Everything below concerns reference standard. We keep the language plain, cite what the science says, and separate well-supported claims from open questions.
Last reviewed on 2026-01-14. Where a claim depends on a specific study, the study is described rather than over-claimed.
Clinical development of this compound followed earlier short-acting GLP-1 analogues that required frequent injection. Once-weekly subcutaneous formulations entered use after 2017, and an oral formulation using a permeation enhancer later became available. The oral version pairs the peptide with sodium N-(8-[2-hydroxybenzoyl] amino) caprylate, a carrier that improves uptake across the gastric epithelium. Interest has expanded from glycaemic control into weight management and metabolic liver disease. Regulatory status and approved indications differ between countries, and the product remains subject to ongoing safety monitoring.
Semaglutide is a synthetic peptide that acts as an agonist at the glucagon-like peptide-1 receptor. It is a structural analogue of human GLP-1(7-37), modified to resist enzymatic degradation by dipeptidyl peptidase-4. The peptide backbone contains alpha-aminoisobutyric acid at position 8, a substitution that stabilises the helix and slows cleavage. A fatty diacid side chain attached through a linker at lysine 34 promotes binding to serum albumin, which extends the circulating half-life. These two modifications together allow less frequent administration than native GLP-1 requires.
Activation of the GLP-1 receptor couples to Gs signalling and raises intracellular cyclic AMP in pancreatic beta cells. The resulting insulin release depends on prevailing glucose concentrations, so the effect is greater when glucose is elevated. Receptor engagement also suppresses glucagon secretion and slows gastric emptying, which flattens post-meal glucose excursions. In the central nervous system, signalling in hypothalamic and brainstem regions is associated with reduced appetite and lower energy intake. Studies continue to examine effects on cardiac, renal and hepatic endpoints; whether those benefits are independent of weight change remains an open question.
Certificate of analysis documents from suppliers typically report purity by chromatographic area, water content, and counter-ion identity. Independent verification is advisable because reported values can be generated under differing conditions. Impurity profiles matter for research use, where aggregates, deamidation products, and residual solvents may influence experimental results. Container, lot, and chain-of-custody records support traceability. Analytical results are method-dependent, so comparisons between laboratories require the same procedure and reference standards.
Lyophilized peptide material is typically stored at or below -20 °C, with -80 °C used for longer-term archives. Vials should remain sealed and desiccated because moisture promotes aggregation and hydrolysis. Repeated freeze-thaw cycles are avoided since they can alter peptide conformation and reduce recovery. Once reconstituted, solutions are generally kept at 2-8 °C and used within a defined window. Stability beyond those windows depends on buffer composition and concentration, and exact limits are product-specific rather than universal.
Identity and purity are assessed with reversed-phase high-performance liquid chromatography, which separates the peptide from related impurities by hydrophobicity. Mass spectrometry confirms molecular weight and detects truncation or modification products. Peptide mapping after enzymatic digestion verifies the amino acid sequence. Quantitation is often performed by LC-MS/MS or by immunoassay, and the two approaches can give different values because they measure different things. Method validation parameters such as accuracy, precision, and limit of quantitation are reported alongside results.
| Property | Value | Notes |
|---|---|---|
| Molecular formula | C187H291N45O59 | Parent peptide; salt forms also reported |
| Molecular mass | about 4113.6 Da | Average mass of the free peptide |
| Peptide length | 31 amino acids | Backbone related to GLP-1(7-37) |
| Key substitution | Aib at position 8 | Blocks DPP-4 cleavage |
| Albumin binding | Via C-18 diacid side chain | Prolongs circulation time |
Large randomised trials in adults with type 2 diabetes and in adults with obesity have reported reductions in body weight and improvements in several cardiovascular risk markers. One outcome trial found a lower incidence of major adverse cardiovascular events in participants with diabetes and established cardiovascular disease. Gastrointestinal effects such as nausea and vomiting are the most frequently reported adverse events and often diminish over time. Changes in lean body mass during weight loss are an area of ongoing investigation. Effects in adolescents and in pregnancy are less well characterised, and current labelling advises against use during pregnancy.
Semaglutide is a synthetic peptide analogue of glucagon-like peptide-1, a gut hormone released after nutrient intake. The molecule contains 31 amino acid residues and differs from the native sequence at several positions. A non-natural residue at position eight resists the enzyme that normally truncates the hormone, while a lysine-linked fatty diacid side chain promotes binding to serum albumin. These two modifications extend the circulating half-life from minutes to roughly one week. The peptide is produced by solid-phase synthesis followed by selective acylation, and its identity and purity are confirmed by spectrometric and chromatographic techniques.
The primary target is the GLP-1 receptor, a class B G protein-coupled receptor expressed on pancreatic beta cells, in the gut, and in several brain regions. Receptor activation raises intracellular cyclic AMP, which potentiates glucose-dependent insulin secretion and lowers glucagon release when blood glucose is elevated. Signalling in the hypothalamus and brainstem is associated with reduced appetite and slower gastric emptying. Because the insulinotropic effect depends on prevailing glucose levels, the hypoglycaemic risk of the peptide alone is described as low in most study settings. The relative contribution of peripheral and central actions remains an active research question.
Development began in the early 2010s with the goal of extending GLP-1 activity beyond the brief window achieved by native peptide infusion. The earliest approved formulation was a subcutaneous injection given once weekly. A later oral tablet pairs the peptide with an absorption enhancer, sodium N-(8-[2-hydroxybenzoyl] amino) caprylate, usually shortened to SNAC. That carrier lowers local pH and helps the peptide cross gastric tissue. Both routes deliver the same active molecule.
Semaglutide is a synthetic peptide analog of human glucagon-like peptide-1, a gut hormone released after meals. Its backbone retains the GLP-1 sequence but incorporates two substitutions that slow enzymatic breakdown by dipeptidyl peptidase-4. A short polyethylene glycol linker and a C18 fatty diacid are attached to the peptide chain, allowing the molecule to bind serum albumin and remain in circulation far longer than the native hormone. The result is a circulating half-life measured in days rather than the minutes typical of endogenous GLP-1.
Receptor activation occurs at GLP-1 receptors distributed across pancreatic islets, the hypothalamus, and the gastrointestinal tract. Binding triggers G protein signaling that raises cyclic AMP and enhances glucose-dependent insulin release. Because the effect depends on prevailing glucose levels, insulin secretion does not rise when blood sugar is already low. Signaling in the brain and gut also influences appetite and gastric emptying, which is why the compound appears in both metabolic and weight-related research literature.
皮下注射后吸收相对缓慢，绝对生物利用度约为百分之八十九，血药浓度峰值通常出现在给药后一到三天。与白蛋白结合使清除减慢，终末半衰期约为一百六十五小时，接近一周。连续给药约四到五周后达到稳态暴露水平。表观分布容积约为每千克零点二五升，血浆蛋白结合率超过百分之九十九。代谢以蛋白水解切割和脂肪二酸侧链的 β-氧化为主，相关产物主要经尿液与粪便排出。
序列层面的改动同时解决了两个问题，即酶解稳定性与肾脏清除速度。天然 GLP-1 在循环中的半衰期仅约两分钟，主要被二肽基肽酶-4 迅速灭活。酰化侧链与白蛋白的可逆结合形成循环储库，使分子缓慢释放并持续激活受体。这种设计思路后来被广泛用于同类长效肽的开发，属于该类药物化学改造的典型范式。
Semaglutide 是一种经结构修饰的胰高血糖素样肽-1 类似物，其主链与内源性 GLP-1(7-36) 约有百分之九十四的序列一致性。第 8 位丙氨酸被 α-氨基异丁酸取代，使二肽基肽酶-4 无法识别原有切割位点。第 34 位赖氨酸换为精氨酸，进一步降低酶解速率。第 26 位赖氨酸经间隔基连接一条含十八个碳的二酸脂肪链，该侧链赋予分子与血浆白蛋白结合的能力。
Quality control relies on pharmacopoeial monographs where they exist, combined with in-house specifications for identity, purity, water content, and counter-ion composition. Reference standards allow calibration across laboratories, although certified materials for every analogue are not universally obtainable. Batch records, chromatograms, and mass spectra form the documentation trail. Regulatory classification varies by jurisdiction and intended use, and research-grade material differs from pharmaceutical-grade material in testing scope. Analytical uncertainty is often expressed as relative standard deviation across replicate injections.
Lyophilised semaglutide is generally held at -20 °C or below, protected from light and moisture. Reconstituted solutions are typically kept at 2-8 °C and used within a defined window because degradation accumulates over time. Repeated freeze-thaw cycles are discouraged, since each cycle can promote aggregation and reduce monomeric content. Room-temperature stability of the solid has been examined in some studies but remains incompletely characterised for long durations, so cold storage is the conservative default for research material.
Degradation proceeds along several parallel routes. Deamidation of asparagine and glutamine residues generates charged variants that shift retention time in chromatographic analysis. Oxidation targets methionine and can be accelerated by trace metals or dissolved oxygen. Non-covalent aggregation produces dimers, oligomers, and larger species that are difficult to reverse. Isomerisation at aspartate residues is slower but measurable under thermal stress. The distribution among these pathways depends on pH, buffer composition, ionic strength, and the presence of excipients such as sugars or surfactants.
=== Advanced treatment plant technology === For some emerging contaminants, several advanced technologies—sonolysis, photocatalysis, Fenton-based oxidation and ozonation—have treated pollutants in laboratory experiments. Another technology is "enhanced coagulation" in which the treatment entity would work to optimize filtration by removing precursors to contamination through treatment. In the case of THMs, this meant lowering the pH, increasing the feed rate of coagulants, and encouraging domestic systems to operate with activated carbon filters and apparatuses that can perform reverse osmosis. Although these methods are effective, they are costly, and there have been many instances of treatment plants being resistant to pay for the removal of pollution, especially if it wasn't created in the water treatment process as many EC's occur from runoff, past pollution sources, and personal care products. It is also difficult to incentivize states to have their own policies surrounding contamination because it can be burdensome for states to pay for screening and prevention processes. There is also an element of environmental injustice, in that lower income communities with less purchasing and political power cannot buy their own system for filtration and are regularly exposed to harmful compounds in drinking water and food. However, recent treads for light-based systems shows great potential for such applications. With the decrease in cost of UV-LED systems and growing prevalence of solar powered systems, it shows great potential to remove CEC while keeping costs low.
== Rolfing == Schleip has been a rolfing instructor since 1988 and maintains a part-time private practice in Munich. He served as a member on the board of directors for the European Rolfing Association in Munich from 1995 to 1999, and on the ethics committee from 1999 to 2003, as well as a member of the international advisory board of the Rolf Institute in Boulder from 2000 to 2005. In 2006, he became the research director of the European Rolfing Association. He also is vice president of Ida P. Rolf Research Foundation In 2013, he received the RISI Award for "Excellence in Research" by the Rolf Institute.
The legal status of psilocybin mushrooms varies worldwide. Psilocybin and psilocin are listed as Class A (United Kingdom) or Schedule I (US) drugs under the United Nations 1971 Convention on Psychotropic Substances. The possession and use of psilocybin mushrooms, including P. semilanceata, is therefore prohibited by extension. Although many European countries remained open to the use and possession of hallucinogenic mushrooms after the US ban, starting in the 2000s (decade) there has been a tightening of laws and enforcements. In the Netherlands, where the drug was once routinely sold in licensed cannabis coffee shops and smart shops, laws were instituted in October 2008 to prohibit the possession or sale of psychedelic mushrooms—the final European country to do so. They are legal in Jamaica and Brazil and decriminalised in Portugal. In the United States, the city of Denver, Colorado, voted in May 2019 to decriminalize the use and possession of psilocybin mushrooms. In November 2020, voters passed Oregon Ballot Measure 109, making Oregon the first state to both decriminalize psilocybin and also legalize it for therapeutic use. Ann Arbor, Michigan, and the county it resides in have decriminalized magic mushrooms. Possession, sale and use are now legal within the county. In 2021, the City Councils of Somerville, Northampton, Cambridge, Massachusetts, and Seattle, Washington, voted for decriminalization.
==== Asia ==== Under Xi, China initially took a more critical stance on North Korea due to its nuclear tests. However, starting in 2018, the relations started to improve due to meetings between Xi and North Korean leader Kim Jong Un. Xi has initially improved relationships with South Korea, and the two countries signed a free-trade agreement in December 2015. Starting in 2017, China's relationship with South Korea soured over the Terminal High Altitude Area Defence (THAAD), a missile defense system, deployment of the latter, but improved after South Korea halted further deployments on the THAAD. China–Japan relations have initially soured under Xi's administration; the most thorny issue between the two countries remains the dispute over the Senkaku Islands, which China calls Diaoyu. However, the relations later started to improve, though deteriorated in 2025 after comments made by Prime Minister Sanae Takaichi regarding a potential defense of Taiwan. Since Xi came to power, China has been rapidly building and militarizing islands in the South China Sea, a decision Study Times of the Central Party School said was personally taken by Xi. Relations between China and India had ups and downs under Xi. The two countries had a standoff in Depsang in 2013, and again had a standoff over a Chinese construction of a road in Doklam, a territory both claimed by Bhutan, India's ally, and China, in 2017. The most serious crisis in the relationship came when the two countries had a deadly clash in 2020 at the Line of Actual Control, leaving some soldiers dead.
== Translation of NPU definitions == The English NPU definition structure allows for easy and reliable translation of the NPU definitions into other languages; translating each term in the structured NPU definition into another language will produce a valid definition in that language. The concept behind each term in the definition can be determined and agreed on by accessing the international code assigned to that term. The place of the concept in the syntax assigns the specific meaning of the concept in relation to the examination result. Translations of the NPU terminology are directly available in Danish and Swedish. The terminology has been structured such that translations into other languages is straightforward.
Sources: en.wikipedia.org
=== Nausea and vomiting === Tolerance to nausea occurs within 7–10 days, during which antiemetics (e.g. low dose haloperidol once at night) are very effective. Due to severe side effects such as tardive dyskinesia, haloperidol is now rarely used. A related drug, prochlorperazine is more often used, although it has similar risks. Stronger antiemetics such as ondansetron or tropisetron are sometimes used when nausea is severe or continuous and disturbing, despite their greater cost. A less expensive alternative is dopamine antagonists such as domperidone and metoclopramide. Domperidone does not cross the blood–brain barrier and produce adverse central antidopaminergic effects, but blocks opioid emetic action in the chemoreceptor trigger zone. This drug is not available in the U.S. Some antihistamines with anticholinergic properties (e.g. orphenadrine, diphenhydramine) may also be effective. The first-generation antihistamine hydroxyzine is commonly used, with the added advantages of not causing movement disorders, and also possessing analgesic-sparing properties. THC relieves nausea and vomiting; it also produces analgesia that may allow lower doses of opioids with reduced nausea and vomiting.
This was subsequently transferred to Innate Pharma in March 2020. On 10 December 2020, the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) adopted a positive opinion, recommending the granting of a marketing authorization under exceptional circumstances for the medicinal product Lumoxiti, intended for the treatment of relapsed or refractory hairy cell leukemia after two prior systemic therapies including a purine nucleoside analog. The orphan designation for Lumoxiti for treatment of hairy cell leukaemia was also maintained. The applicant for this medicinal product is AstraZeneca AB. Moxetumomab pasudotox was approved for medical use in the European Union in February 2021. The EU marketing authorization was withdrawn in July 2021.
===== Scotland ===== There are four NHS Scotland Gender Identity Clinics providing services to adults and a separate service for younger people. The National Gender Identity Clinical Network for Scotland reported in 2021 that some patients had waited in excess of two years from referral for their first appointment. Minister for Public Health Maree Todd has stated that the Scottish Government wants to reduce "unacceptable waits to access gender identity services". Research has indicated patient dissatisfaction with long wait times. However, overall experience of treatment outcomes was largely positive, particularly for hormone therapy and surgery.
== History of human tissue == In humans with non-injured tissues, the tissue naturally regenerates over time; by default, new available cells replace expended cells. For example, the body regenerates a full bone within ten years, while non-injured skin tissue is regenerated within two weeks. With injured tissue, the body usually has a different response. This emergency response usually involves building a degree of scar tissue over a time period longer than a regenerative response, as has been proven clinically and via observation. There are many more historical and nuanced understandings about regeneration processes. In full thickness wounds that are under 2 mm, regeneration generally occurs before scarring. In 2008, in full thickness wounds over 3 mm, it was found that a wound needed a material inserted in order to induce full tissue regeneration. Whereas third degree burns heal slowly by scarring, in 2016 it was known that full thickness fractional photothermolysis holes heal without scarring. Up to 40% of full thickness skin can be removed without scarring in an area, in a fractional pattern via coring of tissue. Some human organs and tissues regenerate rather than simply scar, as a result of injury. These include the liver, fingertips, and endometrium. More information is now known regarding the passive replacement of tissues in the human body, as well as the mechanics of stem cells. Advances in research have enabled the induced regeneration of many more tissues and organs than previously thought possible.
Memphis was the smallest of Northwest Airlines' three domestic hubs. The carrier utilized all the gates in Concourse B, as well as some in A and C. As of 2004, it operated about 210 daily flights to more than 80 destinations. The airport had mainline flights to cities such as Boston and San Francisco. Northwest Airlink flew to communities within Tennessee and across the South, like Baton Rouge and Chattanooga. The hub had international service to three countries in North America and one in Europe. Northwest offered a daily flight to Amsterdam; it had replaced KLM on the route in 2003. Other destinations included Montego Bay and Toronto. The hub's shortest flight was the one to Tupelo, Mississippi, on Saab 340 turboprops, while the longest was the DC-10 service to Amsterdam. Northwest was acquired by Delta Air Lines in 2008. Delta maintained Memphis as a hub, offering 240 flights per day in 2009. However, due to high fuel costs, the company made Memphis subordinate to its hub in Atlanta. The airport's role changed to handling traffic that exceeded Atlanta's capacity, and flights were gradually scaled back. Delta discontinued the Amsterdam link in September 2012; as the hub shrank, so did the amount of connecting traffic that supported the flight. The following year, Pinnacle Airlines Corp. moved its headquarters out of the city. The holding company owned Pinnacle Airlines, formerly known as Express Airlines I. Delta closed the hub in September 2013, decreasing the number of daily departures from 94 to 60.
Sources: en.wikipedia.org
=== Clinical safety === Early clinical trials with DMSO were stopped because of questions about its safety, especially its ability to harm the eye. The most commonly reported side effects include headaches and burning and itching on contact with the skin. Strong allergic reactions have been reported. On September 9, 1965, The Wall Street Journal reported that a manufacturer of the chemical warned that the death of an Irish woman after undergoing DMSO treatment for a sprained wrist may have been due to the treatment, although no autopsy was done, nor was a causal relationship established. Clinical research using DMSO was halted and did not begin again until the National Academy of Sciences (NAS) published findings in favor of DMSO in 1972. In 1978, the US FDA approved DMSO for treating interstitial cystitis. In 1980, the US Congress held hearings on claims that the FDA was slow in approving DMSO for other medical uses. In 2007, the US FDA granted "fast track" designation on clinical studies of DMSO's use in reducing brain tissue swelling following traumatic brain injury. DMSO exposure to developing mouse brains can produce brain degeneration. This neurotoxicity could be detected at doses as low as 0.3 mL/kg, a level exceeded in children exposed to DMSO during bone marrow transplant.
=== Image production === Images are constructed by plotting ion intensity versus relative position of the data from the sample. Spatial resolution highly impacts the molecular information gained from analysis.
Garcia E, Rhee SG (1983). "Cascade control of Escherichia coli glutamine synthetase Purification and properties of PII uridylyltransferase and uridylyl-removing enzyme". J. Biol. Chem. 258 (4): 2246–53. doi:10.1016/S0021-9258(18)32914-4. PMID 6130097. van Heeswijk WC, Rabenberg M, Westerhoff HV, Kahn D (1993). "The genes of the glutamine synthetase adenylylation cascade are not regulated by nitrogen in Escherichia coli". Mol. Microbiol. 9 (3): 443–57. doi:10.1111/j.1365-2958.1993.tb01706.x. PMID 8412694. S2CID 8691388.
== Biosynthesis == The biosynthesis of eugenol begins with the amino acid tyrosine. L-tyrosine is converted to p-coumaric acid by the enzyme tyrosine ammonia lyase (TAL). From here, p-coumaric acid is converted to caffeic acid by p-coumarate 3-hydroxylase using oxygen and NADPH. S-Adenosyl methionine (SAM) is then used to methylate caffeic acid, forming ferulic acid, which is in turn converted to feruloyl-CoA by the enzyme 4-hydroxycinnamoyl-CoA ligase (4CL). Next, feruloyl-CoA is reduced to coniferyl aldehyde by cinnamoyl-CoA reductase (CCR). Coniferyl aldehyde is then further reduced to coniferyl alcohol by cinnamyl-alcohol dehydrogenase (CAD) or sinapyl-alcohol dehydrogenase (SAD). Coniferyl alcohol is then converted to an ester in the presence of the substrate CH3COSCoA, forming coniferyl acetate. Finally, coniferyl acetate is converted to eugenol via the enzyme eugenol synthase 1 and the use of NADPH. Eugenol is a metabolite of caleicine, the active compound found in Calea ternifolia, and is thought to cause the sedative and hallucinogenic state C. ternifolia can induce.
For services to Child Road Safety. Kenneth Fitzpatrick. Lifeboat Operations Manager, Porthdinllaen Lifeboat Station, Royal National Lifeboat Institution. For services to Maritime Safety. Barry Flack. For services to the Jewish Community in the London Borough of Barnet. Margaret Elizabeth Flanagan. Member, Inner Wheel Club of Ballymena. For voluntary services to the community in Ballymena, County Antrim. John Campbell Forrester. President and Poppy Appeal Organiser, Driffield Branch, Royal British Legion. For voluntary service to Veterans in East Yorkshire. Claire Forsythe. Duke of Edinburgh's Award Officer, Probation Board for Northern Ireland. For services to the Rehabilitation of Offenders. Susan Joan Foster. For voluntary service in Hampshire. Richard Charles Fowler. Library Lead, Harbury Community Library, Warwickshire. For services to Libraries. Dr Jennifer Ann Frow. Volunteer, Bewdley Tennis Club. For services to Lawn Tennis in Worcestershire. Robert Francis Fyfe. Chair and Director, Runway Theatre Company. For services to the Arts and to the community in Glasgow. Melanie Jane Gardner. Fine and Decorative Arts Curator, Tullie House Museum, Carlisle. For services to Arts and Culture in Cumbria. Joseph William Garvey. For services to the community in County Armagh. Peter William Garwood. For services to the community in Barrow-in-Furness, Cumbria. Christine Frances Gatfield. Founder, Dove Cottage Day Hospice. For services to the Terminally Ill. Patricia Mary Gaywood. Membership Secretary, The Forty Club. For voluntary service to Cricket. Andrew Gell.
Sources: en.wikipedia.org
It belongs to the incretin mimetic class and acts as a long-acting glucagon-like peptide-1 receptor agonist. The class includes several peptides with different half-lives and routes of administration.
The side chain enables reversible binding to albumin in the bloodstream, which protects the peptide from rapid renal clearance. This extends the interval between administrations compared with unmodified GLP-1.
No. It shares much of the native sequence but carries substitutions and an added side chain. These changes increase stability against enzymatic breakdown.
The lyophilized powder is dissolved in a suitable solvent, often sterile water or a buffered diluent, with gentle mixing rather than vigorous shaking. Foaming and shear should be avoided because they can promote aggregation. The resulting solution is then stored cold and protected from light.