQAV-CCUURXOWSA-N

Molecular formula

C187H291N45O59

Molar mass

4114 g/mol

Monoisotopic

4111.1153770 Da

InChIKey

DLSWIYLPEUIQAV-CCUURXOWSA-N

Appearance

Clear, colorless to slightly yellow solution in prefilled multi-dose pen injector (commercial subcutaneous presentations); oral tablet (Rybelsus) is white to light yellow. Research or compounded forms may be lyophilized white to off-white powder.

Solubility

Soluble in aqueous buffers at physiological pH; the C18 di-acid fatty-acid chain…

Sequence not available in current seed.

Stability: The C18 fatty-acid PEG linker modification and Aib-8 substitution confer dual resistance: albumin binding shields against DPP-4 proteolysis, and Aib prevents en

Vial sizes

null mg · null mg · null mg

Purity grades

pharmaceutical grade

Salt forms

Free base (primary)

• GHS hazard class on file
• PPE & spill response
• Disposal guidance
• Not-for-human-consumption posture

How much research exists, and of what maturity — never a verdict on whether it works.

Mechanism of action

• Semaglutide binds selectively and with high affinity to the GLP-1 receptor, a Gs-protein-coupled receptor expressed most densely in pancreatic beta cells, the hypothalamus, brainstem, myocardium, and gastrointestinal tract
• Receptor activation elevates intracellular cyclic AMP via adenylyl cyclase, potentiating glucose-dependent insulin secretion from pancreatic beta cells while suppressing glucagon release from alpha cells — both effects diminish as blood glucose approaches euglycemia, substantially reducing hypoglycemia risk compared with sulfonylurea secretagogues
• In the central nervous system, semaglutide activates hypothalamic and brainstem GLP-1 receptors (including arcuate nucleus POMC/CART neurons and area postrema neurons) to reduce appetite, increase satiety signaling, and modulate reward-related feeding behavior, collectively producing dose-dependent reductions in caloric intake that underlie the weight-loss efficacy observed at the higher doses used in Wegovy
• Additionally, semaglutide slows gastric emptying, attenuating postprandial glucose excursions, and exerts direct cardioprotective effects through GLP-1 receptor signaling in cardiomyocytes and vascular endothelium, which are thought to contribute to the demonstrated reductions in major adverse cardiovascular events in the SUSTAIN-6 and SELECT outcome trials

Pharmacokinetics (ADME)

Half-life

~165 hours (~7 days) after subcutaneous injection; supports once-weekly dosing

Clearance

Apparent clearance approximately 0.05 L/h following subcutaneous administration; primarily metabolized via endopeptidase cleavage and beta-oxidation of the fatty-acid chain; excretion is predominantly renal (~49%) and fecal (~24%) as metabolites; intact semaglutide is not detected in urine or feces. No clinically relevant organ-specific accumulation; minor dose adjustment guidance exists for severe renal impairment with oral formulation per approved labeling.

PK–PD note: Peak plasma concentration (Tmax) reached 1–3 days after subcutaneous injection. Absolute bioavailability ~89% via the subcutaneous route. Plasma protein binding >99% (predominantly albumin), accountin…

Reading the evidence

• Evidence quality and gaps vary by application — see the cited grades above.
• Indexed-article counts span all evidence tiers, not only completed human trials.
• No first-party human-dosing, efficacy, or benefit claims are made here.

Key reviews & evidence-gap sources

• Bracchiglione et al. 2025 — Cochrane systematic review, 'Semaglutide for adults living with obesity' (CD015092.pub2) — 18 RCTs, 27,949 participants; search to 17 Dec 2024; manufacturer involved in 17 of 18 included studies (most manufacturer-funded); clinically relevant weight loss vs placebo, adverse-event-driven discontinuation notable at long-term follow-up, effects on QoL/MACE/mortality minimal or uncertain.
• Marso et al. 2016 (NEJM) — SUSTAIN-6: Semaglutide and Cardiovascular Outcomes in Patients with Type 2 Diabetes — NCT01720446; completed, results published. Non-inferiority-designed CV-safety trial (n=3,297); MACE 6.6% vs 8.9%, HR 0.74 (95% CI 0.58–0.95), meeting a pre-specified superiority test (driven mainly by nonfatal stroke/MI, not CV death). Attributed trial finding, not a first-party claim.
• Wilding et al. 2021 (NEJM) — STEP 1: Once-Weekly Semaglutide in Adults with Overweight or Obesity — NCT03548935; completed, results published (n=1,961, no diabetes). Semaglutide-arm mean body-weight change −14.9% vs −2.4% placebo (between-group −12.4 pp); 86.4% reached ≥5% loss vs 31.5%. The 14.9% is the arm mean, not the delta.
• Lincoff et al. 2023 (NEJM) — SELECT: Semaglutide and Cardiovascular Outcomes in Obesity without Diabetes — NCT03574597; completed, results published; 17,604 adults with CVD + overweight/obesity, no diabetes. Primary MACE 6.5% vs 8.0%, HR 0.80 (95% CI 0.72–0.90; P<0.001) ≈ 20% relative risk reduction.
• Husain et al. 2019 (NEJM) — PIONEER 6: Oral Semaglutide and Cardiovascular Outcomes in Patients with Type 2 Diabetes — NCT02692716; completed, results published (n=3,183). MACE HR 0.79 (95% CI 0.57–1.11; P<0.001 for non-inferiority). CV-death (HR 0.49) and all-cause-death (HR 0.51) reductions were pre-specified SECONDARY endpoints, nominal/hypothesis-generating (not powered for superiority).
• Aroda et al. 2023 — pooled safety/tolerability across the SUSTAIN + PIONEER phase-IIIa programmes — Program-level roll-up corroborating the SUSTAIN and PIONEER completed-and-published trial counts.

5 registered trials — 0 currently recruiting.

Phase 1
NCT06149260
Subcutaneous Semaglutide in Systemic Scleroderma

UNKNOWN

Phase 1
NCT03357380
A Study on How Semaglutide Works on Early Stages of Scar Tissue in the Liver Assessed by Pictures of the Liver

COMPLETED

Phase 4
NCT06571383
STEP TEENS Weight Maintenance: A Research Study on How Well Semaglutide Helps Teenagers With Excess Body Weight to Lose Weight and Maintain Weight Loss

ACTIVE_NOT_RECRUITING

Phase 2
NCT07220629
Study to Explore the Safety and Efficacy of NT-0796 as an Adjunct to Semaglutide in Participants With Obesity (RESOLVE-2)

ACTIVE_NOT_RECRUITING

Phase 3
NCT01720446
Trial to Evaluate Cardiovascular and Other Long-term Outcomes With Semaglutide in Subjects With Type 2 Diabetes

COMPLETED

Summary (literature)

The predominant adverse effects of semaglutide are gastrointestinal — nausea (up to ~44% of participants in STEP trials), vomiting, diarrhea, constipation, and abdominal discomfort — which are typically mild to moderate in severity, concentrated during dose escalation, and dimini…

WADA status

As of the 2026 WADA Prohibited List (effective January 1, 2026), semaglutide is NOT classified as a prohibited substance in sport. Semaglutide and tirzepatide a…

Dominant research route: Subcutaneous injection (once weekly) is the dominant human research and approved-label route (Ozempic, Wegovy) — used in essentially all pivotal RCTs. Oral tablet dosing (Rybelsus, once daily) is separately FDA-approved but is a distinct SNAC-enhanced delivery technology with far lower systemic exposure. Preclinical mechanistic/metabolic rodent work commonly uses intraperitoneal (IP) dosing; intravenous (IV) is used in early-phase human and animal PK purely as the reference route for absolute-bioavailability calculation, not as a clinical route. No published human intramuscular, intranasal, or topical PK study was located this pass, so those routes are omitted rather than estimated.

The FDA-approved clinical route (Ozempic, Wegovy) — once-weekly SC dosing was the route used in the pivotal human RCT programs (SUSTAIN, STEP) and in a dedicated dose-ranging / absolute-bioavailability trial (NCT02231684). A published population-PK analysis pooled 353 subjects / 10,573 concentration values from SC (and IV) trials.

Bioavailability: Absolute bioavailability 89% (Ozempic FDA label, §12.3). Median time to maximum concentration 1–3 days post-dose; similar systemic exposure whether injected in the abdomen, thigh, or upper arm. Elimination half-life ~1 week (149–165 h), attributed to >99% plasma-albumin binding — what enables once-weekly dosing.

The dominant human research and approved-label route. Figures describe the FDA-approved product's studied pharmacokinetics — no human-dosing protocol is implied.

FDA-approved as RYBELSUS, a once-daily tablet co-formulated with the absorption enhancer SNAC; characterized in single/multiple-ascending-dose and dosing-condition (fasting time, water volume) trials in healthy subjects and in type 2 diabetes.

Bioavailability: Absolute bioavailability only 0.4–1% under recommended dosing conditions (FDA label, 3/7/14 mg); a manufacturer (Novo Nordisk) pooled clinical-pharmacology analysis (Overgaard et al. 2021) estimates ≈0.8% (95% CI 0.736–0.864%), rising to ≈1.4% with a 120-min post-dose fast. [Verification: the pooled analysis is a manufacturer analysis, NOT independent — all authors are Novo Nordisk employees. Note a separate higher-dose oral OZEMPIC tablet product now on the same label carries 1–2% BA, which does NOT apply to the Rybelsus 0.4–1% figure.] Absorption is local in the stomach, reduced by food and larger water volumes; Tmax ≈1 h. Distribution/elimination then follow the SC model.

A structurally distinct oral-delivery technology (SNAC-mediated local gastric absorption enhancement) — not evidence that unformulated semaglutide is orally absorbed. See oralStabilityNote.

Used as a comparator/reference dose in early-phase human clinical-pharmacology trials to anchor the SC route's absolute-bioavailability estimate; formally characterized with quantified PK in Sprague-Dawley rats alongside SC dosing.

Bioavailability: 100% bioavailable by definition; the reference used to derive the SC route's 89% absolute bioavailability in humans. In rats (0.02 mg/kg IV vs 0.1–0.2 mg/kg SC; Lee et al. 2023, PMID 36989942), plasma half-life averaged 7.22–9.26 h and SC bioavailability was 76.65–82.85% — markedly shorter/lower than the ~1-week half-life and 89% seen in humans, reflecting species differences. [Verification: the human ~89% / ~1-week values are external FDA/clinical-pharmacology context, NOT from the cited rat study.]

Not a marketed or clinical dosing route — a pharmacological reference dose for bioavailability calculation only, in both the human and animal literature.

A common systemic dosing route in rodent (mouse) metabolic/mechanistic efficacy studies — e.g. high-fat-diet-induced-obesity models — not a human or approved route.

Bioavailability: No dedicated IP pharmacokinetic/bioavailability characterization was located; IP is used as a laboratory dosing route in mouse efficacy studies (doses reported ~10–100 μg/kg every other day over several weeks) rather than as the subject of its own PK study.

A laboratory-animal administration route, cited only to describe how some preclinical mechanistic/metabolic work was conducted. No human dosing implied.

Animal & human figures are kept visibly separate so studied animal doses are never misread as human guidance.

Sorted A–Z by vendor — never by price

Weekly median $/mg from the live vendor crawl.

Researched storefront prices, bucketed

p25 $5.70 · median $8.50 · p75 $12.50 · 11 researched vendors

Legit, COA-backed band: $5.00–$14.00/mg.

Value rule: don't just buy the cheapest — a price under $3/mg is a red flag. Pair price with COA and independent-test grade.

Estimated cost of research (10 mg)

Vial (best researched price)

$33

Bacteriostatic water (generic estimate)

$6

Syringes / supplies (generic estimate)

$12

What each test proves — general guidance, plus this compound's researched purity data

Purity on the current market (researched)

The research-peptide grey market and the counterfeit-branded-drug market show very different profiles. Finnrick's crowdsourced aggregate (a Layer-B testing/rating platform, ~279 semaglutide samples across 47 vendors as of ~Nov 2025) puts research-labeled purity at 88.19%–100.00%, with individual-vial fill diverging from the advertised quantity by up to ±488% at the extremes. Separately, a peer-reviewed test-purchase study of UNBRANDED illicit online sellers (Ashraf et al., J Med Internet Res, 7 Nov 2024; PMID 39509151) — a distinct, non-research-peptide channel — found purity of only 7.7%–14.37% against a 99% label claim, with endotoxin in all samples; note total semaglutide CONTENT actually exceeded labeled amounts by ~28.6–38.7% (impure, not under-dosed), and the tested items were unbranded illicit semaglutide, not counterfeit branded Ozempic. [Verification — softened: a self-published blog investigation (thepeptidelist.com, Jan 2026) reporting that an UNNAMED 'Tier-4' vendor's 'semaglutide' returned ~2,847 Da (vs semaglutide's true ~4,113 Da) is single-source Layer-B UGC about an anonymous vendor with no published COA and the blog's own proprietary 'Tier' ranking — refuted as an asserted counterfeit FACT and NOT attributable to any vendor; recorded here only as an uncorroborated caution, never as an established quality finding.]

Independent labs cited for this compound

No FDA Class I/II/III product recall of semaglutide was found (2023–2026). Genuine manufacturer product has not been recalled for a defect; instead FDA action takes the form of counterfeit-supply-chain alerts (the fakes are the problem, not the authentic product), warning letters to unapproved-drug sellers, an import alert, and — for Novo Nordisk itself — a pharmacovigilance/adverse-event-reporting warning letter. Reported honestly as an empty formal-recall result, not invented.

Buyer red-flag checklist

• No batch-specific COA provided on request (assume underdosed, off-target, or contaminated).
• COA is purity-only with no LC-MS/mass-spec identity confirmation — identity, not just purity, is what distinguishes real semaglutide from a wrong or degraded compound.
• Vial lot number doesn't match the lot printed on the COA.
• No endotoxin (LAL) or sterility data for a product implied for injection.
• Marketing that calls a research-labeled product a 'generic' or claims the 'same active ingredient' as Ozempic/Wegovy/Rybelsus — the specific false-or-misleading claim behind FDA's Sept 2025 50+-letter campaign.
• Human-dosing, weight-loss or appetite-suppression marketing copy on a 'research use only' site — the pattern drawing FDA warning letters throughout 2024–2026.
• No dosing/measurement guidance or appropriate syringe with a multi-dose vial — the mg/mL/unit-confusion pattern behind FDA's Jul 2024 overdose alert.
• Price far below the market median for the mg size (consistent with underfilled or off-spec product).

GMP vs research-grade: the chemistry (SPPS + HPLC + MS) is identical — the difference is the quality system.

Underdosing / mislabeling: A syndicated report on Finnrick's testing program states 'roughly one-third' of the thousands of peptide products it has tested (semaglutide/Wegovy used as the framing example) fail at least one of identity, purity (<98%), or quantity (vial-fill) checks. IMPORTANT: this is a CROSS-PEPTIDE market aggregate, NOT a semaglutide-isolated figure, and Finnrick is a testing/rating platform that outsources assays to third-party labs (e.g. Krause Analytical), not a lab itself. Semaglutide-specific Finnrick data (279 samples / 47 vendors) shows vial-fill divergence up to ±488% at the extremes rather than a clean single failure rate; an independent Janoshik program reported a comparable ~43% purity-fail rate across 2024 samples (per a Guardian investigation). A much higher, separate failure profile (~100% substandard, purity 7.7–14.37%) applies specifically to illegal online pharmacies selling unbranded/counterfeit semaglutide (Ashraf et al., JMIR 2024) — a different market segment than research-labeled vial sellers.

• Import Alert 66-80 authorizes detention-without-physical-examination of GLP-1 receptor agonist bulk drug substances — explicitly including semaglutide (plus tirzepatide, liraglutide, exenatide, dulaglutide) — from any manufacturer not on FDA's 'Green List' of verified CGMP-compliant foreign facilities. Research-labeled semaglutide sold outside that verified chain can also fall under the older, broader Import Alert 66-41 (detention of unapproved new drugs). An RUO label is not an import exemption — CBP judges actual intended use. [Verification: FDA press-launched the Green List concept Sep 5, 2025; the FDA Import Alert page carries an initial Published Date of 09/05/2025 (later majorly revised 06/22/2026), while some legal summaries date the formal 66-80 issuance Sep 19, 2025 — treat the exact issuance date as September 2025 pending a primary re-check.]66-80 (GLP-1 Green List) + 66-41 (unapproved new drugs)
• An RUO label is not an import exemption — CBP judges actual intended use.
• Lyophilized powder is ambient-stable in transit; temperature control needed for > 7-day transit.
• US-warehouse vendors dodge import scrutiny — they cost more but ship more reliably.

Every item dated & sourced

NOT on the WADA Prohibited List and NOT in category S4 (Hormone & Metabolic Modulators). Under the 2026 List cycle (in force 1 Jan 2026) semaglutide is on WADA's Monitoring Program — surveillance only; a positive marker is not an anti-doping-rule violation and no Therapeutic Use Exemption is required. USADA states GLP-1 agonists are 'not prohibited in sport.' [Verification: semaglutide has been monitored since 2024 — the 2026 change ADDED tirzepatide markers alongside it; circulating vendor/SEO claims that GLP-1 agonists moved to full 'S4' prohibition in Jan 2026 are REFUTED against WADA/NADA and USADA guidance. WADA has signaled it may CONSIDER prohibiting GLP-1 agonists ahead of LA 2028, but no prohibition is in effect for 2026.]

No granted patents identified in current seed. Composition-of-matter coverage is limited given the peptide's synthetic origin.

• IACUC / IRB research context
• RUO buyer responsibilities & documentation
• Veterinary / alternative-use where lawful
• Jurisdiction-aware "who may lawfully obtain"

What people discuss

Reported concerns — discussion, not established effects

Reading caveats

• Before/after transformation and influencer content skew visible sharing toward success stories
• Individual-account sentiment on X trends more negative than organizational/brand-account sentiment (framing/selection bias)
• Cost-and-access frustration tied to the 2025 compounding-shortage resolution may inflate negative-leaning threads independent of the drug's own effects
• Vendor/affiliate-seeded 'best source' content and astroturfing documented in peptide-sourcing subreddits and blogs
• Celebrity/political framing on X drives high-engagement posts that are cultural commentary, not patient experience
• Self-report side-effect studies cannot establish causation — posters may attribute unrelated symptoms to the drug
• Reported-concern shares derive from a large Reddit analysis pooling semaglutide AND tirzepatide (GLP-1 class) on a non-representative population — associational, not semaglutide-isolated causal side-effect rates

Manually researched from reddit, youtube, x— theme weights are research estimates, not live counts; aggregated & de-identified. No individual posts, quotes, or usernames are ever shown.

Relative research / market volume — populated once the activity stream is wired

Inline tooltips for lyophilized, RUO, EU/mg, SPPS, 503A and more.

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Long-acting GLP-1 receptor agonist approved for type 2 diabetes and obesity; once-weekly injection (Ozempic/Wegovy) or once-daily oral tablet (Rybelsus). Approximately 4,849 articles are indexed (literature last scanned 2026-05-29). US regulatory status: FDA-approved prescription drug; commercially available under multiple branded formulations. Research use only.

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