Everything below concerns body composition. We keep the language plain, cite what the science says, and separate well-supported claims from open questions.
Updated 2026-02-10. Numbers and descriptions here follow the published literature rather than marketing material.
Published information places retatrutide in clinical development rather than on the market as an approved therapy. Early-stage and mid-stage trials have examined tolerability and changes in body weight, and larger studies continue to report results over time. Open questions include the durability of effects after treatment stops, the composition of weight lost, and cardiovascular outcomes over long periods. Statements about definitive benefit should therefore be treated as provisional. Regulatory status varies by jurisdiction and changes as applications are reviewed.
Retatrutide is an investigational synthetic peptide designed to activate three distinct receptor systems within a single molecule. Its pharmacological profile combines activity at the glucose-dependent insulinotropic polypeptide receptor, the glucagon-like peptide-1 receptor, and the glucagon receptor. This arrangement places it within a broader class of agents often described as multi-agonists, which contrast with compounds that engage one or two targets. Research interest centers on whether simultaneous signaling produces effects that single-receptor agonists cannot achieve alone. A single molecular entity also simplifies manufacturing and delivery logistics compared with combining separate agents.
retatrutide 是一种人工合成的多肽，设计目标是同时作用于 GIP、GLP-1 与胰高血糖素三种受体。这种三重激动设计试图把多条代谢通路的调节整合进单一分子，而不是只依赖一种肠促胰素受体。分子骨架以天然肽序列为基础，经过非天然氨基酸替换和脂肪酸侧链修饰，以获得更长的作用时间。该方向属于多受体激动剂研究的一部分，与双重激动剂的工作并行推进。
三种受体在能量平衡中的分工并不相同：GLP-1 与 GIP 受体主要参与胰岛素分泌和食欲调节，胰高血糖素受体则与能量消耗及肝糖输出相关。同时激活三者可能产生叠加效应，也可能出现相互制约，具体结果取决于受体亲和力与组织分布。这种组合在理论上可能同时影响体重与血糖指标，但协同关系的细节仍处在研究阶段。
化学修饰延长了分子在体内的停留时间，使较低频次的给药安排成为可能。脂肪酸侧链通过与白蛋白结合延缓清除，非天然氨基酸则降低酶解速率。这些修饰同时改变分子的溶解性与稳定性，需要在制剂设计和储存条件中一并考虑。修饰引入的免疫原性风险也属于开发过程中需要评估的项目。
| Property | Value | Notes |
|---|---|---|
| Molecular class | Synthetic peptide | Studied for metabolic indications |
| Receptor activity | GIP, GLP-1, and glucagon | Single molecule, three targets |
| Development status | Investigational | Not an approved therapy |
| Common synonym | LY3437943 | Development designation |
| Administration route | Subcutaneous injection | As used in clinical studies |
Human evidence remains limited to controlled studies. A phase 2 trial in adults with obesity reported large, dose-dependent reductions in body weight over 48 weeks, with gastrointestinal events as the most frequently recorded adverse effect. Phase 3 programs designated TRIUMPH, for obesity, and TRANSCEND, for type 2 diabetes, are intended to confirm efficacy and to characterize safety in larger populations. Related studies are examining conditions such as knee osteoarthritis in people with obesity and metabolic liver disease. Open questions include long-term tolerability, effects on lean mass, and what happens after treatment is stopped.
Retatrutide is an investigational synthetic peptide that acts on three receptor targets at once: glucose-dependent insulinotropic polypeptide, glucagon-like peptide-1, and glucagon. It is developed by Eli Lilly and appears in the literature and in trial registries under the code LY3437943. The molecule belongs to a class of engineered peptides designed to resist rapid breakdown and permit infrequent subcutaneous administration. No regulatory agency has approved it for clinical use, and all available human data come from controlled trials rather than from routine practice.
Body composition is assessed with dual-energy X-ray absorptiometry or comparable methods, which separate fat mass from lean mass. Reported losses include both compartments, and the ratio between them is a subject of ongoing analysis rather than a settled result. Waist circumference, blood pressure, and lipid panels are collected as supporting measures. Resting energy expenditure and substrate oxidation are measured in smaller mechanistic studies, where glucagon receptor activity is expected to matter. These substudies are typically short and small, so their findings carry wide uncertainty.
Interpretation depends on study phase and duration. Phase 2 programs are powered for weight and safety signals, not for cardiovascular or renal outcomes, which require event-driven designs. Gastrointestinal events such as nausea, diarrhea, vomiting, and constipation are the most frequently reported adverse effects and tend to cluster around dose escalation. Small increases in heart rate have been described. Because follow-up after treatment discontinuation is limited, questions about weight regain and durability are open rather than answered.
与仅靶向单一受体的同类药物相比，瑞他鲁肽增加胰高血糖素受体成分，理论上可提高能量消耗并改变脂肪分布。临床中观察到的体重变化是否主要来自该额外机制，目前尚无定论。胃肠道反应是该类药物常见不良事件，试验中通过剂量递增和监测进行管理。停药后体重反弹、个体差异和长期耐受性仍需更多数据。
瑞他鲁肽是一种在研合成肽，同时作用于胰高血糖素样肽-1、葡萄糖依赖性促胰岛素多肽和胰高血糖素受体。该分子属于多受体激动剂类别，尚未获得任何监管机构的上市批准。当前临床开发主要针对肥胖和2型糖尿病，研究代号为LY3437943。已确立的信息包括受体靶点和部分中期试验结果；最终疗效、长期安全性和适用人群仍属开放问题。
=== Complications of executions and cessation of supply of lethal injection drugs === By early 2014, a number of botched executions involving lethal injection and a rising shortage of suitable drugs had some U.S. states reconsidering lethal injection as a form of execution. Tennessee, which had previously offered inmates a choice between lethal injection and the electric chair, passed a law in May 2014 that gave the state the option to use the electric chair if lethal injection drugs were either unavailable or declared unconstitutional. At the same time, Wyoming and Utah were considering the use of execution by firing squad in addition to other existing execution methods. In 2016, Pfizer joined over 20 American and European pharmaceutical manufacturers that had previously blocked the sale of their drugs for use in lethal injections, effectively closing the open market for FDA-approved manufacturers for any potential lethal execution drug. In the execution of Carey Dean Moore on August 14, 2018, the State of Nebraska used a novel drug cocktail comprising diazepam, fentanyl, cisatracurium, and potassium chloride, over the strong objections of the German pharmaceutical company Fresenius Kabi. Potassium acetate had been incorrectly used in place of potassium chloride in Oklahoma in January 2015 for the execution of Charles Frederick Warner. In August 2017, the State of Florida first used the drug in the execution of Mark James Asay using a combination of etomidate, rocuronium bromide, and potassium acetate as part of a new protocol.
== Transplantation and gene therapy == Hematopoietic stem cells (HSC) are cells in the bone marrow that can develop into all types of blood cells, including red blood cells, white blood cells, and platelets. There are two possible ways to treat hemoglobinopathies by targeting HSCs. One is to transplant HSCs from a healthy donor into the patient's bone marrow; this was pioneered in 1981. More recently, it has become possible to use CRISPR gene editing technology to modify the patient's own HSCs in a way that increases production of functional beta-globin chains, leading to near normal levels of healthy hemoglobin. All stem cell treatments must involve myeloablation of the patients' bone marrow in order to remove HSCs containing the faulty gene. This requires high doses of chemotherapy agents with side effects such as sickness and tiredness. A long hospital stay is necessary after infusion of the replacement HSCs while the cells take up residence in the bone marrow and start to make red blood cells with the stable form of haemoglobin.
Although bicalutamide monotherapy increases gonadotropin and sex hormone levels in men, this will not occur if bicalutamide is combined with an antigonadotropin such as a GnRH analogue, estrogen, or progestogen, as these medications maintain negative feedback on the HPG axis. NSAA monotherapy, including with bicalutamide, shows a number of tolerability differences from methods of androgen deprivation therapy that incorporate surgical or medical castration. For example, the rates of hot flashes, depression, fatigue, and sexual dysfunction are all much higher with GnRH analogues than with NSAA monotherapy. It is thought that this is because GnRH analogues suppress estrogen production in addition to androgen production, resulting in estrogen deficiency. In contrast, NSAA monotherapy does not decrease estrogen levels and in fact increases them, resulting in an excess of estrogens that compensates for androgen deficiency and allows for a preservation of mood, energy, and sexual function. Neurosteroids that are produced from testosterone like 3α-androstanediol and 3β-androstanediol, which are ERβTooltip estrogen receptor beta agonists and the former a potent GABAA receptor positive allosteric modulator, may also be involved. In the specific case of sexual dysfunction, an additional possibility for the difference is that without concomitant suppression of androgen production, blockade of the AR by the bicalutamide in the brain is incomplete and insufficient to markedly influence sexual function. Under normal circumstances, bicalutamide has no capacity to activate the AR.
Tranexamic acid is a medication used to treat or prevent excessive blood loss from major trauma, postpartum bleeding, surgery, tooth removal, nosebleeds, and heavy menstruation. It is also used for hereditary angioedema. It is taken either by mouth, injection into a vein, or by intramuscular injection. Tranexamic acid is a synthetic analog of the amino acid lysine. It serves as an antifibrinolytic by reversibly binding four to five lysine receptor sites on plasminogen. This decreases the conversion of plasminogen to plasmin, preventing fibrin degradation and preserving the framework of fibrin's matrix structure. Tranexamic acid has roughly eight times the antifibrinolytic activity of an older analogue, ε-aminocaproic acid. Tranexamic acid also directly inhibits the activity of plasmin with weak potency (IC50 = 87 mM), and it can block the active-site of urokinase plasminogen activator (uPA) with high specificity (Ki = 2 mM), one of the highest among all the serine proteases. Side effects are rare; they include changes in color vision, seizures, blood clots, and allergic reactions. Tranexamic acid appears to be safe for use during pregnancy and breastfeeding. Tranexamic acid was first made in 1962 by Japanese researchers Shosuke and Utako Okamoto. It is on the World Health Organization's List of Essential Medicines. Tranexamic acid is available as a generic drug.
Sources: en.wikipedia.org
=== Photo-chemically and electro-chemically active units === Porphyrins, and phthalocyanines have highly tunable photochemical and electrochemical activity as well as the potential to form complexes. Photochromic and photoisomerizable groups can change their shapes and properties, including binding properties, upon exposure to light. Tetrathiafulvalene (TTF) and quinones have multiple stable oxidation states, and therefore can be used in redox reactions and electrochemistry. Other units, such as benzidine derivatives, viologens, and fullerenes, are useful in supramolecular electrochemical devices.
For most people, 3.5 dried grams (1/8 oz) would be considered a high dose and may produce an intense experience; this is, however, typically considered a standard dose among recreational users. Body composition (usually weight) should be taken into account when calculating dosage. For many individuals, doses above three grams may be overwhelming. For a few rare people, doses as small as 0.25 gram can produce full-blown effects normally associated with very high doses. For most people, however, that dose level would have virtually no effects. There are many different ways to ingest Psilocybe cubensis. Users may prefer to take them raw, freshly harvested, or dried and preserved. It is also possible to prepare culinary dishes such as pasta or tea with the mushrooms. However, the psychoactive compounds begin to break down rapidly at temperatures exceeding 100 °C (212 °F). Another method of ingestion known as "Lemon Tekking" involves combining pulverized Psilocybe cubensis with a concentrated citrus juice with a pH of ~2. Many users believe that a considerable amount of the psilocybin will have been dephosphorylated into psilocin, the psychoactive metabolite, by citric acid. However, this claim is not substantiated by the literature on the metabolism of psilocybin, as dephosphorylation is known to be mediated by the enzyme alkaline phosphatase in humans. It is therefore more likely that citric acid mostly helps in breakdown of mushroom cells, aiding in digestion and psilocybin release.
== Global occurrence and sources == PFOA contaminates every continent. Two of the most common types of PFAS (more precisely, PFOS and PFOA) were phased out of production in the United States (US) in 2002 and 2015 respectively, but are still present in some imported products. PFOA and PFOS are found in every American person's blood stream in the parts per billion range, though those concentrations have decreased by 70% for PFOA and 84% for PFOS between 1999 and 2014, which coincides with the end of the production and phase out of PFOA and PFOS in the US. PFOA has been detected in the central Pacific Ocean at low parts per quadrillion ranges, and at low parts per trillion (ppt) levels in coastal waters. Due to the surfactant nature of PFOA, it has been found to concentrate in the top layers of ocean water. PFOA is detected widely in surface waters, and is present in numerous mammals, fish, and bird species. PFOA is in the blood or vital organs of Atlantic salmon, swordfish, striped mullet, gray seals, common cormorants, Alaskan polar bears, brown pelicans, sea turtles, sea eagles, Midwestern bald eagles, California sea lions and Laysan albatrosses on Sand Island, a wildlife refuge on Midway Atoll, in the middle of the North Pacific Ocean, about halfway between North America and Asia. Because PFAS are ubiquitous in households, consumer products, food, and the environment generally, some trace levels reflecting this ubiquitous broad use of these compounds will make their way into the wastewater and solid waste streams.
Tryptophan produces the head-twitch response (HTR) in rodents when administered at sufficiently high doses. The HTR is induced by serotonergic psychedelics like lysergic acid diethylamide (LSD) and psilocybin and is a behavioral proxy of psychedelic effects. Tryptophan is converted into the trace amine tryptamine and tryptamine is N-methylated by indolethylamine N-methyltransferase (INMT) into N-methyltryptamine (NMT) and N,N-dimethyltryptamine (DMT), which are known serotonergic psychedelics.
==== The cancelled meeting ==== In early December Thatcher had two ad hoc meetings with Heseltine, Brittan, Tebbit, William Whitelaw (Deputy Prime Minister), Geoffrey Howe (Foreign Secretary) and Nigel Lawson (Chancellor of the Exchequer). Howe and Tebbit were not unsympathetic to Heseltine's proposed consortium, and the decision was deferred to the Cabinet Economic Affairs Committee (E(A)) on Monday 9 December 1985. After that meeting Thatcher, who complained that three hours had been spent discussing a company with a market capitalisation of only £30m (a tiny amount in government terms), allowed Heseltine until 4pm on Friday 13 December to submit a viable proposal for a European deal. He did (with British Aerospace and GEC now part of his consortium), but Westland's directors rejected it. Heseltine had expected that there would be a second meeting of E(A) to discuss his consortium, but no such meeting was called; Thatcher later stated that the Monday meeting had agreed to leave the decision to Westland to take, but it later emerged that Ridley and Lord Young had placed such a meeting in their diaries and had been told by Number Ten that it had been cancelled. Heseltine threatened resignation for the first time. Heseltine raised his concerns with Tebbit, Whitelaw and John Wakeham (Chief Whip). At Cabinet on Thursday 12 December he had an angry exchange with Thatcher about the cancelled meeting, but Westland was not on the agenda for the meeting and Thatcher refused to permit a discussion on the matter, arguing that Cabinet could not do so without the necessary papers.
Sources: en.wikipedia.org
== Awards == Gold Medal of the Society for Magnetic Resonance in Medicine (1989) GE Coolidge Fellow and Medal, (1990) GE Gold (1989), Silver (1985) and Bronze (1982) patent medallions Editors recognition awards from Radiology (1986, 1988, 1989, 1990) GE Dushman Award (1983) Associate editor, Magn Reson Med (1983-2004), deputy editor (2010-2025) Editorial boards of Magn Reson Imag (1982–present), Rev Sci Instrum (1986-1988), and Radiology (1991-5) Editorial board of Advanced Medicine (Japan: 1995–); MAGMA (2003–2006) Elected trustee, Soc Magn Reson Med (1986-1989), and Soc Magn Reson Imag (1982-1986) Fellow, Soc Magn Reson (1989) Gold Medal of the American Roentgen Ray Society (2015) Distinguished investigator, Academy of Radiology Research (2012) Member, National Academy of Inventors (2015) Soc Magn Reson Med Sir Peter Mansfield Lecturer (2012) NIH grant reviewer since 1979
== Mechanical stress and activity indicators == Examining the effects that activities has upon the skeleton allows the archaeologist to examine who was doing what kinds of labor, and how activities were structured within society. Labor within the household may be divided according to gender and age, or be based on other social structures. Human remains can allow archaeologists to uncover these patterns. Living bones are subject to Wolff's law, which states that bones are physically affected and remodeled by physical activity or inactivity. Increases in mechanical stress tend to produce thicker and stronger bones. Disruptions in homeostasis caused by nutritional deficiency or disease or profound inactivity/disuse/disability can lead to bone loss. While the acquisition of bipedal locomotion and body mass appear to determine the size and shape of children's bones, activity during the adolescent growth period seems to exert a greater influence on the size and shape of adult bones than exercise later in life. Muscle or ligament attachment sites on bones (entheses) are also considered to be impacted by habitual biomechanical loading, leading to the occurrence of various entheseal changes. These changes are routinely used in the field to study activity-patterns.
=== Ecological consequences === During the 1982–83, 1997–98 and 2015–16 ENSO events, large extensions of tropical forests experienced a prolonged dry period that resulted in widespread fires, and drastic changes in forest structure and tree species composition in Amazonian and Bornean forests. Their impacts do not restrict only vegetation, since declines in insect populations were observed after extreme drought and terrible fires during El Niño 2015–16. Declines in habitat-specialist and disturbance-sensitive bird species and in large-frugivorous mammals were also observed in Amazonian burned forests, while temporary extirpation of more than 100 lowland butterfly species occurred at a burned forest site in Borneo. In seasonally dry tropical forests, which are more drought tolerant, researchers found that El Niño induced drought increased seedling mortality. In a research published in October 2022, researchers studied seasonally dry tropical forests in a national park in Chiang Mai in Thailand for 7 years and observed that El Niño increased seedling mortality even in seasonally dry tropical forests and may impact entire forests in long run.
== Contribution to radioactivity of reprocessed uranium == The half-life of 238U is about 190 times as long as that of 236U; therefore, 236U has about 190 times as much specific activity. Thus, in reprocessed uranium with 0.5% 236U, the 236U and 238U will produce about the same level of radioactivity. (235U contributes only a few percent.) The ratio is less than 190 when the decay products of each are included. The decay chain of uranium-238 to uranium-234 and eventually lead-206 involves emission of eight alpha particles in a time (hundreds of thousands of years) short compared to the half-life of 238U; so a sample of 238U in equilibrium with its decay products (as in natural uranium ore) has eight times the alpha activity of 238U alone. Even purified natural uranium where the post-uranium decay products have been removed, contains an equilibrium quantity of 234U and therefore about twice the alpha activity of pure 238U. Enrichment to increase 235U content will increase 234U to an even greater degree, and roughly half of this 234U will survive in the spent fuel. On the other hand, 236U decays to thorium-232 which has a half-life of 14 billion years, much longer than its own; so its decay chain effectively stops after one step even at long timescales; and the fact that it is an alpha decay means the external exposure hazard is negligible compared to the natural isotopes.
Sources: en.wikipedia.org
It is described as a single molecule that acts at three receptors: the glucose-dependent insulinotropic polypeptide receptor, the glucagon-like peptide-1 receptor, and the glucagon receptor. This triple activity distinguishes it from agents that target one or two of these pathways.
It is characterized in the literature as an investigational agent under clinical study. Approval status depends on jurisdiction, and readers should check current regulatory information rather than assume availability.
The combination is intended to pair appetite-related and glucose-related effects with mechanisms that increase energy expenditure. Whether the combined profile offers advantages over simpler agonists is the subject of ongoing research.
指同一个分子能激活 GIP、GLP-1 和胰高血糖素三类受体。它与只激活一到两种受体的同类分子在设计思路上有所区别。这种设计的目的在于覆盖更多代谢调节通路。