This is a working overview of GLP-1 类似物, written for readers who want more than a one-paragraph summary but less than a textbook.
Reviewed 2026-01-12. Anything still debated is marked as such rather than presented as settled.
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.
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.
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.
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.
| Property | Value | Notes |
|---|---|---|
| Molecular class | Acylated GLP-1 receptor agonist | 31-residue synthetic peptide |
| Molecular formula | C187H291N45O59 | established for the free peptide |
| Appearance | White to off-white powder | as supplied before formulation |
| Solubility | Freely soluble in water | aqueous buffers near neutral pH |
| Typical storage | 2 to 8 degrees Celsius, protected from light | powder and solution forms differ in shelf life |
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。
该分子作为 GLP-1 受体的选择性激动剂发挥作用，受体属于 B 类 G 蛋白偶联受体家族，激活后经 Gs 通路提升细胞内环腺苷酸水平。在胰腺 β 细胞，信号促进葡萄糖依赖性的胰岛素释放，血糖偏低时该作用明显减弱。在胰岛 α 细胞，胰高血糖素分泌受到抑制。中枢神经系统与胃肠道同样存在受体表达，相应信号参与食欲调节以及胃排空速率的降低。
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。
Reverse-phase high-performance liquid chromatography with ultraviolet detection near 214 nm is the standard purity method, reported as area percent. Mass spectrometry, usually with electrospray ionisation, confirms identity and reveals covalent modifications. Size-exclusion chromatography quantifies aggregates and fragments. Peptide mapping after enzymatic digestion localises changes to specific sequence regions. Circular dichroism and infrared spectroscopy report on secondary structure, while light scattering tracks particle formation in liquid formulations. No single technique captures every quality attribute.
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.
Both morphine and 6-MAM are μ-opioid agonists that bind to receptors present throughout the brain, spinal cord, and gut of all mammals. The μ-opioid receptor also binds endogenous opioid peptides such as β-endorphin, leu-enkephalin, and met-enkephalin. Repeated use of heroin results in a number of physiological changes, including an increase in the production of μ-opioid receptors (upregulation). These physiological alterations lead to tolerance and dependence, so that stopping heroin use results in uncomfortable symptoms including pain, anxiety, muscle spasms, and insomnia called the opioid withdrawal syndrome. Depending on usage it has an onset 4–24 hours after the last dose of heroin. Morphine also binds to δ- and κ-opioid receptors. There is also evidence that 6-MAM binds to a subtype of μ-opioid receptors that are also activated by the morphine metabolite morphine-6β-glucuronide but not morphine itself. The third subtype of third opioid type is the mu-3 receptor, which may be a commonality to other six-position monoesters of morphine. The contribution of these receptors to the overall pharmacology of heroin remains unknown. A subclass of morphine derivatives, namely the 3,6 esters of morphine, with similar effects and uses, includes the clinically used strong analgesics nicomorphine (Vilan), and dipropanoylmorphine; there is also the latter's dihydromorphine analogue, diacetyldihydromorphine (Paralaudin).
Historically, it has been used in fermentation, specifically to ferment soybean and create tempeh in Malaysia and Indonesia. Using the same methods to create traditional tempeh, R. oryzae can be inoculated in other cooked legumes such as peas, beans, and fava beans. Similarly in tempeh making, there is an initial bacterial fermentation in legumes when they are soaked for a while before being cooked. Fermentation incubation lasts for 48 hours at 33 °C. After incubation, mycelium can be observed between the legumes creating a larger, uniform product. Overall, fruits, grains, nuts, and legumes mold-fermentation with R. oryzae produces sensory changes in foods such as creating acidity, sweetness and bitterness. R. oryzae can produce lactate from glucose at high levels, which is used as a food additive and can also degrade plastics. In enzyme-modified cheese products, R. oryzae provides microbial enzymes where milk fat and proteins are broken down to create powder and paste forms of cheese. Specifically, it breaks down cheese curds and acid casein. Among finding cellulases and hemicellulases, other enzymes such as protease, urease, ribonuclease, pectate lyase, and polygalacturonase are found in cultural media of R. oryzae. Besides producing a number of enzymes, it can also produce a number of organic acids, alcohol, and esters. Cellulases in R. oryzae can be applied to biotechnology, in food, brewery and wine, animal feed, textiles and laundry, pulp and paper industries, and agriculture. R.
Codeine became a prescription-only medication in the province of Manitoba on 1 February 2016. The number of low-dose codeine tablets sold in Manitoba decreased by 94 percent from 52.5 million tablets sold in the year prior to the policy change to 3.3 million in the year after. A pharmacist may issue a prescription, and all purchases are logged to a central database to prevent overprescribing. Saskatchewan's pharmacy college is considering enacting a similar ban to Manitoba's. On 9 May 2019, the Canadian Pharmacists Association wrote to Health Canada proposing regulations amending the NCR, the BOTSR, and the FDR - Part G, which included requiring that all products containing codeine be available by prescription only. New safety measures were issued by Health Canada on 28 July 2016; "codeine should no longer be used (contraindicated) in patients under 18 years of age to treat pain after surgery to remove tonsils or adenoids, as these patients are more susceptible to the risk of serious breathing problems. Codeine (prescription and non-prescription) is already not recommended for children under the age of 12, for any use."
Although progesterone does not have significant AR-mediated androgenic or antiandrogenic activity, it is a precursor and intermediate, albeit distant, in the biosynthesis of androgens from cholesterol. For this reason, there has been some speculation that exogenous progesterone could be transformed into androgens by certain tissues that express the requisite enzymes. Progesterone is converted by 17α-hydroxylase into 17α-hydroxyprogesterone; 17α-hydroxyprogesterone is converted by 17,20-lyase into androstenedione; and androstenedione is converted by 17β-hydroxysteroid dehydrogenases into testosterone. CYP17A1, the cytochrome P450 gene that encodes 17α-hydroxylase and 17,20-lyase, is expressed mainly in the gonads (ovaries and testes) and the adrenal glands. However, while it is theoretically possible that progesterone could be transformed in the body into androgens, no androgenic effects have been observed in animal studies. In addition, clinical studies, in which women were treated with 100 to 300 mg/day oral progesterone, have found no or only a small increase in levels of 17α-hydroxyprogesterone, and no change in androgen levels, including of dehydroepiandrosterone, androstenedione, and testosterone. In these studies, levels of estradiol and cortisol, which progesterone is also a precursor of, did not change either, although levels of 11-deoxycorticosterone increased significantly.
Sources: en.wikipedia.org
=== Divergences with A&W (Great American Brand) === The Canadian menu diverges significantly from their international counterparts franchised through A Great American Brand. This divergence is due to the brand's separate management and ownership. The only Burger Family product available by name in U.S. locations is the Papa Burger. The Papa Burger differs significantly between Canada and the U.S. Notable products on the U.S. menu not available in Canada include deep-fried cheese curds and soft serve-based products such as sundaes.
September 15 The US military announces that it destroyed two Iranian small boats the day before following an IRGC attempt to capture one of its Navy drones patrolling the Strait of Hormuz. A federal judge blocks the Kennedy Center from adding President Trump's name to the building or its grounds without congressional approval. Hours later, the centre's board votes to close most of the venue for up to two years for renovations. September 16 Three people are killed in a helicopter crash in Chatsworth, Los Angeles, including NBC News journalists Eliana Moreno and George Marciniw. The Federal Reserve raises interest rates for the first time in three years, from 3.5%-3.75% to 3.75%-4%. A memorandum of understanding is signed with the Pakistan army by US drone maker Powerus, which is set to merge with a firm backed by Trump’s sons. The Trump administration announces that Palestinian president Mahmoud Abbas and his delegation are barred from attending the UN General Assembly in New York, accusing them of breaching US law. September 17 The House of Representatives passes sweeping Russia sanctions legislation by a vote of 262-159. Flash flooding in the Navajo Nation kills three. A UN mission finds grounds to believe that the US committed war crimes in the 2026 Minab school attack and the 2026 Lamerd sports hall attack.
Most modern nuclear weapons utilize 238U as a "tamper" material (see nuclear weapon design). A tamper which surrounds a fissile core works to reflect neutrons and to add inertia to the compression of the 239Pu charge. As such, it increases the efficiency of the weapon and reduces the critical mass required. In the case of a thermonuclear weapon, 238U can be used to encase the fusion fuel, the high flux of very energetic neutrons from the resulting fusion reaction causes 238U nuclei to split and adds more energy to the "yield" of the weapon. Such weapons are referred to as fission-fusion-fission weapons after the order in which each reaction takes place. An example of such a weapon is Castle Bravo. The larger portion of the total explosive yield in this design comes from the final fission stage fueled by 238U, producing enormous amounts of radioactive fission products. For example, an estimated 77% of the 10.4-megaton yield of the Ivy Mike thermonuclear test in 1952 came from fast fission of the depleted uranium tamper. Because depleted (or natural) uranium has no critical mass, it can be added to thermonuclear bombs in almost unlimited quantity. The Soviet Union's test of the Tsar Bomba in 1961 produced "only" 50 megatons of explosive power, over 90% of which came from fusion because the 238U final stage had been replaced with lead. Had 238U been used instead, the yield of the Tsar Bomba could have been well above 100 megatons, and it would have produced nuclear fallout equivalent to one third of the global total that had been produced up to that time.
Sources: en.wikipedia.org
Native GLP-1 is degraded within minutes by dipeptidyl peptidase-4 and neutral endopeptidases. Semaglutide carries a non-natural amino acid at position eight that blocks that cleavage, and a fatty diacid side chain that binds albumin. The result is a much longer duration of action than the native hormone.
The fatty diacid chain associates strongly with serum albumin, which keeps the peptide in circulation and shields it from rapid renal clearance. Bound peptide is released gradually, producing a sustained receptor signal. This mechanism also reduces the peak-to-trough variation seen with shorter-acting analogues.
The balance between peripheral receptor activation and signalling in the central nervous system is not fully resolved. The extent to which slowed gastric emptying accounts for reduced energy intake, compared with direct effects on appetite circuits, is debated. Long-term effects on lean mass and on tissues outside the gut and brain are still under study.
Native GLP-1 is degraded within minutes by circulating enzymes. The synthetic version carries substitutions at positions that block enzymatic cleavage, plus a fatty acid side chain that promotes albumin binding. These two changes together extend circulation time from minutes to roughly a week.